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  • 1.
    Ahlstrand, Inger
    et al.
    ADULT, HHJ, Hälsohögskolan, Högskolan i Jönköping.
    Björk, Mathilda
    Avd. för rehabilitering, HHJ, Hälsohögskolan, Högskolan i Jönköping.
    Thyberg, Ingrid
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Börsbo, Björn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Habilitation in Central County.
    Pain and daily activities in Rheumatoid Arthritis2012In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 34, no 15, p. 1245-1253Article in journal (Refereed)
    Abstract [en]

    Aim: The aim of this study was to describe experiences of pain and its relationship to daily activities in people with rheumatoid arthritis (RA). Method: Seven semi-structured focus group discussions were conducted with 33 men and women of different ages with RA. Data were analysed with content analysis. Results: Pain affected everyday life and may be a barrier to perform valued activities. Regarding the impact of pain on participation and independence, personal factors and the social environment were found to be important. It could be a struggle to find the right activity balance, since it was easy to be overactive, triggering subsequent elevation of pain levels. However, the participants also described activities as a mediator of pain and a distraction from it. Conclusion: The relationship between pain and daily activities in RA was complex. Pain as an impairment was expressed to be related to activity limitations and participation restrictions, as well as to contextual factors. These findings highlight the clinical importance of paying attention to the complexity of pain and its relation to daily activities and participation.

  • 2.
    Ambrosi, Aurelie
    et al.
    Karolinska Institute, Stockholm.
    Salomonsson, Stina
    Karolinska Institute, Stockholm.
    Eliasson, Hakan
    Karolinska Institute, Stockholm.
    Zeffer, Elisabeth
    Karolinska Institute, Stockholm.
    Dzikaite, Vijole
    Karolinska Institute, Stockholm.
    Bergman, Gunnar
    Karolinska Institute, Stockholm.
    Fernlund, Eva
    Skane University Hospital.
    Theander, Elke
    Skane University Hospital.
    Rydberg, Annika
    Umea University Hospital.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Wallberg-Jonsson, Solveig
    Umea University Hospital.
    Ohman, Annika
    Uppsala University.
    Lundstrom, Ulla
    Sahlgrens University Hospital.
    Mellander, Mats
    Sahlgrens University Hospital.
    Winqvist, Ola
    Karolinska Institute, Stockholm.
    Fored, Michael
    Karolinska Institute, Stockholm.
    Ekbom, Anders
    Karolinska Institute, Stockholm.
    Alfredsson, Lars
    Karolinska Institute, Stockholm.
    Kallberg, Henrik
    Karolinska Institute, Stockholm.
    Gadler, Fredrik
    Karolinska Institute, Stockholm.
    Jonzon, Anders
    Uppsala University.
    Sonesson, Sven-Erik
    Karolinska Institute.
    Wahren-Herlenius, Marie
    Karolinska Institute.
    DEVELOPMENT OF HEART BLOCK IN SSA/SSB AUTOANTIBODY-POSITIVE PREGNANCIES IS ASSOCIATED WITH MATERNAL AGE AND DISPLAY A SEASON-OF-BIRTH PATTERN in ANNALS OF THE RHEUMATIC DISEASES, vol 70, issue , pp2011In: ANNALS OF THE RHEUMATIC DISEASES, BMJ Publishing Group , 2011, Vol. 70Conference paper (Refereed)
    Abstract [en]

    n/a

  • 3.
    Ambrosi, Aurelie
    et al.
    Karolinska Institutet, Stockholm.
    Salomonsson, Stina
    Karolinska Institutet, Stockholm.
    Eliasson, Håkan
    Karolinska Institutet, Stockholm.
    Zeffer, Elisabeth
    Karolinska Institutet, Stockholm.
    Skog, Amanda
    Karolinska Institutet, Stockholm.
    Dzikaite, Vijole
    Karolinska Institutet, Stockholm.
    Bergman, Gunnar
    Karolinska Institutet, Stockholm.
    Fernlund, Eva
    Skåne University Hospital, Lund.
    Tingström, Joanna
    Skåne University Hospital, Lund.
    Theander, Elke
    Skåne University Hospital, Malmö.
    Rydberg, Annika
    Umeå University Hospital.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Öhman, Annika
    Uppsala University.
    Lundström, Ulla
    Sahlgrenska University Hospital.
    Mellander, Mats
    Sahlgrenska University Hospital.
    Winqvist, Ola
    Karolinska Institutet, Stockholm.
    Fored, Michael
    Karolinska Institutet, Stockholm.
    Ekbom, Anders
    Karolinska Institutet, Stockholm.
    Alfredsson, Lars
    Institute of Environmental Medicine, Stockholm.
    Källberg, Henrik
    Institute of Environmental Medicine, Stockholm.
    Olsson, Tomas
    Karolinska Institutet, Stockholm.
    Gadler, Fredrik
    Karolinska Institutet, Stockholm.
    Jonzon, Anders
    Sahlgrenska University Hospital, Göteborg.
    Kockum, Ingrid
    Karolinska Institutet, Stockholm.
    Sonesson, Sven-Erik
    Karolinska Institutet, Stockholm.
    Wahren-Herlenius, Marie
    Karolinska Institutet, Stockholm.
    Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no 3, p. 334-340Article in journal (Refereed)
    Abstract [en]

    Objective Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort. less thanbrgreater than less thanbrgreater thanMethods The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies. less thanbrgreater than less thanbrgreater thanResults There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (pandlt;0.05). Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (pandlt;0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies. less thanbrgreater than less thanbrgreater thanConclusion This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

  • 4.
    Arvidsson, Patrik
    et al.
    Örebro University, Sweden; Uppsala University, Sweden .
    Granlund, Mats
    Örebro University, Sweden; Jönköping University, Sweden .
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Thyberg, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Örebro University, Sweden.
    Important aspects of participation and participation restrictions in people with a mild intellectual disability2014In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 36, no 15, p. 1264-1272Article in journal (Refereed)
    Abstract [en]

    Purpose: This study explored a possibility to assess the concepts of participation and participation restrictions in the International Classification of Functioning, Disability and Health (ICF) by combining self-ratings of the perceived importance with the actual performance of different everyday activities in people with a mild intellectual disability. Method: Structured interviews regarding 68 items from the ICF activity/participation domain were conducted (n = 69). The items were ranked by perceived importance, performance and by combined measures. Furthermore, the measures were related to a single question about subjective general well-being. Results: Rankings of performance highlighted about the same items as "important participation", while rankings of low performance addressed quite different items compared with "important participation restriction". Significant correlations were found between subjective general well-being and high performance (r = 0.56), high performance/high importance (important participation) (r = 0.56), low performance (r = -0.56) and low performance/high importance (important participation restriction; r -0.55). Conclusions: The results support the clinical relevance of the ICF and the studied selection of 68 items. Although performance only may sometimes be a relevant aspect, knowledge about the relationship between the perceived importance and the actual performance is essential for clinical interventions and for research aiming to understand specific needs regarding participation.

  • 5.
    Barns, Angela
    et al.
    Curtin University, Perth, Western Australia, Australia.
    Svanholm, Frida
    Linköping University, Department of Medical and Health Sciences.
    Kjellberg, Anette
    Linköping University, Department of Social and Welfare Studies, Division of Occupational Therapy. Linköping University, Faculty of Medicine and Health Sciences.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center. Curtin University, Perth, Western Australia, Australia.
    Living in the present: Women's everyday experiences of living with rheumatoid arthritis2015In: SAGE Open, ISSN 2158-2440, E-ISSN 2158-2440, Vol. 5, no 4, p. 1-13Article in journal (Refereed)
    Abstract [en]

    This article presents the findings from a qualitative research project exploring eight women’s experiences of living with rheumatoid arthritis (RA). Through semistructured interviews, the women provided insights into the physical, emotional, and social impacts of RA and the “work” involved in negotiating its influence in the everyday life. In narrating their experiences of adapting to RA, the women express a common desire for “normalcy,” to return to a time and space before the disruption of RA. The women’s accounts also emphasized the interrelatedness between bodily experience and constructions of self, highlighting the corporeal nature of RA and the constant shaping and reshaping of personal meanings and values.

  • 6.
    Björk, Mathilda
    et al.
    Avd. för rehabilitering, HHJ, Hälsohögskolan, Högskolan i Jönköping.
    Trupin, L.
    University of California, San Francisco.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Katz, P.
    University of California, San Francisco.
    Yelin, E.
    University of California, San Francisco.
    Differences in activity limitation, pain intensity, and global health in patients with rheumatoid arthritis in Sweden and the USA: a 5-year follow-up2011In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 40, no 6, p. 428-432Article in journal (Refereed)
    Abstract [en]

    Objective: In this study we compared activity limitations, pain intensity, and global health in patients with rheumatoid arthritis (RA) in Sweden and the USA and aimed to determine whether nationality is associated with these outcomes. Methods: We used longitudinal data from the Swedish TIRA project (n = 149) and the University of California, San Francisco (UCSF) RA panel study (n = 85). Data were collected annually concerning use of medications [disease-modifying anti-rheumatic drugs (DMARDs), biologics, and corticosteroids], morning stiffness, number of swollen joints, and number of painful joints. Three self-reported outcome measures were examined: pain intensity measured on a 0-100 visual analogue scale (VAS), activity limitation according to the Health Assessment Questionnaire (HAQ), and global health. To analyse the data, the Students t-test, the chi(2)-test, and the generalized estimating equation (GEE) method were used. Results: Nationality was significantly related to HAQ score and pain intensity, even after adjustment for covariates. The patients in the TIRA cohort reported a lower HAQ score and a higher pain intensity than the patients in the UCSF cohort. Nationality was not related to global health. Conclusion: Patients with RA should be assessed with awareness of the psychosocial and cultural context because disability seems to be affected by nationality. Further knowledge to clarify how a multinational setting affects disability could improve the translation of interventions for patients with RA across nationalities.

  • 7.
    Blomgran, Robert
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Brodin Patcha, Veronika
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Bergström, Ida
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Lerm, Maria
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Stendahl, Olle
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
    Sarndahl, Eva
    University of Örebro.
    Common Genetic Variations in the NALP3 Inflammasome Are Associated with Delayed Apoptosis of Human Neutrophils2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 3Article in journal (Refereed)
    Abstract [en]

    Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. less thanbrgreater than less thanbrgreater thanMethods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response. less thanbrgreater than less thanbrgreater thanConclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.

