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  • 1.
    Ahlmén, M
    et al.
    SU.
    Nordenskiöld, U
    SU.
    Archenholtz, B
    SU.
    Thyberg, Ingrid
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Rönnqvist, R
    KI.
    Lindén, L
    KI.
    Andersson, A-K
    Mannerkorpi, K
    Rheumatology outcomes: The patient's perspective. A multicentre focus group interview study of Swedish rheumatoid arthritis patients2005In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 44, no 1, p. 105-110Article in journal (Refereed)
    Abstract [en]

    Objectives. Patients with rheumatoid arthritis (RA) and clinicians have different views about benefits from treatments. More knowledge is needed about how patients assess outcomes in order to update current measurements. Methods. Focus group interviews were performed at four Swedish rheumatology clinics. A total of 25 patients with RA were included, representing a wide range of ages and disease duration. Predetermined topics relating to important outcomes from and satisfaction/dissatisfaction with RA treatments were discussed. Results. The participants' initial outcome assessments included physical and psychosocial items, which comprised overall treatment goals such as impairment in social roles, fatigue, daily activities and self-confidence. The identified themes were 'Normal life', 'Physical capacity', 'Independence' and 'Well-being'. Satisfaction with treatment was associated with the quality of communication between staff and the patient. The participants assumed this as a prerequisite for a treatment to work. Patients wanted to be accepted as experts on their own bodies, and expected all clinicians to be experts on RA. This made it possible for patients to 'take charge' of their life situation. Good resources for and access to rheumatology care were desired. Conclusions. Suggesting a holistic approach to rheumatology care, the study results indicate that the illness and outcomes have to be evaluated within an individual RA patient's total life situation, described in the identified themes: 'Normal life', 'Physical capacity', 'Independence' and 'Well-being'. Development and validation of measurements covering these issues is suggested. More research is needed about communication and how patients experience their roles in the rheumatology clinic.

  • 2.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Eriksson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Berlin, G
    Andersson, B
    Hahn-Zoric, M
    Långtidsresultat av cyklofosfamidbehandling vid ANCA-associerad systemisk vaskulit med njurengagemang2004In: Svenska Läkaresällskapets,2004, 2004Conference paper (Other academic)
  • 3.
    Almroth, Gabriel
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Nephrology. Östergötlands Läns Landsting, Centre for Medicine, Department of Nephrology UHL.
    Eriksson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Berlin, G
    Hahn-Zoric, M
    Andersson, B
    Cyklophosphamide pulse treatment and infections in systemic vasculitis with renal involvement2004In: JASN 15 2004,2004, 2004Conference paper (Other academic)
  • 4.
    Ambrosi, Aurelie
    et al.
    Karolinska Institute.
    Salomonsson, Stina
    Karolinska Institute.
    Eliasson, Hakan
    Karolinska Institute.
    Zeffer, Elisabeth
    Karolinska Institute.
    Dzikaite, Vijole
    Karolinska Institute.
    Bergman, Gunnar
    Karolinska Institute.
    Fernlund, Eva
    Skane University Hospital.
    Theander, Elke
    Malmo University Hospital.
    Ryberg, Annika
    Umea University Hospital.
    Ohman, Annika
    Uppsala University.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Rantapaa, Solbritt
    Umea University Hospital.
    Fored, Michael
    Karolinska Institute.
    Blomqvist, Paul
    Karolinska Institute.
    Ekbom, Anders
    Karolinska Institute.
    Lindsrtom, Ulla
    Queen Silvia Childrens Hospital.
    Melander, Mats
    Queen Silvia Childrens Hospital.
    Winqvist, Ola
    Karolinska Institute.
    Gadler, Fredrik
    Karolinska Institute.
    Jonzon, Anders
    Uppsala University.
    Sonesson, Sven-Erik
    Karolinska Institute.
    Wahren-Herlenius, Marie
    Karolinska Institute.
    Influence of Season of Birth and Maternal Age in the Development of Congenital Heart Block in Anti-Ro-SSA/La-SSB Positive Pregnancies in SCANDINAVIAN JOURNAL OF IMMUNOLOGY, vol 72, issue 3, pp 265-2652010In: SCANDINAVIAN JOURNAL OF IMMUNOLOGY, Blackwell Publishing Ltd , 2010, Vol. 72, no 3, p. 265-265Conference paper (Refereed)
    Abstract [en]

