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  • 1.
    Appelgren, Daniel
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Skogman, Barbro H
    Center for Clinical Research Dalarna-Uppsala University, Region Dalarna and Faculty of Medicine and Health Sciences, Örebro University.
    Nordberg, Marika
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Perander, Linda
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Nyman, Dag
    Bimelix AB, AX-22 100 Mariehamn, Åland, Finland.
    Nyberg, Clara
    Åland Central Hospital, Department of Infectious Diseases, AX-22 100 Mariehamn, Åland, Finland.
    Knopf, Jasmin
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Muñoz, Luis E
    Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), DE-91 054 Erlangen, Germany.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Johanna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Infectious Diseases.
    Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.2019In: Cells, ISSN 2073-4409, Vol. 9, no 1, article id E43Article in journal (Refereed)
    Abstract [en]

    Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (rs = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation.

  • 2.
    Bergström, Maria
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Sverker, Annette
    Linköping University, Department of Culture and Society, Division of Social Work. Linköping University, Faculty of Arts and Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Activity and Health.
    Larsson Ranada, Åsa
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Valtersson, Eva
    Linköping University, Department of Health, Medicine and Caring Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Activity and Health.
    Thyberg, Ingrid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Ostlund, Gunnel
    Malardalen Univ, Sweden.
    Björk, Mathilda
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Significant others influence on participation in everyday life - the perspectives of persons with early diagnosed rheumatoid arthritis2020In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165, Vol. 42, no 3, p. 385-393Article in journal (Refereed)
    Abstract [en]

    Purpose: To describe the meaning of significant others in relation to participation in everyday life of persons with early diagnosed rheumatoid arthritis (RA). Materials and methods: Fifty-nine persons participated in this interview study. Inclusion criteria were three years experience of diagnosis and being of working age. Semi-structured interviews were conducted using critical incident technique (CIT), and the material was analysed using content analysis. Results: Four categories were revealed: (1) My early RA causes activity adaptations for us all, referring to the person and significant others modifying activities. (2) Making the significant others balance between shortfalls and participation, where the participants distinguished between needing help and feeling involved in activities. (3) Physical interactions with significant others, referring to both the problematic and manageable impact RA could have on body contact. (4) Emotions in relation to activities with others, where participants described feelings of failing others, and anxiety about future activities. Conclusions: For persons with early diagnosed RA, significant others can be both hindering and facilitating for participation in everyday life. As a clinical implication, it is valuable to identify how significant others can be involved in the rehabilitation process, to enhance participation in everyday life early in the disease process.