  • 8.
    Bolin, Karin
    et al.
    Uppsala University, Sweden .
    Sandling, Johanna K.
    Uppsala University, Sweden Uppsala University, Sweden .
    Zickert, Agneta
    Karolinska University Hospital, Sweden Karolinska Institute, Sweden .
    Jonsen, Andreas
    Lund University, Sweden .
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Svenungsson, Elisabet
    Karolinska University Hospital, Sweden Karolinska Institute, Sweden .
    Bengtsson, Anders A.
    Lund University, Sweden .
    Eloranta, Maija-Leena
    Uppsala University, Sweden .
    Ronnblom, Lars
    Uppsala University, Sweden Uppsala University, Sweden .
    Syvanen, Ann-Christine
    Uppsala University, Sweden Uppsala University, Sweden .
    Gunnarsson, Iva
    Karolinska University Hospital, Sweden Karolinska Institute, Sweden .
    Nordmark, Gunnel
    Uppsala University, Sweden .
    Association of STAT4 Polymorphism with Severe Renal Insufficiency in Lupus Nephritis2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, p. 84450-Article in journal (Refereed)
    Abstract [en]

    Lupus nephritis is a cause of significant morbidity in systemic lupus erythematosus (SLE) and its genetic background has not been completely clarified. The aim of this investigation was to analyze single nucleotide polymorphisms (SNPs) for association with lupus nephritis, its severe form proliferative nephritis and renal outcome, in two Swedish cohorts. Cohort I (n = 567 SLE cases, n = 512 controls) was previously genotyped for 5676 SNPs and cohort II (n = 145 SLE cases, n = 619 controls) was genotyped for SNPs in STAT4, IRF5, TNIP1 and BLK. Case-control and case-only association analyses for patients with lupus nephritis, proliferative nephritis and severe renal insufficiency were performed. In the case-control analysis of cohort I, four highly linked SNPs in STAT4 were associated with lupus nephritis with genome wide significance with p = 3.7x10(-9), OR 2.20 for the best SNP rs11889341. Strong signals of association between IRF5 and an HLA-DR3 SNP marker were also detected in the lupus nephritis case versus healthy control analysis (pless than0.0001). An additional six genes showed an association with lupus nephritis with pless than0.001 (PMS2, TNIP1, CARD11, ITGAM, BLK and IRAK1). In the case-only meta-analysis of the two cohorts, the STAT4 SNP rs7582694 was associated with severe renal insufficiency with p = 1.6x10(-3) and OR 2.22. We conclude that genetic variations in STAT4 predispose to lupus nephritis and a worse outcome with severe renal insufficiency.

  • 9.
    Boström, E A
    et al.
    University of Gothenburg.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Kechagias, Stergios
    Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Bokarewa, M I
    University of Gothenburg.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Resistin is Associated with Breach of Tolerance and Anti-nuclear Antibodies in Patients with Hepatobiliary Inflammation2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, no 5, p. 463-470Article in journal (Refereed)
    Abstract [en]

    Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohns disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P andlt; 0.001) and PSC (P andlt; 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P andlt; 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.

  • 10.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Sinnescentrum, Pain and Rehabilitation Centre.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Timpka, Toomas
    Linköping University, Department of Medical and Health Sciences, Division of Preventive and Social Medicine and Public Health Science.
    Prognostic rule generation controlling for treatment in early rheumatoid arthritis2009Conference paper (Other academic)
  • 11.
    Ellegård, Rada
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Crisci, Elisa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Burgener, Adam
    University of Manitoba, Winnipeg, Canada; Public Health Agency of Canada, Winnipeg, Canada.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Birse, Kenzie
    University of Manitoba, Winnipeg, Canada; Public Health Agency of Canada, Winnipeg, Canada.
    Westmacott, Garrett
    Public Health Agency of Canada, Winnipeg, Canada.
    Hinkula, Jorma
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Lifson, Jeffrey D.
    Leidos Biomedical Research, Inc., Frederick, MD, USA.
    Larsson, Marie
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Health Sciences.
    Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR32014In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 193, no 9, p. 4590-4601Article in journal (Refereed)
    Abstract [en]

    Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-beta, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1 beta, IL-6, and TNF-alpha, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-kappa B pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.

  • 12.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Sweden.
    Rönnblom, Lars
    Uppsala University, Sweden.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Association of Serum C-Reactive Protein Levels With Lupus Disease Activity in the Absence of Measurable Interferon-α and a C-Reactive Protein Gene Variant2014In: Arthritis & rheumatology (Hoboken, N.J.), ISSN 2326-5191, Vol. 66, no 6, p. 1568-1573Article in journal (Refereed)
    Abstract [en]

    Objectives: The type I interferon (IFN) system is important in the pathogenesis of systemic lupus erythematosus (SLE). We previously demonstrated an inhibitory effect of IFNα on interleukin 6 (IL-6) induced C-reactive protein (CRP) in vitro, hypothetically explaining the poor correlation between disease activity and CRP levels in SLE. Herein we investigated disease activity, IL-6 and CRP in relation to a CRP gene polymorphism and IFN.

    Methods: Sera from 155 SLE patients and 100 controls were analyzed for CRP. Patients were genotyped for a CRP single nucleotide polymorphism (rs1205) associated with low CRP levels. Serum IFNα and IL-6 was quantified by immunoassays. Clinical disease activity was assessed by SLE disease activity index 2000 (SLEDAI-2K).

    Results: CRP levels were increased in SLE patients compared to controls, but were not associated with SLEDAI-2K or IL-6 levels. However, exclusion of patients carrying at least one rs1205 minor allele revealed an association between disease activity and CRP levels (p=0.005). We found a strong association between disease activity and CRP levels (p<0.0005) when patients with measurable IFNα as well as the minor allele of rs1205 where excluded from the analysis. Similarly, when patients with raised IFNα and/or the rs1205 polymorphism were excluded, IL-6 associated with CRP levels.

    Conclusions: The present study demonstrates that serum IFNα as well as CRP genotype affects the CRP response in SLE patients. Lack of correlation between serum levels of CRP and disease activity could therefore be explained by activation of the type I IFN system and polymorphisms in the CRP gene. © 2014 American College of Rheumatology.

  • 13.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Limited Value of Soluble Urokinase Plasminogen Activator Receptor As a Disease Activity Marker in Patients with Systemic Lupus Erythematosus in ARTHRITIS AND RHEUMATISM, vol 63, issue 10, pp S556-S5572011In: ARTHRITIS AND RHEUMATISM, Wiley-Blackwell , 2011, Vol. 63, no 10, p. S556-S557Conference paper (Refereed)
    Abstract [en]

    n/a

  • 14.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Soluble urokinase plasminogen activator receptor levels reflect organ damage in systemic lupus erythematosus2013In: Translational Research: The Journal of Laboratory and Clinical Medicine, ISSN 1931-5244, E-ISSN 1878-1810, Vol. 162, no 5, p. 287-296Article in journal (Refereed)
    Abstract [en]

    Assessments of disease activity and organ damage in systemic lupus erythematosus (SLE) remain challenging because of the lack of reliable biomarkers and disease heterogeneity. Ongoing inflammation can be difficult to distinguish from permanent organ damage caused by previous flare-ups or medication side effects. Circulating soluble urokinase plasminogen activator receptor (suPAR) has emerged as a potential marker of inflammation and disease severity, and an outcome predictor in several disparate conditions. This study was done to evaluate suPAR as a marker of disease activity and organ damage in SLE. Sera from 100 healthy donors- and 198 patients with SLE fulfilling the 1982 American College of Rheumatology classification criteria and/or the Fries criteria were analyzed for suPAR by enzyme immunoassay. Eighteen patients with varying degree of disease activity were monitored longitudinally. Disease activity was assessed by the SLE disease activity index 2000 and the physicians global assessment. Organ damage was evaluated by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index (SDI). Compared with healthy control subjects, serum suPAR levels were elevated significantly in patients with SLE. No association was recorded regarding suPAR levels and SLE disease activity in cross-sectional or consecutive samples. However, a strong association was observed between suPAR and SDI (P andlt; 0.0005). Considering distinct SDI domains, renal, neuropsychiatric, ocular, skin, and peripheral vascular damage had.a significant effect on suPAR levels. This study is the first to demonstrate an association between serum suPAR and irreversible organ damage in SLE. Further studies are warranted to evaluate suPAR and other biomarkers as predictors of evolving organ damage.

  • 15.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Jacobs, Claudia
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Johansson, Karl-Erik
    Linköping University, Department of Clinical and Experimental Medicine, Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery UHL.
    Remission of arthritis after esophagectomy in three patients with severe achalasia2013In: Diseases of the esophagus, ISSN 1120-8694, E-ISSN 1442-2050, Vol. 26, no 3, p. 226-230Article in journal (Refereed)
    Abstract [en]

    In the 1960s and 1970s, intestinal bypass surgery was performed to treat patients with extreme obesity. However, this is now done with great restriction due to the risk of complications, for instance, polyarthritis. An association between severe achalasia and arthritis has also been described, but very few articles on this topic are cited in PubMed, and most of the published case reports are old. In this article, we present a retrospective case series of three patients with severe achalasia and arthritis from the departments of rheumatology and surgery at a university hospital. The complaints from the esophagus as well as arthritis were resolved after esophagectomy and esophageal reconstruction. We conclude that severe achalasia can be associated with arthritis, and both can be cured by esophageal reconstruction. Thus, we want to remind of this rare, but probably largely unrecognized, association between achalasia and joint disease.

  • 16.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Jacobs, Claudia
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    A patient with Phenotype of Adult-onset Still Disease, But a Genotype Typical of Cryopyrin-associated Periodic Fever Syndrome2013In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 40, no 9, p. 1632-1633Article in journal (Other academic)
  • 17.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Sandell, Christina
    Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Backteman, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    B Cell Abnormalities in Wegeners Granulomatosis and Microscopic Polyangiitis: Role of CD25+-expressing B Cells2010In: JOURNAL OF RHEUMATOLOGY, ISSN 0315-162X, Vol. 37, no 10, p. 2086-2095Article in journal (Refereed)
    Abstract [en]

    Objective. The use of rituximab in vasculitis has increased interest in B cell biology. A subpopulalion of B cells expressing CD25 shows antigen-presenting properties and may have regulatory functions. We assessed subpopulations of B cell maturation (Bm) and markers related to activity and antigen presentation, and related the findings to disease activity. Methods. Multiparameter flow cytometry was used to assess numbers and proportions of circulating lymphocytes from 34 patients with vasculitis (16 remission, 18 active) and 20 controls. Results. Active vasculitis samples showed decreased proportions of Bm1 (7.8% vs 11%; p = 0.041), Bm2 (0.2% vs 0.7%; p = 0.002), and Bm3/Bm4 (0.1% vs 0.3%; p = 0.006), compared with controls; Bm2 cells were the most frequently occurring B cells but they were not significantly different in active vasculitis (74% vs 62%; p = 0.083). In patients with remission the proportion of CD25+ B cells was increased compared to controls (48% vs 29%, respectively; p = 0.006) and also compared to active vasculitis (23%; p = 0.006). The proportion of CD86+ B cells was also increased (31%) compared to active vasculitis (8%; p = 0.001), and to controls (6%; p = 0.0003). In multivariate analysis. Bm2 cells and CD25+27- B cells were independently influencing the patient group. Conclusion. In active vasculitis, a lower proportion of Bm I cells may indicate activated B cells. Patients in remission had higher proportions of CD25+ (a-chain of interleukin 2 receptor) and CD86+ (costimulatory molecule) B cells. We suggest that these B cells may have a regulatory role, or alternatively may result from previous treatment.