    n/a

  • 5. Anfelter, P
    et al.
    Granerus, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Stenström, Hugo
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Medical Radiology. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology UHL.
    Eriksson, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Nyström, Fredrik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Internal Medicine. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
    The effect of percutaneous dilatation of renal arterial stenosis on captopril renography in hypertension2005In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 14, no 6, p. 359-365Article in journal (Refereed)
    Abstract [en]

    Background. The clinical effects of percutaneous transluminal renal artery angioplasty (PTRA) in patients with renal vascular stenosis and hypertension is controversial. Methods. We consecutively recruited all 23 patients referred for evaluation of renovascular hypertension that eventually underwent unilateral PTRA, to be investigated with captopril MAG3 renography (CR), both before and after the endovascular procedure. Data were evaluated on an intention-to-treat basis. Results. We found that the relative MAG3 clearance of the stenotic kidney increased (from 29.9 ± 14% to 35.1 ± 14%, p=0.01) and that the creatinine levels fell following the intervention (from 110 ± 19 to 99 ± 17 μmol/l, p=0.0003). Blood pressure levels were also lowered (from 173 ± 32/93 ± 17 to 158 ± 31/86 ± 15 mmHg, p<0.006) while the mean number of anti-hypertensive drugs was unchanged following PTRA (2.9 ± 1.4 before and 2.8 ± 1.3 drugs after the intervention, respectively, p-0.6). Conclusion. This prospective trial showed statistically significant improvements of individual kidney function as measured by CR and blood pressure in subjects with suspected renovascular hypertension treated with PTRA. Although the endovascular procedure was found to be safe, the magniture of the absolute improvements was rather modest. © 2005 Taylor & Francis.

  • 6.
    Askling, J
    et al.
    Karolinska University Hospital, Stockholm, Sweden.
    Baecklund, E
    Uppsala University Hospital, Uppsala, Sweden.
    Granath, F
    Karolinska University Hospital, Stockholm, Sweden.
    Geborek, P
    Lund University Hospital, Lund, Sweden.
    Fored, M
    Karolinska University Hospital, Stockholm, Sweden.
    Backlin, C
    Uppsala University, Uppsala, Sweden.
    Bertilsson, L
    Sahlgrens University Hospital, Gothenburg, Sweden.
    Cöster, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Jacobsson, L T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, S
    Karolinska University Hospital, Stockholm, Sweden.
    Lysholm, J
    Falu County Hospital, Falun, Sweden.
    Rantapaa-Dahlqvist, S
    Umeå University Hospital, Umeå, Sweden.
    Saxne, T
    University of Lund Hospital, Lund, Sweden.
    van Vollenhoven, R
    Karolinska University Hospital, Stockholm, Sweden.
    Klareskog, L
    Karolinska University Hospital, Stockholm, Sweden.
    Feltelius, N
    Medical Products Agency, Uppsala, Sweden.
    Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register2009In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 68, no 5, p. 648-653Article in journal (Refereed)
    Abstract [en]

    Background: Tumour necrosis factor (TNF) antagonists have proved effective as treatment against rheumatoid arthritis ( RA), but the unresolved issue of whether the use of anti-TNF therapy increases the already elevated risk of lymphoma in RA remains a concern.

    Methods: Using the Swedish Biologics Register (ARTIS), the Swedish Cancer Register, pre-existing RA cohorts and cross-linkage with other national health and census registers, a national RA cohort (n = 67 743) was assembled and patients who started anti-TNF therapy between 1998 and July 2006 ( n = 6604) were identified. A general population comparator ( n = 471 024) was also assembled and the incidence of lymphomas from 1999 to 31 December 2006 was assessed and compared in these individuals.