  • 3.
    Enocsson, Helena
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Wirestam, Lina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Padyukov, Leonid
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Jonsen, Andreas
    Lund Univ, Sweden.
    Urowitz, Murray B.
    Toronto Western Hosp, Canada; Univ Toronto, Canada.
    Gladmane, Dafna D.
    Toronto Western Hosp, Canada; Univ Toronto, Canada.
    Romero-Diaz, Juanita
    Inst Nacl Ciencias Med and Nutr Salvador Zubiran, Mexico.
    Bae, Sang-Cheol
    Hanyang Univ, South Korea.
    Fortin, Paul R.
    Univ Laval, Canada.
    Sanchez-Guerrero, Jorge
    Toronto Western Hosp, Canada; Univ Toronto, Canada.
    Clarke, Ann E.
    Univ Calgary, Canada.
    Bernatsky, Sasha
    McGill Univ, Canada.
    Gordon, Caroline
    Univ Birmingham, England.
    Hanly, John G.
    Queen Elizabeth 2 Hlth Sci Ctr, Canada; Queen Elizabeth 2 Hlth Sci Ctr, Canada; Dalhousie Univ, Canada.
    Wallace, Daniel J.
    Univ Calif Los Angeles, CA USA.
    Isenberg, David A.
    UCL, England.
    Rahman, Anisur
    UCL, England.
    Merrill, Joan T.
    Oklahoma Med Res Fdn, OK 73104 USA.
    Ginzler, Ellen
    Suny Downstate Med Ctr, NY 11203 USA.
    Alarcon, Graciela S.
    Univ Alabama Birmingham, AL 35294 USA.
    Chatham, W. Winn
    Univ Alabama Birmingham, AL 35294 USA.
    Petri, Michelle
    Johns Hopkins Univ, MD USA.
    Khamashta, Munther
    Kings Coll London, England.
    Aranow, Cynthia
    Feinstein Inst Med Res, NY USA.
    Mackay, Meggan
    Feinstein Inst Med Res, NY USA.
    Dooley, Mary Anne
    Univ N Carolina, NC 27515 USA.
    Manzi, Susan
    Allegheny Hlth Network, PA USA.
    Ramsey-Goldman, Rosalind
    Northwestern Univ, IL 60611 USA; Feinberg Sch Med, IL USA.
    Nived, Ola
    Lund Univ, Sweden.
    Steinsson, Kristjan
    Landspitali Univ Hosp, Iceland.
    Zoma, Asad A.
    Hairmyres Hosp, Scotland.
    Ruiz-Irastorza, Guillermo
    Univ Basque Country, Spain.
    Lim, S. Sam
    Emory Univ, GA USA.
    Kalunian, Kenneth C.
    UCSD Sch Med, CA USA.
    Inanc, Murat
    Istanbul Univ, Turkey.
    van Vollenhoven, Ronald F.
    Univ Amsterdam, Netherlands; Free Univ VU Amsterdam, Netherlands; Amsterdam Rheumatol and Immunol Ctr, Netherlands.
    Ramos-Casals, Manuel
    Hosp Clin Barcelona, Spain.
    Kamen, Diane L.
    Med Univ South Carolina, SC 29425 USA.
    Jacobsen, Soren
    Copenhagen Univ Hosp, Denmark.
    Peschken, Christine A.
    Univ Manitoba, Canada.
    Askanase, Anca
    Columbia Univ, NY USA.
    Stoll, Thomas
    Kantousspital, Switzerland.
    Bruce, Ian N.
    Univ Manchester, England; Manchester Univ Hosp NHS Fdn Trust, England.
    Wetterö, Jonas
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Soluble urokinase plasminogen activator receptor (suPAR) levels predict damage accrual in patients with recent-onset systemic lupus erythematosus2020In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 106, article id 102340Article in journal (Refereed)
    Abstract [en]

    Objective

    The soluble urokinase plasminogen activator receptor (suPAR) has potential as a prognosis and severity biomarker in several inflammatory and infectious diseases. In a previous cross-sectional study, suPAR levels were shown to reflect damage accrual in cases of systemic lupus erythematosus (SLE). Herein, we evaluated suPAR as a predictor of future organ damage in recent-onset SLE.

    Methods

    Included were 344 patients from the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort who met the 1997 American College of Rheumatology classification criteria with 5-years of follow-up data available. Baseline sera from patients and age- and sex-matched controls were assayed for suPAR. Organ damage was assessed annually using the SLICC/ACR damage index (SDI).

    Results

    The levels of suPAR were higher in patients who accrued damage, particularly those with SDI≥2 at 5 years (N = 32, 46.8% increase, p = 0.004), as compared to patients without damage. Logistic regression analysis revealed a significant impact of suPAR on SDI outcome (SDI≥2; OR = 1.14; 95% CI 1.03–1.26), also after adjustment for confounding factors. In an optimized logistic regression to predict damage, suPAR persisted as a predictor, together with baseline disease activity (SLEDAI-2K), age, and non-Caucasian ethnicity (model AUC = 0.77). Dissecting SDI into organ systems revealed higher suPAR levels in patients who developed musculoskeletal damage (SDI≥1; p = 0.007).

    Conclusion

    Prognostic biomarkers identify patients who are at risk of acquiring early damage and therefore need careful observation and targeted treatment strategies. Overall, suPAR constitutes an interesting biomarker for patient stratification and for identifying SLE patients who are at risk of acquiring organ damage during the first 5 years of disease.

  • 4.
    Eriksson, Per
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, 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 Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Systemisk vaskulit2018In: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias, Leif Stenke, Stockholm: Liber, 2018, 6, Vol. Sidorna 939-949, p. 939-949Chapter in book (Other academic)
  • 5.
    Gutefeldt, Kerstin
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Hedman, Christina
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Thyberg, Ingrid
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Bachrack Lindström, Margareta
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Arnqvist, Hans
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Spångeus, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Low health-related quality of life is strongly linked to upper extremity impairments in type 1 diabetes with a long duration2020In: Disability and Rehabilitation, ISSN 0963-8288, E-ISSN 1464-5165Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare health-related quality of life (HRQOL) in type 1 diabetes and non-diabetic controls and possible links to upper extremity impairments (UEIs). Prevalence of sick-leave and causes were investigated.