  • 18.
    Forsgren, Mikael
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Bengtsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Sören, Birgitta
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. Linköping University, Faculty of Health Sciences.
    Brandejsky, Vaclav
    Depts Clinical Research and Radiology, University Bern, Bern, Switzerland.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    31P MRS as a Potential Biomarker for Fibromyalgia2012In: Proceedings of the 20th Annaal Meeting & Exhibition, 5-11 May, Melbourne, Australia, 2012, p. 1493-1493Conference paper (Refereed)
    Abstract [en]

    Major clinical symptoms in fibromyalgia (FM) are muscle pain, stiffness and fatigue. Studies have shown reduced voluntary strength and exercise capacity, lower endurance and more muscular pain even at low workload. An impaired muscle energy metabolism has therefore been proposed as a result of the disease. An earlier study using magnetic resonance spectroscopy (MRS) showed that at maximal dynamic and static contractions the concentration of inorganic phosphate was lower in FM [1]. A decrease in ATP, ADP and PCr and an increase in AMP and creatine was found in FM biopsies [2]. The purpose of this study was to non-invasively analyze the quantitative content of  phosphagens in the resting muscle in FM in comparison to healthy controls using 31P MRS of the quadriceps muscle.

  • 19.
    Forsgren, Mikael
    et al.
    Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Weber, Patrick
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Janzén, David
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Pena, José
    Linköping University, Department of Computer and Information Science, Database and information techniques. Linköping University, The Institute of Technology.
    Cedersund, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Bayesian mixed-effect modeling of contrast agent data for decision-support when diagnosing diffuse liver disease2012Conference paper (Other academic)
  • 20.
    Frodlund, Martina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Dahlström, Örjan
    Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register2013In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 3, p. 1-8Article in journal (Refereed)
    Abstract [en]

    Objective Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes.

    Design Observational cohort study.

    Setting One university hospital rheumatology unit in Sweden.

    Participants The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ≥4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ≥2 typical organ manifestations at the time of diagnosis (Fries’ criteria).

    Outcome measures The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique).

    Results 54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries’ criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 (‘immunological disorder’). S-ANA was inversely associated with arthritis, ‘immunological disorder’ and signs of organ damage.

    Conclusions H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with ‘immunological disorder’ according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage.

  • 21.
    Gerdle, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Forsgren, Mikael
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Bengtsson, Ann
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Sören, B.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Karlsson, Anette
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Health Sciences.
    Brandejsky, Vaslav
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lund, Eva
    Linköping University, Department of Medical and Health Sciences, Radiation Physics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Lundberg, Peter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Östergötlands Läns Landsting, Center for Diagnostics, Department of Radiology in Linköping.
    Decreased muscle concentrations of ATP and PCR in the quadriceps muscle of fibromyalgia patients – A 31P-MRS study2013In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 17, no 8, p. 1205-1215Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND METHODS:

    Fibromyalgia (FMS) has a prevalence of approximately 2% in the population. Central alterations have been described in FMS, but there is not consensus with respect to the role of peripheral factors for the maintenance of FMS. 31P magnetic resonance spectroscopy (31P-MRS) has been used to investigate the metabolism of phosphagens in muscles of FMS patients, but the results in the literature are not in consensus. The aim was to investigate the quantitative content of phosphagens and pH in resting quadriceps muscle of patients with FMS (n = 19) and in healthy controls (Controls; n = 14) using (31) P-MRS. It was also investigated whether the concentrations of these substances correlated with measures of pain and/or physical capacity.

    RESULTS:

    Significantly lower concentrations of adenosine triphosphate (ATP) and phosphocreatinine (PCr; 28-29% lower) were found in FMS. No significant group differences existed with respect to inorganic phosphate (Pi), Pi/PCr and pH. The quadriceps muscle fat content was significantly higher in FMS than in Controls [FMS: 9.0 ± 0.5% vs. Controls: 6.6 ± 0.6%; (mean ± standard error); P = 0.005]. FMS had significantly lower hand and leg capacity according to specific physical test, but there were no group differences in body mass index, subjective activity level and in aerobic fitness. In FMS, the specific physical capacity in the leg and the hand correlated positively with the concentrations of ATP and PCr; no significant correlations were found with pain intensities.

    CONCLUSIONS:

    Alterations in intramuscular ATP, PCr and fat content in FMS probably reflect a combination of inactivity related to pain and dysfunction of muscle mitochondria.

  • 22.
    Haldorsen, K.
    et al.
    University of Bergen, Norway University of Bergen, Norway .
    Appel, S.
    University of Bergen, Norway .
    Le Hellard, S.
    University of Bergen, Norway .
    Bruland, O.
    Haukeland Hospital, Norway .
    Brun, J. G.
    Haukeland Hospital, Norway .
    Omdal, R.
    Stavanger University Hospital, Norway .
    Kristjansdottir, G.
    Uppsala University, Sweden .
    Theander, E.
    Lund University, Sweden .
    Fernandes, C. P. D.
    University of Bergen, Norway .
    Kvarnstrom, M.
    Karolinska Institute, Sweden .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Ronnblom, L.
    Uppsala University, Sweden .
    Herlenius, M. W.
    Karolinska Institute, Sweden .
    Nordmark, G.
    Uppsala University, Sweden .
    Jonsson, R.
    University of Bergen, Norway Haukeland Hospital, Norway .
    Bolstad, A. I.
    University of Bergen, Norway .
    No association of primary Sjogrens syndrome with Fc gamma receptor gene variants2013In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 14, no 4, p. 234-237Article in journal (Refereed)
    Abstract [en]

    The genetic background of primary Sjogrens syndrome (pSS) is partly shared with systemic lupus erythematosus (SLE). Immunoglobulin G Fc receptors are important for clearance of immune complexes. Fcg receptor variants and gene deletion have been found to confer SLE risk. In this study, four Fc gamma receptor single-nucleotide polymorphisms (SNPs) and one copy number variation (CNV) were studied. Swedish and Norwegian pSS patients (N = 527) and controls (N = 528) were genotyped for the Fc gamma receptor gene variant FCGR2A H131R (rs1801274) by the Illumina GoldenGate assay. FCGR3A F158V (rs396991) was analysed in 488 patients and 485 controls, FCGR3B rs447536 was analysed in 471 patients and 467 controls, and FCGR3B rs448740 was analysed in 478 cases and 455 controls, using TaqMan SNP genotyping assays. FCGR3B CNV was analysed in 124 patients and 139 controls using a TaqMan copy number assay. None of the SNPs showed any association with pSS. Also, no FCGR3B CNV association was detected. The lack of association of pSS with Fc gamma receptor gene variants indicates that defective immune complex clearance may not be as important in pSS pathogenesis as in SLE, and may point to important differences between SLE and pSS.

  • 23.
    Hallert, Eva
    et al.
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Björk, Mathilda
    School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Dahlström, Örjan
    Linköping University, The Swedish Institute for Disability Research. Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Disease activity and disability in women and men with early rheumatoid arthritis: An 8-year follow-up of the Swedish TIRA project2012In: Arthritis Care and Research, ISSN 0893-7524, E-ISSN 1529-0123, Vol. 64, no 8, p. 1101-1107Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To compare women and men regarding course of disease activity and disability over 8 years from diagnosis of recent onset rheumatoid arthritis (RA). PATIENTS AND METHODS: 149 patients were followed for 8 years from RA diagnosis (1996-98) regarding 28-joint count disease activity score (DAS28), pain (visual analogue scale, VAS), grip force, Grip Ability Test (GAT), Signals of Functional Impairment (SOFI hand, upper/lower extremity), walking speed, activity limitation (Health Assessment Questionnaire, HAQ) and prescribed disease-modifying anti-rheumatic drugs (DMARDs). RESULTS: Disease activity pattern over time was similar in women and men, showing improvement during the first year and thereafter a stable situation during 6 years. However, at the 7- and 8-year follow-ups deterioration was seen with a less favourable course in women. HAQ did not differ between sexes at diagnosis, but at all follow-ups women had significantly higher scores than men. Women also had lower grip force and lower walking speed, but higher upper extremity mobility. DMARD prescription was similar for both sexes. Over eight years, disease duration, sex, biologics, grip force, SOFI-hand and pain intensity together explained 43% of the variation in DAS, while grip force, SOFI-lower, GAT and pain intensity could together explain 55% of variations in HAQ. CONCLUSIONS: Disease activity was fairly well managed, but disability gradually deteriorated. Despite similar medication, women had more disability than men. The discrepancy between disease activity and disability indicates unmet needs for multi-professional interventions to prevent progressing disability and patients at risk for disability need to be identified early in the process. © 2012 by the American College of Rheumatology.