    Results: Among the 6604 anti-TNF-treated RA patients, 26 malignant lymphomas were observed during 26 981 person-years of follow-up, which corresponded to a relative risk (RR) of 1.35 (95% CI 0.82 to 2.11) versus anti-TNF-naive RA patients ( 336 lymphomas during 365 026 person-years) and 2.72 ( 95% CI 1.82 to 4.08) versus the general population comparator ( 1568 lymphomas during 3 355 849 person-years). RA patients starting anti-TNF therapy in 1998-2001 accounted for the entire increase in lymphoma risk versus the two comparators. By contrast, RR did not vary significantly by time since start of first treatment or with the accumulated duration of treatment, nor with the type of anti-TNF agent.

    Conclusion: Overall and as used in routine care against RA, TNF antagonists are not associated with any major further increase in the already elevated lymphoma occurrence in RA. Changes in the selection of patients for treatment may influence the observed risk.

  • 7. Askling, J
    et al.
    Fored, CM
    Baecklund, E
    Brandt, L
    Backlin, C
    Ekbom, A
    Sundström, C
    Bertilsson, L
    Cöster, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Geborek, P
    Jacobsson, Lt
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    Klareskog, L
    Feltelius, N
    Haematopoietic malignancies in rheumatoid arthritis: Lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists2005In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, no 10, p. 1414-1420Article in journal (Refereed)
    Abstract [en]

    Background: Patients with rheumatoid arthritis (RA) are at increased risk of malignant lymphomas, and maybe also of leukaemia and multiple myeloma. The effect of tumour necrosis factor (TNF) antagonists on lymphoma risk and characteristics is unclear. Objective: To assess expected rates and relative risks of haematopoietic malignancies, especially those associated with TNF antagonists, in large population based cohorts of patients with RA. Methods: A population based cohort study was performed of patients with RA (one prevalent cohort (n = 53 067), one incident cohort (n = 3703), and one TNF antagonist treated cohort 1999 through 2003 (n = 4160)), who were linked with the Swedish Cancer Register. Additionally, the lymphoma specimens for the 12 lymphomas occurring in patients with RA exposed to TNF antagonists in Sweden 1999 through 2004 were reviewed. Results: Study of almost 500 observed haematopoietic malignancies showed that prevalent and incident patients with RA were at increased risk of lymphoma (SIR =1.9 and 2.0, respectively) and leukaemia (SIR = 2.1 and 2.2, respectively) but not of myeloma. Patients with RA treated with TNF antagonists had a tripled lymphoma risk (SIR = 2.9) compared with the general population. After adjustment for sex, age, and disease duration, the lymphoma risk after exposure to TNF antagonists was no higher than in the other RA cohorts. Lymphomas associated with TNF antagonists had characteristics similar to those of other RA lymphomas. Conclusion: Overall, patients with RA are at equally increased risks for lymphomas and leukaemias. Patients with RA treated with TNF antagonists did not have higher lymphoma risks than other patients with RA. Prolonged observation is needed to determine the long term effects of TNF antagonists on lymphoma risk.

  • 8. Askling, J
    et al.
    Fored, CM
    Brandt, L
    Baecklund, E
    Bertilsson, L
    Feltelius, N
    Cöster, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Geborek, P
    Jacobsson, LT
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    Klareskog, L
    Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists2005In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, no 10, p. 1421-1426Article in journal (Refereed)
    Abstract [en]

    Background: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s. Objective: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials. Methods: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990-2003 (n = 53 067), one incident, diagnosed 1995-2003 (n = 3703), and one treated with TNF antagonists 1999-2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003. Results: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20-50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (-20%) and colorectal cancer (-25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA. Conclusion: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