    Materials and methods: This Swedish population-based case-control study included type 1 diabetes patients <67 years old and with a diabetes duration ≥20 years. Participants completed a postal questionnaire including Short Form 36, and questions regarding UEIs, and sick-leave.

    Results: In total, 773 patients, aged 50 ± 10 years (diabetes duration 35 ± 10 years), and 708 non-diabetic controls, aged 54 ± 9 years, completed the study. Patients reported significantly lower HRQOL compared with controls. The difference was greatest for general health, vitality, and bodily pain. Patients with shoulder or hand but not finger impairments scored significantly lower than asymptomatic patients. The prevalence of sick leave was higher in patients vs. controls (23% vs. 9%, p < 0.001), and nearly half cited impairments from back, muscles, or joints as the main reason.

    Conclusions: Health-related quality of life is lower in type 1 diabetes than controls and in patients with shoulder and hand impairments than in asymptomatic. Musculoskeletal impairments (back/muscle/joints) have impact on work ability. Identification of UEIs is important for initiating preventative-, therapeutic-, and rehabilitative interventions.

    • Implications for rehabilitation
    • Upper extremity impairments (UEIs) that are common in type 1 diabetes, and associated with reduced health-related quality of life, should preferably be screened for on a regular basis along with other known diabetes complications.

    • Early identification of UEIs is important to improve health by initiating preventive as well as therapeutic multi-professional rehabilitative interventions.

    • Sick leave is higher in type 1 diabetes than in controls. Musculoskeletal impairments, including the back, muscles, and joints, are a common cause for sick leave warranting further studies.

  • 6.
    Huoman, Johanna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Papapavlou, Georgia
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Pap, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Alm, Johan
    Karolinska Institutet, Department of Clinical Science and Education, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
    Nilsson, Lennart J
    Region Östergötland, Heart and Medicine Center, Allergy Center. Linköping University, Department of Biomedical and Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Jenmalm, Maria C
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sublingual immunotherapy alters salivary IgA and systemic immune mediators in timothy allergic children.2019In: Pediatric Allergy and Immunology, ISSN 0905-6157, E-ISSN 1399-3038, Vol. 30, no 5, p. 522-530Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Immunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy-related cytokine and chemokine levels, as well as IgA-responses upon a 3-year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis.

    METHODS: From children included in the GRAZAX® Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3 years of treatment, and 2 years after treatment ending. By means of Luminex and ELISA methodologies, allergy-related cytokines and chemokines were measured in plasma samples and allergen-stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1-specific salivary IgA antibodies were performed using the same methods.

    RESULTS: GRAZAX® -treated children exhibited significantly higher levels of Phl p 1-specific salivary IgA and serum IgG4 , along with significantly lower skin prick test positivity, after 3 years of treatment and 2 years after treatment cessation. Additionally, plasma levels of the Th1-associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points. Timothy-induced ratios of IL-5/IL-13 over IFN-γ were significantly decreased after 3 years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters.

    CONCLUSION: Phleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically-by increasing Th1-responses, decreasing Th2-responses, and inducing immunoregulatory responses-all signs of tolerance induction.

  • 7.
    Håkansson, Irene
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Ernerudh, Jan
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Vrethem, Magnus
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Neurology in Linköping.
    Dahle, Charlotte
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Ekdahl, Kristina N.
    Centre of Biomaterials Chemistry, Linnaeus University, Kalmar, Sweden ; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
    Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis2020In: Journal of Neuroimmunology, ISSN 0165-5728, E-ISSN 1872-8421, Vol. 340, article id 577147Article in journal (Refereed)
    Abstract [en]

    To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≀ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.

  • 8.
    Nasr, Patrik
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Gastroentorology.
    Fredrikson, Mats
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences, Forum Östergötland.
    Ekstedt, Mattias
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Kechagias, Stergios
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.2020In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.

    METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC.

    RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).

    CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

  • 9.
    Ramírez Sepúlveda, Jorge I
    et al.
    Rheumatology Unit, Department of Medicine, Karolinska Institutet.
    Bolin, Karin
    Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Mofors, Johannes
    Rheumatology Unit, Department of Medicine, Karolinska Institutet.
    Leonard, Dag
    Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Svenungsson, Elisabet
    Rheumatology Unit, Department of Medicine, Karolinska Institutet // Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
    Jönsen, Andreas
    Department of Clinical Sciences, Rheumatology, Lund University, Skåne University Hospital, Lund, Sweden.
    Bengtsson, Christine
    Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.
    Nordmark, Gunnel
    Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Rantapää Dahlqvist, Solbritt
    Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.
    Bengtsson, Anders A
    Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden.
    Rönnblom, Lars
    Department of Medical Sciences, Rheumatology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Gunnarsson, Iva
    Rheumatology Unit, Department of Medicine, Karolinska Institutet // Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
    Wahren-Herlenius, Marie
    Rheumatology Unit, Department of Medicine, Karolinska Institutet // Rheumatology, Karolinska University Hospital, Stockholm, Sweden.
    Sex differences in clinical presentation of systemic lupus erythematosus.2019In: Biology of sex differences, ISSN 2042-6410, Vol. 10, no 1, article id 60Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Systemic lupus erythematosus (SLE) predominantly affects women, but previous studies suggest that men with SLE present a more severe disease phenotype. In this study, we investigated a large and well-characterized patient group with the aim of identifying sex differences in disease manifestations, with a special focus on renal involvement.

    METHODS: We studied a Swedish multi-center SLE cohort including 1226 patients (1060 women and 166 men) with a mean follow-up time of 15.8 ± 13.4 years. Demographic data, disease manifestations including ACR criteria, serology and renal histopathology were investigated. Renal outcome and mortality were analyzed in subcohorts.

    RESULTS: Female SLE patients presented more often with malar rash (p < 0.0001), photosensitivity (p < 0.0001), oral ulcers (p = 0.01), and arthritis (p = 0.007). Male patients on the other hand presented more often with serositis (p = 0.0003), renal disorder (p < 0.0001), and immunologic disorder (p = 0.04) by the ACR definitions. With regard to renal involvement, women were diagnosed with nephritis at an earlier age (p = 0.006), while men with SLE had an overall higher risk for progression into end-stage renal disease (ESRD) with a hazard ratio (HR) of 5.1 (95% CI, 2.1-12.5). The mortality rate among men with SLE and nephritis compared with women was HR 1.7 (95% CI, 0.8-3.8).

    CONCLUSION: SLE shows significant sex-specific features, whereby men are affected by a more severe disease with regard to both renal and extra-renal manifestations. Additionally, men are at a higher risk of developing ESRD which may require an increased awareness and monitoring in clinical practice.

  • 10.
    Rao Muvva, Jagadeeswara
    et al.
    Karolinska Inst, Sweden.
    Venkata Ramanarao, Parasa
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Lerm, Maria
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Svensson, Mattias
    Karolinska Inst, Sweden.
    Brighenti, Susanna
    Karolinska Inst, Sweden.
    Polarization of Human Monocyte-Derived Cells With Vitamin D Promotes Control of Mycobacterium tuberculosis Infection2020In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 10, article id 3157Article in journal (Refereed)
    Abstract [en]

    Background: Understanding macrophage behavior is key to decipher Mycobacterium tuberculosis (Mtb) pathogenesis. We studied the phenotype and ability of human monocyte-derived cells polarized with active vitamin D [1,25(OH)(2)D-3] to control intracellular Mtb infection compared with polarization of conventional subsets, classical M1 or alternative M2. Methods: Human blood-derived monocytes were treated with active vitamin D or different cytokines to obtain 1,25(OH)(2)D-3-polarized as well as M1- and M2-like cells or fully polarized M1 and M2 subsets. We used an in vitro macrophage Mtb infection model to assess both phenotype and functional markers i.e., inhibitory and scavenger receptors, costimulatory molecules, cytokines, chemokines, and effector molecules using flow cytometry and quantitative mRNA analysis. Intracellular uptake of bacilli and Mtb growth was monitored using flow cytometry and colony forming units. Results: Uninfected M1 subsets typically expressed higher levels of CCR7, TLR2, and CD86, while M2 subsets expressed higher CD163, CD200R, and CD206. Most of the investigated markers were up-regulated in all subsets after Mtb infection, generating a mixed M1/M2 phenotype, while the expression of CD206, HLADR, and CD80 was specifically up-regulated (P amp;lt; 0.05) on 1,25(OH)(2)D-3-polarized macrophages. Consistent with the pro-inflammatory features of M1 cells, Mtb uptake and intracellular Mtb growth was significantly (P amp;lt; 0.01-0.001 and P amp;lt; 0.05-0.01) lower in the M1 (19.3%) compared with the M2 (82.7%) subsets 4 h post-infection. However, infectivity rapidly and gradually increased in M1 cells at 24-72 h. 1,25(OH)(2)D-3-polarized monocyte-derived cells was the most potent subset to inhibit Mtb growth at both 4 and 72 h (P amp;lt; 0.05-0.01) post-Mtb infection. This ability was associated with high mRNA levels of pro-inflammatory cytokines and the antimicrobial peptide LL-37 but also anti-inflammatory IL-10, while expression of the immunosuppressive enzyme IDO (indoleamine 2,3-dioxygenase) remained low in Mtb-infected 1,25(OH)(2)D-3-polarized cells compared with the other subsets. Conclusions: Mtb infection promoted a mixed M1/M2 macrophage activation, and 1,25(OH)(2)D-3-polarized monocyte-derived cells expressing LL-37 but not IDO, were most effective to control intracellular Mtb growth. Macrophage polarization in the presence of vitamin D may provide the capacity to mount an antimicrobial response against Mtb and simultaneously prevent expression of inhibitory molecules that could accelerate local immunosuppression in the microenvironment of infected tissue.