  • 24.
    Hallert, Eva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Kalkan, Almina
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Rahmqvist, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Allergy Center.
    Changes in sociodemographic characteristics at baseline in two Swedish cohorts of patients with early rheumatoid arthritis diagnosed 1996-98 and 2006-092015In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 44, no 2, p. 100-105Article in journal (Refereed)
    Abstract [en]

    Objectives: To compare baseline sociodemographic characteristics in two rheumatoid arthritis (RA) cohorts enrolled 10 years apart, and to examine differences with respect to the general population. Method: Clinical and sociodemographic data were collected in 320 early RA patients during 1996-98 (TIRA-1) and 467 patients in 2006-09 (TIRA-2). Multivariate logistic regression tests were performed and intercohort comparisons were related to general population data, obtained from official databases. Results: TIRA-2 patients were older than TIRA-1 (58 vs. 56 years). Women (both cohorts, 67%) were younger than men in TIRA-1 (55 vs. 59 years) and in TIRA-2 (57 vs. 61 years). Disease activity was similar but TIRA-2 women scored worse pain and worse on the HAQ. Approximately 73% were cohabiting, in both cohorts and in the general population. Education was higher in TIRA-2 than in TIRA-2 but still lower than in the general population. Women had consistently higher education than men. Education was associated with age, younger patients having higher education. In both cohorts, lower education was associated with increased disability pension and increased sick leave. Sick leave was lower in TIRA-2 than in TIRA-1 (37% vs. 50%) but disability pension was higher (16% vs. 10%). In TIRA-1, 9% of women had disability pension compared with 17% in TIRA-2. A similar decrease in sick leave and an increase in disability pension were also seen in the general population. Older age and a higher HAQ score were associated with increased sick leave and being in the TIRA-2 cohort was associated with decreased sick leave. Conclusions: TIRA-2 patients were slightly older, better educated, had lower sick leave and higher disability pension than those in TIRA-1. Similar changes were seen simultaneously in the general population. Belonging to the TIRA-2 cohort was associated with decreased sick leave, indicating that societal changes are of importance.

  • 25.
    Hallert, Eva
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Kalkan, Almina
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Bernfort, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Health Sciences.
    Early rheumatoid arthritis 6 years after diagnosis is still associated with high direct costs and increasing loss of productivity: the Swedish TIRA project2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    Objectives: To calculate total costs over 6 years after diagnosis of early rheumatoid arthritis (RA).

    Method: In the longitudinal prospective multicentre TIRA study, 239 patients from seven units, diagnosed in 1996–98, reported regularly on health-care utilization and the number of days lost from work. Costs were obtained from official databases and calculated using unit costs (Swedish kronor, SEK) from 2001. Indirect costs were calculated using the human capital approach (HCA). Costs were inflation adjusted to Euro June 2012, using the Swedish Consumer Price Index and the exchange rate of June 2012. Statistical analyses were based on linear mixed models (LMMs) for changes over time.

    Results: The mean total cost per patient was EUR 14 768 in year 1, increasing to EUR 18 438 in year 6. Outpatient visits and hospitalization decreased but costs for surgery increased from EUR 92/patient in year 1 to EUR 444/patient in year 6. Drug costs increased from EUR 429/patient to EUR 2214/patient, mainly because of the introduction of biologics. In year 1, drugs made up for 10% of direct costs, and increased to 49% in year 6. Sick leave decreased during the first years but disability pensions increased, resulting in unchanged indirect costs. Over the following years, disability pensions increased further and indirect costs increased from EUR 10 284 in year 1 to EUR 13 874 in year 6. LMM analyses showed that indirect costs were unchanged whereas direct costs, after an initial fall, increased over the following years, leading to increasing total costs.

    Conclusions: In the 6 years after diagnosis of early RA, drug costs were partially offset by decreasing outpatient visits but indirect costs remained unchanged and total costs increased.

     

  • 26.
    Hallert, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Rehabilitation Center. Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics.
    Husberg, Magnus
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    28-joint count disease activity score at 3 months after diagnosis of early rheumatoid arthritis is strongly associated with direct and indirect costs over the following 4 years: the Swedish TIRA project2011In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 50, no 7, p. 1259-1267Article in journal (Refereed)
    Abstract [en]

    Methods. Three-hundred and twenty patients with early (1 year) RA were assessed at regular intervals. Clinical and laboratory data were collected and patients reported health-care utilization and number of days lost from work. At 3-month follow-up, patients were divided into two groups according to disease activity, using DAS-28 with a cut-off level at 3.2. Direct and indirect costs and EuroQol-5D over the following 4 years were compared between the groups. Multivariate regression models were used to control for possible covariates. Results. Three months after diagnosis, a DAS-28 level of epsilon 3.2 was associated with high direct and indirect costs over the following 4 years. Patients with DAS-28 epsilon 3.2 at 3-month follow-up had more visits to physician, physiotherapist, occupational therapist and nurse, higher drug costs, more days in hospital and more extensive surgery compared with patients with 3-month DAS-28 less than 3.2. Number of days lost from work due to sick leave and permanent work disability was also higher in this group. The effect of disease activity on health-related quality of life was highly significant. In regression models, DAS-28 at 3-month follow-up was significantly associated with costs over the following years. Conclusions. Three months after diagnosis, DAS-28 is an important prognostic marker regarding health-care utilization and costs. Achieving remission or low disease activity 3 months after diagnosis is likely to decrease morbidity, increase quality of life and save costs for the patient and for society over the following years.

  • 27.
    Hammond, Alison
    et al.
    University of Salford, England.
    Tyson, Sarah
    University of Manchester, England.
    Prior, Yeliz
    University of Salford, England.
    Hawkins, Ruth
    Derby Branch National Rheumatoid Arthrit Soc Patient, England.
    Tennant, Alan
    Swiss Parapleg Research, Switzerland; University of Leeds, England.
    Nordenskiold, Ulla
    University of Gothenburg, Sweden.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Sandqvist, Gunnel
    Lund University, Sweden.
    Cederlund, Ragnhild
    Lund University, Sweden.
    Linguistic validation and cultural adaptation of an English version of the Evaluation of Daily Activity Questionnaire in rheumatoid arthritis2014In: Health and Quality of Life Outcomes, ISSN 1477-7525, E-ISSN 1477-7525, Vol. 12, no 143Article in journal (Refereed)
    Abstract [en]

    Background: To linguistically validate and culturally adapt the Evaluation of Daily Activity Questionnaire (EDAQ) for use in rheumatoid arthritis (RA) from Swedish to British English. The EDAQ is a patient reported outcome measure of daily activity ability. It includes 11 activity domains (Eating and Drinking; Personal Care; Dressing; Bathing; Cooking; Moving Indoors; House Cleaning; Laundry; Moving and Transfers; Communication; Moving Outdoors) and was developed for use in rheumatoid arthritis (RA). Methods: The EDAQ was translated from Swedish to English using standard methods. Activity diaries, cognitive debriefing interviews and focus groups were completed with people with RA to: generate new culturally applicable items; identify important items in the Swedish version to retain in the English version; and develop the English EDAQ based on their views of content and layout. Content validity was established by linking the EDAQ to the International Classification of Functioning RA Core Set. Results: The English EDAQ translation was harmonized with the Swedish version to ensure equivalence of meaning. Sixty-one people with RA participated. 156 activities were identified from 31 activity diaries and included in a draft English EDAQ. Following interviews (n = 20) and four focus groups, 138 activities were retained and three additional domains added (Gardening/Household Maintenance; Caring; and Leisure/Social Activities). Most ICF RA Core Set activities are in the EDAQ. Conclusions: The English EDAQ is a detailed self-report measure of ability in RA with good content validity.

  • 28.
    Isine Bolstad, Anne
    et al.
    University of Bergen.
    Le Hellard, Stephanie
    University of Bergen.
    Kristjansdottir, Gudlaug
    Uppsala University.
    Vasaitis, Lilian
    Uppsala University.
    Kvarnstrom, Marika
    Karolinska Institute.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Joar Auglaend Johnsen, Svein
    Stavanger University Hospital.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Omdal, Roald
    Stavanger University Hospital.
    Brun, Johan G
    University of Bergen.
    Wahren-Herlenius, Marie
    Karolinska Institute.
    Theander, Elke
    Lund University.
    Syvanen, Ann-Christine
    Uppsala University.
    Ronnblom, Lars
    Uppsala University.
    Nordmark, Gunnel
    Uppsala University.
    Jonsson, Roland
    University of Bergen.
    Association between genetic variants in the tumour necrosis factor/lymphotoxin alpha/lymphotoxin beta locus and primary Sjogrens syndrome in Scandinavian samples2012In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, no 6, p. 981-988Article in journal (Refereed)
    Abstract [en]

    Objectives Lymphotoxin beta (LTB) has been found to be upregulated in salivary glands of patients with primary Sjogrens syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin alpha (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS. less thanbrgreater than less thanbrgreater thanMethods 527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing. less thanbrgreater than less thanbrgreater thanResults Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS. less thanbrgreater than less thanbrgreater thanConclusions A strong association was found between several SNP in the LTA/LTB/TNF alpha locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.

  • 29.
    Kanmert, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology. Linköping University, The Institute of Technology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Almroth, Gunnel
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Sensor Science and Molecular Physics . Linköping University, The Institute of Technology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    IgG Rheumatoid Factor Against the Four Human Fc-gamma Subclasses in Early Rheumatoid Arthritis (the Swedish TIRA Project)Manuscript (preprint) (Other academic)
    Abstract [en]

    Rheumatoid factor (RF), i.e. a family of autoantibodies against the Fc part of IgG, is an important seromarker of rheumatoid arthritis (RA). Traditional particle agglutination without disclosing the antibody isotype remains the predominating diagnostic method in clinical routine. Although IgG-RF attracts pathogenic interest, its detection remains technically challenging. The present study aimed at developing a set of tests identifying IgG-RFs directed against the four IgG subclasses. IgG-RF against either subclass of human IgG-Fc were analyzed with four novel enzyme-linked immunosorbent assays (ELISAs) utilizing four recombinant human Fc-gamma fragments (hIgG1-4) as sources of antigen. Sera from 40 patients with recent-onset RA (20 seropositive and 20 seronegative by IgM-RF and IgA-RF-isotype specific ELISA) were analyzed. Sera from 20 healthy blood donors served as reference. Among the IgM-/IgA-RF positive RA-sera, IgG-RF was found directed against hIgG1, hIgG4, and most notably, with strikingly high reactivity against hIgG2, but not hIgG3. Significant correlations were seen between IgG-RF against hIgG2-Fc and IgA-RF (r = 0.513) and IgM-RF (r = 0.736) levels. Further prospective studies are warranted to elucidate any correlation to disease course and outcome.