  • 9. Askling, J
    et al.
    Fored, CM
    Brandt, L
    Baecklund, E
    Bertilsson, L
    Feltelius, N
    Cöster, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Geborek, P
    Jacobsson, LT
    Lindblad, S
    Lysholm, J
    Rantapää-Dahlqvist, S
    Saxne, T
    van Vollenhoven, RF
    Klareskog, L
    Time-dependent increase in risk of hospitalisation with infection among Swedish RA patients treated with TNF antagonists2007In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 66, no 10, p. 1339-1344Article in journal (Refereed)
    Abstract [en]

    Objectives: The degree to which treatment with tumour necrosis factor (TNF) antagonists may be associated with increased risks for serious infections is unclear. An observational cohort study was performed using prospectively collected data from the Swedish Biologics Register (ARTIS) and other national Swedish registers. Methods: First, in the ARTIS, all 4167 rheumatoid arthritis (RA) patients starting TNF antagonist treatment between 1999 and 2003 were identified. Secondly, in the Swedish Inpatient Register, all individuals hospitalised for any reason and who also carried a diagnosis of RA, between 1964 and 2003 (n = 44 946 of whom 2692 also occurred in ARTIS), were identified. Thirdly, in the Swedish Inpatient Register, all hospitalisations listing an infection between 1999 and 2003 were identified. By cross-referencing these three data sets, RRs for hospitalisation with infection associated with TNF antagonist treatment were calculated within the cohort of 44 946 RA patients, using Cox regression taking sex, age, geography, co-morbidity and use of inpatient care into account. Results: Among the 4167 patients treated with TNF antagonists, 367 hospitalisations with infections occurred during 7776 person-years. Within the cohort of 44 496 RA patients, the RR for infection associated with TNF antagonists was 1.43 (95% Cl 1.18 to 1.73) during the first year of treatment, 1.15 (95% Cl 0.88 to 1.51) during the second year of treatment, and 0.82 (95% Cl 0.62 to 1.08) for subjects remaining on their first TNF antagonist treatment after 2 years. Conclusion: Treatment with TNF antagonists may be associated with a small to moderate increase in risk of hospitalisation with infection, which disappears with increasing treatment duration.

  • 10. Askling, Johan
    et al.
    Fored, Michael
    Brandt, Lena
    Baecklund, Eva
    Bertilsson, Lennart
    Cöster, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Geborek, Pierre
    Jacobsson, Lennart T
    Lindblad, Staffan
    Lysholm, Jörgen
    Rantapää-Dahlqvist, Solbritt
    Saxne, Tore
    Romanus, Victoria
    Klareskog, Lars
    Feltelius, Nils
    Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden2005In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 52, no 7, p. 1986-1992Article in journal (Refereed)
    Abstract [en]

    Objective. Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low-risk populations, this study sought to determine the risk of TB among Swedish patients with RA. Methods. Using data from Swedish nationwide and population-based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004. Results. During 1999-2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2-3.4). RA patients treated with TNF antagonists had a 4-fold increased risk of TB (relative risk 4.0, 95% CI 1.3-12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999-2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment. Conclusion. Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999-2001, TNF antagonists were associated with an increased risk of TB, up to 4-fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept. © 2005, American College of Rheumatology.

  • 11.
    Askling, Johan
    et al.
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    van Vollenhoven, Ronald F
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Granath, Fredrik
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Raaschou, Pauline
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Fored, C Michael
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Baecklund, Eva
    Uppsala University Hospital, Uppsala, Sweden.
    Dackhammar, Christina
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Feltelius, Nils
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden, and Medical Products Agency, Uppsala, Sweden.
    Cöster, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Geborek, Pierre
    Lund University Hospital, Lund, Sweden.
    Jacobsson, Lennart T
    Malmö University Hospital, Malmö, Sweden.
    Lindblad, Staffan
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Rantapaa-Dahlqvist, Solbritt
    Norrland University Hospital, Umeå, Sweden.
    Saxne, Tore
    Lund University Hospital, Lund, Sweden.
    Klareskog, Lars
    Karolinska University Hospital at Solna and Karolinska Institutet, Stockholm, Sweden.
    Cancer Risk in Patients With Rheumatoid Arthritis Treated With Anti-Tumor Necrosis Factor alpha Therapies Does the Risk Change With the Time Since Start of Treatment?2009In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 11, p. 3180-3189Article in journal (Refereed)
    Abstract [en]

    Objective. To determine the short-term and medium-term risks of cancer in patients receiving antitumor necrosis factor alpha (anti-TNF alpha) therapies that have proven effective in the treatment of chronic inflammatory conditions. Methods. By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. Results. During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. Conclusion. During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.