  • 11.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Reumatiska systemsjukdomar2018In: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias, Leif Stenke, Stockholm: Liber, 2018, 6, Vol. Sidorna 920-939, p. 920-939Chapter in book (Other academic)
  • 12.
    Svärd, Anna
    et al.
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Roos, Karin
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Brink, M.
    Umea Univ, Sweden.
    Martinsson, Klara
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Dahlqvist, S. Rantapaa
    Umea Univ, Sweden.
    Kastbom, Alf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Secretory antibodies to citrullinated peptides in plasma and saliva from rheumatoid arthritis patients and their unaffected first-degree relatives2020In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 199, no 2, p. 143-149Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (amp;lt; 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.

  • 13.
    Wang, Yan
    et al.
    Karolinska Inst, Sweden.
    Lloyd, Katy A.
    Karolinska Inst, Sweden.
    Melas, Ioannis
    UCB Pharma, England.
    Zhou, Diana
    Karolinska Inst, Sweden.
    Thyagarajan, Radha
    Karolinska Inst, Sweden.
    Lindqvist, Joakim
    Karolinska Inst, Sweden.
    Hansson, Monika
    Karolinska Inst, Sweden.
    Svärd, Anna
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Mathsson-Alm, Linda
    Thermo Fisher Sci, Sweden; Uppsala Univ, Sweden.
    Kastbom, Alf
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Lundberg, Karin
    Karolinska Inst, Sweden.
    Klareskog, Lars
    Karolinska Inst, Sweden.
    Catrina, Anca I.
    Karolinska Inst, Sweden.
    Rapecki, Stephen
    UCB Pharma, England.
    Malmstrom, Vivianne
    Karolinska Inst, Sweden.
    Gronwall, Caroline
    Karolinska Inst, Sweden.
    Rheumatoid arthritis patients display B-cell dysregulation already in the naive repertoire consistent with defects in B-cell tolerance2019In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 9, article id 19995Article in journal (Refereed)
    Abstract [en]

    B cells are postulated to be central in seropositive rheumatoid arthritis (RA). Here, we use exploratory mass cytometry (n = 23) and next-generation sequencing (n = 19) to study B-cell repertoire shifts in RA patients. Expression of several B-cell markers were significantly different in ACPA(+) RA compared to healthy controls, including an increase in HLA-DR across subsets, CD22 in clusters of IgM(+) B cells and CD11c in IgA(+) memory. Moreover, both IgA(+) and IgG(+) double negative (IgD(-) CD27(-)) CD11c(+) B cells were increased in ACPA+ RA, and there was a trend for elevation in a CXCR5/CCR6(high) transitional B-cell cluster. In the RA BCR repertoire, there were significant differences in subclass distribution and, notably, the frequency of VH with low somatic hypermutation (SHM) was strikingly higher, especially in IgG1 (p amp;lt; 0.0001). Furthermore, both ACPA(+) and ACPA(-) RA patients had significantly higher total serum IgA and IgM compared to controls, based on serology of larger cohorts (n = 3494 IgA; n = 397 IgM). The observed elevated Ig-levels, distortion in IgM(+) B cells, increase in double negative B cells, change in B-cell markers, and elevation of unmutated IgG(+) B cells suggests defects in B-cell tolerance in RA. This may represent an underlying cause of increased polyreactivity and autoimmunity in RA.

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