  • 30.
    Kanmert, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Almroth, Gunnel
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    IgG Rheumatoid Factors Against the Four Human Fc-gamma Subclasses in Early Rheumatoid Arthritis (The Swedish TIRA Project)2012In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 75, no 1, p. 115-119Article in journal (Refereed)
    Abstract [en]

    Rheumatoid factor (RF), i.e. a family of autoantibodies against the Fc part of IgG, is an important seromarker of rheumatoid arthritis (RA). Traditional particle agglutination without disclosing the antibody isotype remains the predominating diagnostic method in clinical routine. Although IgG-RF attracts pathogenic interest, its detection remains technically challenging. The present study aimed at developing a set of tests identifying IgG-RFs directed against the four IgG subclasses. IgG-RF against either subclass of human IgG-Fc were analysed with four novel enzyme-linked immunosorbent assays (ELISAs) utilizing four recombinant human Fc-gamma fragments (hIgG14) as sources of antigen. Sera from 40 patients with recent onset RA (20 seropositive and 20 seronegative by IgM-RF and IgA-RF-isotype-specific ELISA) were analysed. Sera from 20 healthy blood donors served as reference. Among the IgM-/IgA-RF-positive RA-sera, IgG-RF was found directed against hIgG1 and hIgG2, but not against hIgG3 or hIgG4. Significant correlations were seen between IgG-RF against hIgG2-Fc and IgM-RF (r = 0.666) levels. Further prospective studies are warranted to elucidate any correlation to disease course and outcome.

  • 31.
    Kastbom, Alf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Cöster, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Ärlestig, Lisbeth
    Umeå University, Sweden .
    Chatzidionysiou, Aikaterini
    Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden .
    van Vollenhoven, Ronald F.
    Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden .
    Padyukov, Leonid
    Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden .
    Rantapää-Dahlqvist, Solbritt
    Umeå University, Sweden .
    Saevarsdottir, Saedis
    Karolinska University Hospital and Karolinska Institute, Stockholm, Sweden .
    Influence of FCGR3A genotype on the therapeutic response to rituximab in rheumatoid arthritis: an observational cohort study2012In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 2, no 5Article in journal (Refereed)
    Abstract [en]

    Objectives To determine whether a polymorphism in the Fcγ receptor type IIIA (FCGR3A-F158V), influencing immunoglobulin G binding affinity, relates to the therapeutic efficacy of rituximab in rheumatoid arthritis (RA) patients.

    Design Observational cohort study.

    Setting Three university hospital rheumatology units in Sweden.

    Participants Patients with established RA (n=177; 145 females and 32 males) who started rituximab (Mabthera) as part of routine care.

    Primary outcome measures Response to rituximab therapy in relation to FCGR3A genotype, including stratification for sex.

    Results The frequency of responders differed significantly across FCGR3A genotypes (p=0.017 in a 3×2 contingency table). Heterozygous patients showed the highest response rate at 83%, as compared with patients carrying 158FF (68%) or 158VV (56%) (p=0.028 and 0.016, respectively). Among 158VV patients, response rates differed between male and female patients (p=0.036), but not among 158FF or 158VF patients (p=0.72 and 0.46, respectively).

    Conclusions Therapeutic efficacy of rituximab in RA patients is influenced by FCGR3A genotype, with the highest response rates found among heterozygous patients. This may suggest that different rituximab mechanisms of action in RA are optimally balanced in FCGR3A-158VF patients. Similar to the previously described associations with RA susceptibility and disease course, the impact of 158VV on rituximab response may be influenced by sex.

  • 32.
    Kastbom, Alf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Klingberg, E
    University of Gothenburg, Sweden .
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Carlsten, H
    University of Gothenburg, Sweden .
    Forsblad-dElia, H
    University of Gothenburg, Sweden .
    Wesamaa, J
    Örebro University Hospital, Sweden .
    Cedergren, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Söderkvist, P
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
    Genetic variants in CARD8 but not in NLRP3 are associated with ankylosing spondylitis2013In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, no 6, p. 465-468Article in journal (Refereed)
    Abstract [en]

    Objectives: The NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is important for interleukin-1beta (IL-1 beta) processing as part of an innate immune response. Caspase recruitment domain family, member 8 (CARD8) is an inhibitor of nuclear factor kappa B (NF-kappa B) and possibly also a part of the NLRP3 inflammasome. The objective of this study was to evaluate one single nucleotide polymorphism (SNP) in CARD8 and three SNPs in NLRP3 in ankylosing spondylitis (AS) susceptibility and disease phenotype. less thanbrgreater than less thanbrgreater thanMethod: We recruited 492 AS patients from Southern Sweden fulfilling the modified New York criteria for AS, and assessed phenotypic characteristics from medical records and questionnaires. Patients with psoriasis or clinically overt inflammatory bowel disease (IBD) were excluded, as were patients without human leucocyte antigen B27 (HLA-B27). Three NLRP3 SNPs (rs35829419, rs4353135, and rs10733113) and one SNP in CARD8 (rs2043211) were genotyped by commercially available TaqMan assays, and the results compared at genotype and allele levels to those of 793 population-based controls. In a subgroup of the patients (n = 169), faecal calprotectin was assessed as a marker of subclinical intestinal inflammation. less thanbrgreater than less thanbrgreater thanResults: The minor allele (A) of CARD8-C10X (rs2043211) was associated with a decreased risk of AS in a dominant model [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54-0.94, p = 0.012] and at the allelic level (OR 0.81, 95% CI 0.68-0.97, p = 0.02), but was not associated with levels of faecal calprotectin. There was no association regarding NLRP3 SNPs and AS susceptibility, and none of the investigated SNPs were associated with iritis, anti-tumour necrosis factor (anti-TNF) therapy, or peripheral joint involvement. less thanbrgreater than less thanbrgreater thanConclusion: In a Swedish population, the minor allele of CARD8-C10X is associated with a decreased risk of AS, but not with levels of faecal calprotectin or disease phenotype.

  • 33.
    Kienhöfer, D
    et al.
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Hahn, J
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Schubert, I
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Reinwald, C
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Ipseiz, N
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Lang, S C
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Borràs, È Bosch
    Universitat Autònoma de Barcelona, Barcelona, Spain.
    Amann, K
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Barron, A E
    Stanford University, Stanford, USA .
    Hueber, A J
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Agerberth, B
    Karolinska University, Stockholm, Sweden.
    Schett, G
    Universitätsklinikum Erlangen, Erlangen, Germany.
    Hoffmann, M H
    Universitätsklinikum Erlangen, Erlangen, Germany.
    No evidence of pathogenic involvement of cathelicidins in patient cohorts and mouse models of lupus and arthritis2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 12, p. 1-19Article in journal (Refereed)
    Abstract [en]

    Apart from their role in the immune defence against pathogens evidence of a role of antimicrobial peptides (AMPs) in autoimmune diseases has accumulated in the past years. The aim of this project was to examine the functional impact of the human cathelicidin LL-37 and the mouse cathelicidin-related AMP (CRAMP) on the pathogenesis of lupus and arthritis. Serum LL-37 and anti-LL-37 levels were measured by ELISA in healthy donors and patients with Systemic Lupus Erythematosus (SLE) and Rheumatoid arthritis (RA). Pristane-induced lupus was induced in female wild type (WT) and cathelicidin-deficient (CRAMP-/-) mice. Serum levels of anti-Sm/RNP, anti-dsDNA, and anti-histone were determined via ELISA, cytokines in sera and peritoneal lavages were measured via Multiplex. Expression of Interferon I stimulated genes (ISG) was determined by real-time PCR. Collagen-induced arthritis (CIA) was induced in male WT and CRAMP-/- mice and arthritis severity was visually scored and analysed histomorphometrically by OsteoMeasure software. Serum levels of anti-LL-37 were higher in SLE-patients compared to healthy donors or patients with RA. However, no correlation to markers of disease activity or organ involvement was observed. No significant differences of autoantibody or cytokine/chemokine levels, or of expression of ISGs were observed between WT and CRAMP-/- mice after pristane-injection. Furthermore, lung and kidney pathology did not differ in the absence of CRAMP. Incidence and severity of CIA and histological parameters (inflammation, cartilage degradation, and bone erosion) were not different in WT and CRAMP-/- mice. Although cathelicidins are upregulated in mouse models of lupus and arthritis, cathelicidin-deficiency did not persistently affect the diseases. Also in patients with SLE, autoantibodies against cathelicidins did not correlate with disease manifestation. Reactivity against cathelicidins in lupus and arthritis could thus be an epiphenomenon caused by extensive overexpression in blood and affected tissues. In addition, other cationic AMPs could functionally compensate for the deficiency of cathelicidins.

  • 34.
    Kurz, Tino
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Weiner, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    Skoglund, Camilla
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences.
    Basnet, Sandeep
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Health Sciences.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Nephrology.
    A myelopoiesis gene signature during remission in ANCA associated vasculitis does not predict relapses but seems to reflect ongoing prednisolone therapy2014In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 175, no 2, p. 215-226Article in journal (Refereed)
    Abstract [en]

    A myelopoiesis gene signature in circulating leucocytes, exemplified by increased myeloperoxidase (MPO) and proteinase 3 (PR3) mRNA levels, has been reported in patients with active anti-neutrophil cytoplasm antibody associated vasculitis (AAV) and to a lesser extent during remission. We hypothesized that this signature could predict disease relapse. mRNA levels of PR3, MPO, selected myelopoiesis transcription factors (CEBPA, CEBPB, SPIB, SPI1) and microRNAs (miRNAs) from patient and control peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) were analyzed and associated with clinical data. Patients in stable remission had higher mRNA levels for PR3 (PBMCs, PMNs) and MPO (PBMCs). PR3 and SPIB mRNA correlated positively in control but negatively in patient PBMCs. Statistically significant correlations existed between PR3 mRNA and several miRNAs in controls, but not in patients. PR3/MPO mRNA levels were not associated with previous or future relapses but correlated to steroid treatment. Prednisolone doses were negatively linked to SPIB and miR-155-5p, miR-339-5p (PBMCs) and to miR-221, miR-361, miR-505 (PMNs). PR3 mRNA in PBMCs correlated with time since last flare, blood leucocyte count and estimated glomerular filtration rate. Our results show that elevated leucocyte PR3 mRNA levels in AAV patients in remission do not predict relapse. The origin seems multifactorial, but to an important part explainable by prednisolone action. Gene signatures in patients with AAV undergoing steroid treatment should therefore be interpreted accordingly.