  • 12.
    Aspegren Kendall, Sally
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Ekselius, L
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Sörén, B
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Feldenkrais intervention in fibromyalgia patients: A pilot study2001In: Journal of Musculoskeletal Pain, ISSN 1058-2452, E-ISSN 1540-7012, Vol. 9, no 4, p. 25-35Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the effect of the Feldenkrais intervention, in fibromyalgia patients. Methods: Twenty fibromyalgia patients started Feldenkrais intervention done as one individual and two group sessions weekly for 15 weeks. Nineteen started a group-based pain education program followed by a pool program. Test and self-report questionnaires were administered at the start, at six month follow up, and at the end of intervention. Results: After the Feldenkrais intervention improvement in balance and trends to better lower extremity muscle function were shown, but the improvements were not maintained. Conclusions: No sustained benefit of the Feldenkrais intervention compared to a pool program was seen. Methodological problems are discussed. ⌐ 2001 by The Haworth Press, Inc. All rights reserved.

  • 13.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    The muscle in fibromyalgia2002In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 41, no 7, p. 721-724Other (Other academic)
  • 14.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    The muscle in fibromyalgia.2002In: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 41, p. 721-724Article in journal (Refereed)
  • 15.
    Bengtsson, Ann
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Henriksson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Occupational Therapy.
    Henriksson, Karl-Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Fibromyalgi2006In: Rehabiliteringsmedicin / [ed] Jörgen Borg, Lund: Studentlitteratur , 2006, 1, p. 156-161Chapter in book (Other academic)
    Abstract [sv]

    Kapitel om rehabiliteringsmedicinens utveckling och nuvarande plats i sjukvården samt begrepp och metodik inleder boken. I två delar ges därefter rehabiliteringsmedicinska aspekter på de dominerande sjukdomsgrupperna - komplexa smärttillstånd respektive skador och sjukdomar i nervsystemet. Som avslutning beskrivs bland annat  stressrelaterade tillstånd. Läroboken är avsedd för grundutbildning av läkare, arbetsterapeuter och sjukgymnaster, logopeder samt för läkare under AT-tjänstgöring. Den är också lämplig som introduktion i specialistutbildningen i rehabiliteringsmedicin, geriatrik, neurologi och smärtlindring. Vidareutbildningar av olika vårdyrkesgrupper kan ha nytta av boken och den kan också användas som referenslitteratur av yrkesverksamma med intresse för rehabiliteringsmedicin.

  • 16.
    Cedergren, Jan
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences.
    Follin, Per
    Linköping University, Department of Clinical and Experimental Medicine, Infectious Diseases . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Forslund, Tony
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . Linköping University, Faculty of Health Sciences.
    Lindmark, Maria
    Linköping University, Department of Medicine and Care. Linköping University, Faculty of Health Sciences.
    Sundqvist, Tommy
    Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology . 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Inducible nitric oxide synthase (NOS II) is constitutive in human neutrophils2003In: APMIS, ISSN 0903-4641, Vol. 111, no 10, p. 963-968Article in journal (Refereed)
    Abstract [en]