  • 35.
    Lessard, Christopher J.
    et al.
    Oklahoma Medical Research Fdn, OK USA .
    Li, He
    Oklahoma Medical Research Fdn, OK USA .
    Adrianto, Indra
    Oklahoma Medical Research Fdn, OK USA .
    Ice, John A.
    Oklahoma Medical Research Fdn, OK USA .
    Rasmussen, Astrid
    Oklahoma Medical Research Fdn, OK USA .
    Grundahl, Kiely M.
    Oklahoma Medical Research Fdn, OK USA .
    Kelly, Jennifer A.
    Oklahoma Medical Research Fdn, OK USA .
    Dozmorov, Mikhail G.
    Oklahoma Medical Research Fdn, OK USA .
    Miceli-Richard, Corinne
    University of Paris 11, France .
    Bowman, Simon
    University Hospital Birmingham, England .
    Lester, Sue
    Queen Elizabeth Hospital, Australia .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Eloranta, Maija-Leena
    Uppsala University, Sweden .
    Brun, Johan G.
    University of Bergen, Norway .
    Goransson, Lasse G.
    Stavanger University Hospital, Norway .
    Harboe, Erna
    Stavanger University Hospital, Norway .
    Guthridge, Joel M.
    Oklahoma Medical Research Fdn, OK USA .
    Kaufman, Kenneth M.
    Cincinnati Childrens Hospital Medical Centre, OH USA .
    Kvarnstrom, Marika
    Karolinska Institute, Sweden .
    Jazebi, Helmi
    Karolinska Institute, Sweden .
    Cunninghame Graham, Deborah S.
    Kings Coll London, England .
    Grandits, Martha E.
    United Medical Specialties, MN USA .
    Nazmul-Hossain, Abu N M.
    University of Colorado, CO USA .
    Patel, Ketan
    University of Minnesota, MN USA .
    Adler, Adam J.
    Oklahoma Medical Research Fdn, OK USA .
    Maier-Moore, Jacen S.
    Oklahoma Medical Research Fdn, OK USA .
    Darise Farris, A
    Oklahoma Medical Research Fdn, OK USA .
    Brennan, Michael T.
    Carolinas Medical Centre, NC USA .
    Lessard, James A.
    Valley Bone and Joint Clin, ND USA .
    Chodosh, James
    Harvard University, MA USA .
    Gopalakrishnan, Rajaram
    University of Minnesota, MN USA .
    Hefner, Kimberly S.
    Hefner Eye Care and Opt Centre, OK USA .
    Houston, Glen D.
    University of Oklahoma, OK USA .
    Huang, Andrew J W.
    Washington University, MO USA .
    Hughes, Pamela J.
    University of Oklahoma, OK USA .
    Lewis, David M.
    University of Oklahoma, OK USA .
    Radfar, Lida
    University of Oklahoma, OK USA .
    Rohrer, Michael D.
    University of Minnesota, MN USA .
    Stone, Donald U.
    University of Oklahoma, OK USA .
    Wren, Jonathan D.
    Oklahoma Medical Research Fdn, OK USA .
    Vyse, Timothy J.
    Kings Coll London, England .
    Gaffney, Patrick M.
    Oklahoma Medical Research Fdn, OK USA .
    James, Judith A.
    Oklahoma Medical Research Fdn, OK USA .
    Omdal, Roald
    Stavanger University Hospital, Norway .
    Wahren-Herlenius, Marie
    Karolinska Institute, Sweden .
    Illei, Gabor G.
    National Institute Dent and Craniofacial Research, MD USA .
    Witte, Torsten
    Hannover Medical Sch, Germany .
    Jonsson, Roland
    Haukeland Hospital, Norway .
    Rischmueller, Maureen
    Queen Elizabeth Hospital, Australia .
    Ronnblom, Lars
    Uppsala University, Sweden .
    Nordmark, Gunnel
    Uppsala University, Sweden .
    Ng, Wan-Fai
    Newcastle University, England .
    Mariette, Xavier
    University of Paris 11, France .
    Anaya, Juan-Manuel
    University of Rosario, Colombia .
    Rhodus, Nelson L.
    University of Minnesota, MN USA .
    Segal, Barbara M.
    University of Minnesota, MN USA .
    Hal Scofield, R
    Oklahoma Medical Research Fdn, OK USA .
    Montgomery, Courtney G.
    Oklahoma Medical Research Fdn, OK USA .
    Harley, John B.
    Cincinnati Childrens Hospital Medical Centre, OH USA .
    Sivils, Kathy L.
    Oklahoma Medical Research Fdn, OK USA .
    Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjogren's syndrome2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1284-+Article in journal (Refereed)
    Abstract [en]

    Sjogrens syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogrens syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta andlt; 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogrens syndrome.

  • 36. Nordenskjöld, U
    et al.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Arbetsterapi vid reumatisk sjukdom 2011In: Reumatologi / [ed] Lars Klareskog, Tore Saxne, Yvonne Enman, 2011, 2, p. 423-Chapter in book (Other academic)
  • 37.
    Nordmark, G
    et al.
    Uppsala University.
    Kristjansdottir, G
    Uppsala University.
    Theander, E
    Malmö University Hospital.
    Appel, S
    University of Bergen, Norway.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Nephrology UHL.
    Vasaitis, L
    Uppsala University.
    Kvarnström, M
    Karolinska Institutet, Stockholm.
    Delaleu, N
    University of Bergen, Norway.
    Lundmark, P
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Lundmark, A
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Brun, J G
    Haukeland Hospital, Bergen, Norway.
    Jonsson, M V
    University of Bergen, Norway.
    Harboe, E
    Stavanger University Hospital, Norway.
    Gøransson, L G
    Stavanger University Hospital, Norway.
    Johnsen, S J
    Stavanger University Hospital, Norway.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Eloranta, M-L
    Uppsala University.
    Alm, G
    Swedish University of Agricultural Sciences, Uppsala.
    Baecklund, E
    Uppsala University.
    Wahren-Herlenius, M
    Karolinska Institutet, Stockholm.
    Omdal, R
    Stavanger University Hospital, Norway.
    Rönnblom, L
    Uppsala University.
    Jonsson, R
    University of Bergen, Norway.
    Syvänen, A-C
    Uppsala University.
    Association of EBF1, FAM167A(C8orf13)-BLK andTNFSF4 gene variants with primary Sjo¨gren’s syndrome2011In: Genes and Immunity, ISSN 1466-4879, E-ISSN 1476-5470, Vol. 12, no 2, p. 100-109Article in journal (Refereed)
    Abstract [en]

    We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10(-5), OR 1.68, the family with sequence similarity 167 member A-B-lymphoid tyrosine kinase (FAM167A-BLK) locus, P=4.7 × 10(-4), OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10(-4), OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS

  • 38.
    Nordmark, Gunnel
    et al.
    Uppsala University, Sweden .
    Wang, Chuan
    Uppsala University, Sweden .
    Vasaitis, Lilian
    Uppsala University, Sweden .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Theander, Elke
    Lund University, Sweden .
    Kvarnström, Marika
    Karolinska Institutet, Stockholm, Sweden.
    Forsblad-d'Elia, Helena
    University of Gothenburg, Sweden .
    Jazebi, Helmi
    Karolinska Institutet, Stockholm, Sweden.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Reksten, Tove Ragna
    University of Bergen, Norway .
    Brun, Johan G.
    Haukeland University Hospital, Bergen, Norway.
    Jonsson, Malin V.
    University of Bergen, Norway .
    Johnsen, Svein J.
    Stavanger University Hospital, Norway .
    Wahren-Herlenius, Marie
    Karolinska Institutet, Stockholm, Sweden.
    Omdal, Roald
    Stavanger University Hospital, Norway .
    Jonsson, Roland
    University of Bergen, Norway.
    Bowman, Simon
    University Hospital Birmingham, UK.
    Ng, Wan-Fai
    Newcastle University, UK.
    Eloranta, Maija-Leena
    Uppsala University, Sweden .
    Syvänen, Ann-Christine
    Uppsala University, Sweden .
    Association of Genes in the NF-κB Pathway with Antibody-Positive Primary Sjögren's Syndrome2013In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 78, no 5, p. 447-454Article in journal (Refereed)
    Abstract [en]

    Primary Sjogrens syndrome (SS) is a systemic autoimmune inflammatory disease characterized by focal lymphocytic infiltrates in the lachrymal and salivary glands and autoantibodies against the SSA/Ro and SSB/La antigens. Experimental studies have shown an activation of NF-B in primary SS. NF-B activation results in inflammation and autoimmunity and is regulated by inhibitory and activating proteins. Genetic studies have shown an association between multiple autoimmune diseases and TNFAIP3 (A20) and TNIP1 (ABIN1), both repressors of NF-B and of IKBKE (IKK epsilon), which is an NF-B activator. The aim of this study was to analyse single nucleotide polymorphisms (SNPs) in the IKBKE, NFKB1, TNIP1 and TNFAIP3 genes for association with primary SS. A total of 12 SNPs were genotyped in 1105 patients from Scandinavia (Sweden and Norway, n=684) and the UK (n=421) and 4460 controls (Scandinavia, n=1662, UK, n=2798). When patients were stratified for the presence of anti-SSA and/or anti-SSB antibodies (n=868), case-control meta-analysis found an association between antibody-positive primary SS and two SNPs in TNIP1 (P=3.4x10(-5), OR=1.33, 95%CI: 1.16-1.52 for rs3792783 and P=1.3x10(-3), OR=1.21, 95%CI: 1.08-1.36 for rs7708392). A TNIP1 risk haplotype was associated with antibody-positive primary SS (P=5.7x10(-3), OR=1.47, 95%CI: 1.12-1.92). There were no significant associations with IKBKE, NFKB1 or TNFAIP3 in the meta-analysis of the Scandinavian and UK cohorts. We conclude that polymorphisms in TNIP1 are associated with antibody-positive primary SS.

  • 39.
    Oman, Michael
    et al.
    Scania CV AB, Sweden .
    Nilsson, Larsgunnar
    Linköping University, Department of Management and Engineering, Solid Mechanics. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology in Östergötland.
    Structural optimization based on internal energy distribution2013In: Engineering optimization (Print), ISSN 0305-215X, E-ISSN 1029-0273, Vol. 45, no 4, p. 397-414Article in journal (Refereed)
    Abstract [en]

    Structural optimization is a valuable tool to improve the performance of products, but it is in general expensive to perform due to the required extensive number of function evaluations. Therefore, an approximate method based on the internal energy distribution, which only requires a small number of function evaluations, is presented here. By this method, structural optimization can be enabled already in the initial steps in the design of new products when fast, but not necessarily precise, results are often desired. However, the accuracy of the approximate solution depends on the structural behaviour. The internal energy based optimization method is here validated for three structures, but it is believed to be applicable to any structure subjected to a single load where the functions considered are related to the displacement of the loaded area and/or the material thicknesses of the structural parts.

  • 40.
    Pohl, Petra
    et al.
    Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology. Umeå University, Sweden .
    Dizdar (Dizdar Segrell), Nil
    Linköping University, Department of Clinical and Experimental Medicine, Neurology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Neurology.
    Hallert, Eva
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment and Health Economics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    The Ronnie Gardiner Rhythm and Music Method – a feasibility study in Parkinson’s disease2013In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 35, no 26, p. 2197-2204Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess the feasibility of the novel intervention, Ronnie Gardiner Rhythm and Music (RGRM™) Method compared to a control group for patients with Parkinson’s disease (PD).

    Method: Eighteen patients, mean age 68, participating in a disability study within a neurological rehabilitation centre, were randomly allocated to intervention group (n = 12) or control group (n = 6). Feasibility was assessed by comparing effects of the intervention on clinical outcome measures (primary outcome: mobility as assessed by two-dimensional motion analysis, secondary outcomes: mobility, cognition, quality of life, adherence, adverse events and eligibility).

    Results: Univariable analyses showed no significant differences between groups following intervention. However, analyses suggested that patients in the intervention group improved more on mobility (p = 0.006), cognition and quality of life than patients in the control group. There were no adverse events and a high level of adherence to therapy was observed.

    Conclusions: In this disability study, the use of the RGRM™ Method showed promising results in the intervention group and the adherence level was high. Our results suggest that most assessments chosen are eligible to use in a larger randomized controlled study for patients with PD.

    Implications for Rehabilitation

    • The RGRM™ Method appeared to be a useful and safe method that showed promising results in both motor and cognitive functions as well as quality of life in patients with moderate PD.

    • The RGRM™ Method can be used by physiotherapists, occupational, speech and music therapists in neurological rehabilitation.

    • Most measurements were feasible except for Timed-Up-and-Go.

     

     

  • 41.
    Reksten, Tove Ragna
    et al.
    University of Bergen, Norway / Uppsala University, Sweden .
    Johnsen, Svein Joar Auglænd
    Stavanger University Hospital, Norway.
    Jonsson, Malin Viktoria
    University of Bergen, Norway .
    Omdal, Roald
    Stavanger University Hospital, Norway.
    Brun, Johan G
    University of Bergen, Norway .
    Theander, Elke
    Skåne University Hospital, Lund University, Malmö, Sweden .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Wahren-Herlenius, Marie
    Karolinska Institutet, Stockholm, Sweden .
    Jonsson, Roland
    University of Bergen, Norway / Haukeland University Hospital, Bergen, Norway .
    Nordmark, Gunnel
    Uppsala University, Sweden.
    Genetic associations to germinal centre formation in primary Sjogren's syndrome2014In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, no 6, p. 1253-1258Article in journal (Refereed)
    Abstract [en]

    Background Primary Sjögren's syndrome (pSS) is an autoimmune rheumatic disease mainly characterised by focal mononuclear cell infiltration in the salivary and lacrimal glands, and by the symptoms xerostomia and keratoconjunctivitis sicca. Germinal centre-like structures (GC) are found in the minor salivary glands of approximately 25% of patients. In this study, we aimed to assess genetic variations in pSS patients with GC-like formations (GC+) compared with patients without such formations (GC−).                                

    Methods Minor salivary gland biopsies from Swedish and Norwegian pSS patients (n=320) were evaluated for GC-like formations, identifying 76 GC+ and 244 GC− patients. A panel of 1536 single-nucleotide polymorphisms (SNPs) in 107 genes was genotyped. Minor allele frequencies in GC+ and GC− patients were compared using Fisher's exact test, and associations were considered significant when p<4.7×10−4 and suggestive when p<0.01.                                

    Results In this case-only analysis, we identified two SNPs in CCL11 (eotaxin) associated with GC-like structures (p<4.7×10−4, OR 0.45 and 0.41, respectively). A haplotype of the two minor alleles was associated with GC status with p=2.6×10−4, OR 0.40. Suggestive associations (p<0.01) were found in SNPs in the B cell activation and/or GC-formation related genes AICDA, BANK1 and BCL2. Furthermore, SNPs in IL17A, ICA1, PKN1 and SNPs in the NF-κB pathway genes CARD8, IKBKE and TANK were found suggestively associated with GC-like structures.                                

    Conclusions Our findings suggest that genetic variations may explain why ectopic GC-like structures are present in some pSS patients, and support the hypothesis that GC+ and GC− patients represent distinct disease phenotypes.

  • 42.
    Rusakiewicz, Sylvie
    et al.
    Institut Gustave Roussy (IGR), Villejuif, France .
    Nocturne, Gaetane
    Université Paris-Sud, Le Kremlin Bicêtre, France.
    Lazure, Thierry
    Hôpitaux Universitaires Paris-Sud, Le Kremlin Bicêtre, France. .
    Semeraro, Michaela
    Institut Gustave Roussy (IGR), Villejuif, France .
    Flament, Caroline
    Institut Gustave Roussy (IGR), Villejuif, France .
    Caillat-Zucman, Sophie
    Hôpital St-Vincent de Paul, Paris, France.
    Sene, Damien
    Hôpital St-Vincent de Paul, Paris, France.
    Delahaye, Nicolas
    Institut Gustave Roussy (IGR), Villejuif, France .
    Vivier, Eric
    Centre d'Immunologie Marseille Luminy, INSERM, U1104, France.
    Chaba, Kariman
    Institut Gustave Roussy (IGR), Villejuif, France .
    Poirier-Colame, Vichnou
    Institut Gustave Roussy (IGR), Villejuif, France .
    Nordmark, Gunnel
    Uppsala University, Sweden .
    Eloranta, Maija-Leena
    Uppsala University, Sweden .
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Theander, Elke
    Skåne University Hospital, Lund University, Malmö, Sweden.
    Forsblad-dElia, Helena
    Sahlgrenska Academy at University of Gothenburg, Sweden.
    Omdal, Roald
    Stavanger University Hospital, Norway .
    Wahren-Herlenius, Marie
    Karolinska Institutet, Stockholm, Sweden.
    Jonsson, Roland
    University of Bergen, Norway .
    Rönnblom, Lars
    Uppsala University, Sweden .
    Nititham, Joanne
    University of California, San Francisco, USA .
    Taylor, Kimberly E.
    University of California, San Francisco, USA .
    Lessard, Christopher J.
    University of Oklahoma Health Sciences Center, Oklahoma City, USA .
    Moser Sivils, Kathy L.
    University of Oklahoma Health Sciences Center, Oklahoma City, USA .
    Gottenberg, Jacques-Eric
    Strasbourg University Hospital, France .
    Criswell, Lindsey A.
    University of California, San Francisco, USA .
    Miceli-Richard, Corinne
    Institut Gustave Roussy (IGR), Villejuif, France .
    Zitvogel, Laurence
    Institut Gustave Roussy (IGR), Villejuif, France .
    Mariette, Xavier
    Université Paris-Sud, Le Kremlin Bicêtre, France.
    NCR3/NKp30 Contributes to Pathogenesis in Primary Sjögren’s Syndrome2013In: Science Translational Medicine, ISSN 1946-6234, E-ISSN 1946-6242, Vol. 5, no 195Article in journal (Refereed)
    Abstract [en]

    Primary Sjögrens syndrome (pSS) is a chronic autoimmune disease characterized by a lymphocytic exocrinopathy. However, patients often have evidence of systemic autoimmunity, and they are at markedly increased risk for the development of non-Hodgkins lymphoma. Similar to other autoimmune disorders, a strong interferon (IFN) signature is present among subsets of pSS patients, although the precise etiology remains uncertain. NCR3/NKp30 is a natural killer (NK)-specific activating receptor regulating the cross talk between NK and dendritic cells and type II IFN secretion. We performed a case-control study of genetic polymorphisms of the NCR3/NKp30 gene and found that rs11575837 (Gandgt;A) residing in the promoter was associated with reduced gene transcription and function as well as protection to pSS. We also demonstrated that circulating levels of NCR3/NKp30 were significantly increased among pSS patients compared with controls and correlated with higher NCR3/NKp30 but not CD16-dependent IFN-gamma secretion by NK cells. Excess accumulation of NK cells in minor salivary glands correlated with the severity of the exocrinopathy. B7H6, the ligand of NKp30, was expressed by salivary epithelial cells. These findings suggest that NK cells may promote an NKp30-dependent inflammatory state in salivary glands and that blockade of the B7H6/NKp30 axis could be clinically relevant in pSS.

  • 43.
    Sahdo, Berolla
    et al.
    Örebro University, Sweden.
    Fransén, Karin
    Örebro University, Sweden.
    Asfaw Idosa, Berhane
    Örebro University, Sweden.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Söderquist, Bo
    Örebro University Hospital, Sweden.
    Kelly, Anne
    Örebro University Hospital and Örebro University, Sweden.
    Särndahl, Eva
    Örebro University, Sweden.
    Cytokine Profile in a Cohort of Healthy Blood Donors Carrying Polymorphisms in Genes Encoding the NLRP3 Inflammasome2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10Article in journal (Refereed)
    Abstract [en]

    Background: The NLRP3 inflammasome has been recognized as one of the key components of the innate immunity by sensing a diversity of insults. Inflammasome activation results in the maturation of the pro-inflammatory cytokines interleukin (IL)-1 beta and IL-18. Increased production of IL-1 beta is found in patients with gain-of-function polymorphisms in genes encoding the NLRP3 inflammasome. Since approximately 5% of the Swedish population are heterozygote carriers of these combined gene variants, their impact on inflammasome status and a relationship on disease development is therefore highly relevant to study. The present study investigates levels of inflammasome-produced cytokines as a measure of inflammasome activation in healthy individuals carrying Q705K polymorphism in the NLRP3 gene combined with C10X in the CARD8 gene. Materials and Methods: Genotyping of 1006 healthy blood donors was performed for the polymorphisms Q705K in the NLRP3 and C10X in the CARD8 genes. IL-1 beta, IL-18, IL-33, as well as a number of other pro-inflammatory cytokines, were analyzed by Luminex or ELISA in plasma from individuals carrying the polymorphisms and in age and gender matched non-carrier controls. Results & Discussion: The prevalence of the polymorphisms was in line with previous studies. Plasma levels of IL-1 beta and IL-33 were elevated among carriers of combined Q705K+C10X polymorphisms compared to controls, whereas no difference was found for IL-18 and the other cytokines measured. Moreover, carriers of C10X or Q705K per se had similar plasma levels of IL-1 beta as non-carriers. These data suggest that the combined polymorphisms create inflammasomes with increased basal activation state, which might provide a more favourable innate immune response. In spite of this, it could also represent the mechanisms by which the inflammatory loop is triggered into a long-term inflammatory phenotype.