    The objective was to study the expression of inducible nitric oxide synthase (NOS II) in and NO production by human blood neutrophils and in in vivo exudated neutrophils. Cellular expression of NOS II was evaluated by flow cytometry in whole blood, in isolated blood neutrophils, and in neutrophils obtained by exudation in vivo into skin chambers. Neutrophil NOS II was also demonstrated by Western blotting. Uptake of 3H-labelled L-arginine was studied in vitro and NOS activity measured in a whole cell assay by the conversion of 3H-arginine to 3H-citrulline. In contrast to unseparated blood cells, NOS II was demonstrable both in isolated blood neutrophils and exudated cells. The failure to detect NOS II by flow cytometry in whole blood cells thus proved to be due to the quenching effect of hemoglobin. Western blotting revealed a 130 kD band corresponding to NOS II in isolated blood neutrophils, but detection was dependent on diisopropylfluorophosphate for proteinase inhibition. L-arginine was taken up by neutrophils, but enzymatic activity could not be demonstrated. We conclude that human neutrophils constitutively express NOS II, but that its demonstration by FITC-labelling is inhibited by hemoglobin-mediated quenching in whole blood samples.

  • 17.
    Coenen, Marieke J H
    et al.
    Radboud University Nijmegen.
    Enevold, Christian
    University of Copenhagen Hospital.
    Barrera, Pilar
    Radboud University Nijmegen.
    Schijvenaars, Mascha M V A P
    Radboud University Nijmegen.
    J M Toonen, Erik
    Radboud University Nijmegen.
    Scheffer, Hans
    Radboud University Nijmegen.
    Padyukov, Leonid
    Karolinska Institute.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Klareskog, Lars
    Karolinska Institute.
    Barton, Anne
    University of Manchester.
    Kievit, Wietske
    Ziekenhuis Gelderse Vallei.
    Jansen, Tim L
    Medical Centre Leeuwarden.
    Swinkels, Dorine
    Radboud University Nijmegen.
    van Riel, Piet L C M
    Radboud University Nijmegen.
    Franke, Barbara
    Radboud University Nijmegen.
    Bendtzen, Klaus
    University of Copenhagen Hospital.
    Radstake, Timothy R D J
    Radboud University Nijmegen.
    Genetic Variants in Toll-Like Receptors Are Not Associated with Rheumatoid Arthritis Susceptibility or Anti-Tumour Necrosis Factor Treatment Outcome2010In: PLOS ONE, ISSN 1932-6203, Vol. 5, no 12Article in journal (Refereed)
    Abstract [en]

    Background: Several studies point to a role of Toll-like receptors (TLRs) in the development of rheumatoid arthritis (RA). We investigated if genetic variants in TLR genes are associated with RA and response to tumour necrosis factor blocking (anti-TNF) medication. Methodology and Principal Findings: 22 single nucleotide polymorphisms (SNPs) in seven TLR genes were genotyped in a Dutch cohort consisting of 378 RA patients and 294 controls. Significantly associated variants were investigated in replication cohorts from The Netherlands, United Kingdom and Sweden (2877 RA patients and 2025 controls). 182 of the Dutch patients were treated with anti-TNF medication. Using these patients and a replication cohort (269 Swedish patients) we analysed if genetic variants in TLR genes were associated with anti-TNF outcome. In the discovery phase of the study we found a significant association of SNPs rs2072493 in TLR5 and rs3853839 in TLR7 with RA disease susceptibility. Meta-analysis of discovery and replication cohorts did not confirm these findings. SNP rs2072493 in TLR5 was associated with anti-TNF outcome in the Dutch but not in the Swedish population. Conclusion: We conclude that genetic variants in TLRs do not play a major role in susceptibility for developing RA nor in anti-TNF treatment outcome in a Caucasian population.