  • 44.
    Salomonsson, S.
    et al.
    Karolinska Institutet, Stockholm.
    Dzikaite, V.
    Karolinska Institutet, Stockholm.
    Zeffer, E.
    Karolinska Institutet, Stockholm.
    Eliasson, H.
    Karolinska Institutet, Stockholm.
    Ambrosi, A.
    Karolinska Institutet, Stockholm.
    Bergman, G.
    Karolinska Institutet, Stockholm.
    Fernlund, E.
    Skåne University Hospital, Malmö.
    Theander, E.
    Skåne University Hospital, Malmö.
    Öhman, A.
    Uppsala University.
    Rydberg, A.
    Umeå University.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Wållberg-Jonsson, S.
    Umeå University.
    Elfving, Å.
    Karolinska Institutet, Stockholm.
    Fored, M.
    Karolinska Institutet, Stockholm.
    Ekbom, A.
    Karolinska Institutet, Stockholm.
    Lundström, U.
    The Queen Silvia Children′s Hospital, Sahlgrenska University Hospital, Göteborg.
    Mellander, M.
    The Queen Silvia Children′s Hospital, Sahlgrenska University Hospital, Göteborg, Sweden.
    Winqvist, O.
    Karolinska Institutet, Stockholm.
    Sonesson, S.-E.
    Karolinska Institutet, Stockholm.
    Gadler, F.
    Karolinska Institutet, Stockholm.
    Jonzon, A.
    Uppsala University.
    Wahren-Herlenius, M.
    Karolinska Institutet, Stockholm.
    A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block2011In: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 74, no 5, p. 511-517Article in journal (Refereed)
    Abstract [en]

    The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

  • 45.
    Sandin, Charlotta
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Region Östergötland, Heart and Medicine Center, Department of Nephrology. Linköping University, Faculty of Medicine and Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Faculty of Medicine and Health Sciences.
    IgA- and SIgA anti-PR3 antibodies in serum versus organ involvement and disease activity in PR3-ANCA associated vasculitis.2016In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 184, no 2, p. 208-215Article in journal (Refereed)
    Abstract [en]

    Circulating IgA class anti-neutrophil cytoplasm antibodies (ANCA) directed against proteinase 3 (PR3) have been reported in ANCA-associated vasculitis (AAV) with mucosal involvement. However, secretory IgA (SIgA) PR3-ANCA has not been reported previously. In this study we compared serum levels of SIgA PR3-ANCA and IgA PR3-ANCA with IgG PR3-ANCA in relation to disease characteristics. Among 73 patients with AAV and PR3-ANCA at diagnosis, 84% tested positive for IgG PR3-ANCA, 47% for IgA-ANCA and 36% for SIgA PR3-ANCA at the time of sampling for the present study. IgA and IgG PR3-ANCA were similarly represented among patients with different organ manifestations, i.e. upper airway, lung or kidney at time of sampling. However, SIgA PR3-ANCA was significantly less represented among patients with upper airway involvement. During active disease, the proportions of IgA PR3-ANCA and SIgA PR3-ANCA positive patients were significantly higher as compared to inactive disease. Eight patients were prospectively sampled during 24 months from onset of active disease. In these patients, IgA PR3-ANCA and SIgA PR3-ANCA more often turned negative after remission induction as compared to IgG PR3-ANCA. Our findings suggest that serum IgA PR3-ANCA and SIgA PR3-ANCA are more closely related to disease activity in AAV as compared to IgG PR3-ANCA. Further studies are required to reveal if this has implications for disease activity monitoring. The mean number of PR3-ANCA isotypes increased along with disease activity, suggesting a global B-cell activation during active disease. This article is protected by copyright. All rights reserved.

  • 46.
    Simard, Julia F
    et al.
    Karolinska Institutet, Stockholm; Stanford School of Medicine, CA, USA.
    Sjöwall, Christopher
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology. Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine.
    Rönnblom, Lars
    Uppsala University, Sweden.
    Jönsen, Andreas
    Lund University, Sweden.
    Svenungsson, Elisabet
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Systemic Lupus Prevalence in Sweden in 2010: What do national registers say?2014In: Arthritis care & research, ISSN 2151-4658, Vol. 66, no 11, p. 1710-1717Article in journal (Refereed)
    Abstract [en]

    Objective: Worldwide prevalence estimates of systemic lupus erythematosus (SLE) range from 3-207 per 100,000 depending on region and population, SLE definition, case sources and other methodological considerations. We aimed to determine the prevalence of SLE in Sweden on January 1, 2010 using population-based registers.

    Methods: Linking multiple national registers we identified all possible inpatient and outpatient visits with SLE-specific discharge diagnoses and relevant prescription dispensations among living individuals registered in Sweden on January 1, 2010. SLE was defined from a lenient classification (requiring only a single visit) to stricter definitions, which required multiple visits with a history of relevant specialist care and a dispensation for common SLE medications. Prevalence was calculated overall, and by sex, age (0-14, 15-49, 50+yrs, as well as in 5-year age groups), and county of residence.

    Result: Overall prevalence ranged from 46 per 100,000 for the strictest definition to 85 per 100,000 for the least strict definition. As expected, SLE was more common among females (ranged from 79 to 144/100,000) than males (12-25/100,000) and varied by age. The up to four-fold variation by county was unexpected. Prevalence generally increased with age (2, 52, and 95 per 100,000 by increasing age group, 0-14/15-49/50+, using a moderately strict definition) and also varied by county.

    Conclusion: Variations of prevalence by age and sex were consistent with previous studies and overall ranged from 46 to 85 per 100,000. We observed a surprising geographical variation in the prevalence of SLE in Sweden on January 1, 2010 according to multiple definitions.

  • 47.
    Sjöwall, Christoffer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Rheumatology in Östergötland.
    Cardell, Kristina
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Bokarewa, Maria I
    University of Gothenburg.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Ekstedt, Mattias
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    Lindvall, Liselott
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences.
    Frydén, Aril
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Infectious Diseases in Östergötland.
    Almer, Sven
    Linköping University, Department of Clinical and Experimental Medicine, Gastroenterology and Hepatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Endocrinology and Gastroenterology UHL.
    High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation2012In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, no 4, p. 382-388Article in journal (Refereed)
    Abstract [en]

    The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.

  • 48.
    Sjöwall, Christoffer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Almroth, Gunnel
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Beware of Antibodies to Dietary Proteins in "Antigen-specific" Immunoassays! Falsely Positive Anticytokine Antibody Tests Due to Reactivity with Bovine Serum Albumin in Rheumatoid Arthritis (The Swedish TIRA Project)2011In: JOURNAL OF RHEUMATOLOGY, ISSN 0315-162X, Vol. 38, no 2, p. 215-220Article in journal (Refereed)
    Abstract [en]

    Objective. To evaluate (1) to what extent sera from healthy subjects and patients with rheumatoid arthritis (RA) contain antibodies to bovine serum albumin (BSA); and (2) if anti-BSA antibodies interfere with results of enzyme-linked immunoassays (ELISA) containing BSA. Methods. The ELISA used was a previously developed in-house assay of autoantibodies to tumor necrosis factor (TNF). Anti-TNF and anti-BSA antibodies were analyzed by ELISA in 189 patients with early RA and 186 healthy blood donors. TNF preparations containing either BSA or human serum albumin (HSA) as carrier proteins were used as antigens in the anti-TNF assay. The presence and levels of antibodies were analyzed in relation to disease course and to the presence/absence of rheumatoid factor (RF). Results. In patients with RA, anti-TNF/BSA levels strongly correlated with anti-BSA levels (r = 0.81, p andlt; 0.001), whereas anti-TNF/HSA did not (r = -0.09). Neither the presence nor the levels of anti-BSA in RA patients were associated with disease progression, and antibody levels were not significantly altered compared to controls (p = 0.11). IgG reactivity with TNF/HSA was neglible. In paired sera, preincubation with BSA abolished the anti-TNF/BSA reactivity. There were no indications of RF interference with anti-BSA or anti-TNF reactivity. Conclusion. Antibodies to BSA are common in patients with RA as well as in healthy individuals. Their presence does not seem to be associated with RA disease activity or disease course, but may severely interfere with ELISA containing BSA. The use of BSA as a "blocking agent" or carrier protein in immunoassays should therefore be avoided.

  • 49.
    Sjöwall, Christoffer
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Olin, Anders I.
    Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Mörgelin, Matthias
    Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Nived, Ola
    Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Sturfelt, Gunnar
    Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Bengtsson, Anders A.
    Rheumatology, Department of Clinical Sciences, Lund University, Lund, Sweden.
    C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis2013In: Autoimmunity, ISSN 0891-6934, E-ISSN 1607-842X, Vol. 46, no 3, p. 205-214Article in journal (Refereed)
    Abstract [en]

    The pattern recognition molecules C-reactive protein (CRP) and C1q are of big interest in relation to the pathogenesis of systemic lupus erythematosus (SLE). Circulating autoantibodies against CRP and C1q are frequently found in SLE patients with active disease, particularly in lupus nephritis (LN), and rising levels reportedly relate to disease activity and outcome. If CRP-, or dsDNA- and/or C1q-containing immune complexes (ICs) are pathogenic in LN, glomerular IgG-deposits would be expected to co-localize with these antigens. In search for proof of this concept, renal biospsies from patients with active LN (n=5) were examined with high-resolution immunogold electron microscopy. Renal biopsies from patients with Henoch-Schönlein purpura, pauci-immune nephritis and renal cancer served as controls. IgG antibodies against CRP, C1q and nucleosomes were analyzed in pre–post flare sera. We could demonstrate that CRP, C1q, C3c and dsDNA were co-localized with IgG in electron dense deposits in the glomerular basement membrane/subendothelial space in all of the 5 LN patients. Deposits of IgG, CRP, complement and dsDNA were 10-fold higher in LN compared to controls. All SLE patients had circulating anti-nucleosome antibodies; 4/5 had serum antibodies against CRP, dsDNA, and C1q at biopsy/flare. Despite a limited number of cases, the results support the notion of a pathogenic role not only for anti-dsDNA antibodies, but also for anti-CRP and anti-C1q in LN. The glomerular ICs may have been generated by deposition of circulating ICs or by in situ IC formation.

  • 50.
    Sjöwall, Christopher
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Cöster, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Rheumatology.
    Belimumab may not prevent lupus nephritis in serologically active patientswith ongoing non-renal disease activity2014In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, no 5, p. 428-430Article in journal (Other academic)
12 1 - 50 of 67
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