  • 18.
    Cöster, Lars
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Kendall, Sally
    Multidisciplinary Pain Centre Copenhagen University Hospital, Copenhagen, Denmark.
    Gerdle, Björn
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Henriksson, Chris
    Department of Clinical and Experimental Medicine Linköping University.
    Henriksson, Karl-Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Chronic widespread musculoskeletal pain - A comparison of those who meet criteria for fibromyalgia and those who do not2008In: European Journal of Pain, ISSN 1090-3801, E-ISSN 1532-2149, Vol. 12, no 5, p. 600-610Article in journal (Refereed)
    Abstract [en]

    Fibromyalgia is currently classified as chronic widespread pain with widespread allodynia to pressure pain. There are few data describing pain characteristics, quality of life, consequences for daily living, and psychosocial status in patients who meet the classification criteria for fibromyalgia proposed by the American College of Rheumatology compared with patients with chronic widespread pain but not widespread allodynia. This study used a randomly selected sample from the general population. A postal questionnaire and a pain mannequin were sent to 9952 people. The response rate was 76.7%. The pain drawings showed that 345 people had widespread pain, that is, they noted pain in all four extremities and axially. Clinical examination, which included a manual tender point examination, was performed in 125 subjects. These people answered commonly used questionnaires on pain, quality of life, coping strategies, depression, and anxiety. Compared with chronic widespread pain without widespread allodynia, fibromyalgia was associated with more severe symptoms/consequences for daily life and higher pain severity. Similar coping strategies were found. Chronic widespread pain without widespread allodynia to pressure pain was found in 4.5% in the population and fibromyalgia in 2.5%. © 2007 European Federation of Chapters of the International Association for the Study of Pain.

  • 19.
    Dahle, Charlotte
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Åberg, A K
    Örebro.
    Jalal, A
    Örebro.
    Olcén, Per
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Microbiology.
    Methods of choice for diagnostic antinuclear antibody (ANA) screening: Benefit of adding antigen-specific assays to immunofluorescence microscopy2004In: Journal of Autoimmunity, ISSN 0896-8411, E-ISSN 1095-9157, Vol. 22, no 3, p. 241-248Article in journal (Refereed)
    Abstract [en]

    Objectives. To evaluate and compare the performances of three enzyme-immunoassays (EIAs) and a double radial immunodiffusion (DRID) test in addition to immunofluorescence (IF) microscopy for routine laboratory screening of patient sera sent for antinuclear antibody (ANA) analysis. Methods. 3079 consecutive patient sera sent for routine testing of ANA were analysed by IF microscopy on HEp-2 cells (IF-ANA), three different ANA-EIAs, and a DRID test for antibodies against extractable nuclear antigens. The IF-ANA and DRID tests were regarded as reference methods. Results. By IF-ANA and/or DRID, 375 sera (12%) turned out ANA-positive. A further 171 sera (6%) were positive by EIA, but could not be confirmed either by IF microscopy or DRID. 32 of the 375 ANA-positive (9%) sera were negative by IF microscopy, but had precipitating antibodies against Ro/SS-A (52 and/or 60 kD). Conclusions. Different assays for ANA analysis give overlapping results to a certain extent, but are by no means interchangeable. Thus, different ANA tests reflect different aspects of these autoantibodies. The diagnostic utility of ANA testing still mainly refers to IF-microscopy and precipitin tests. IF-ANA should not be abandoned as the golden standard in clinical routine, until diagnostic and classification criteria for systemic lupus erythematosus and other systemic inflammatory autoimmune diseases have been revised. However, in addition we strongly advocate that a specific test for anti-Ro/SS-A antibodies is always included.

  • 20.
    Dahlström, Örjan
    et al.
    Linköping University, Department of Behavioural Sciences and Learning. Linköping University, Faculty of Arts and Sciences.
    Timpka, Toomas
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Prognostic components and predictive modelling of prognosis in early RAManuscript (preprint) (Other academic)
    Abstract [en]

    Introduction: There is a need for tools that are easy to use in clinical practice supporting decision making upon treatment in early rheumatoid arthritis (RA). Aim: The aim was to identify components of prognosticators in early RA and to identify individual patients with a poor prognosis as early as possible.

    Methods: Two cohorts from the Swedish TIRA project including 320+408 patients with recent onset RA were included in the study. Disease activity was measured by C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and the 28-joint count disease activity score (DAS-28), and by the physicians’ global assessment of disease activity (PGA). Disability was assessed as activity limitation by the Swedish version of the Health Assessment Questionnaire (HAQ) and impairment was reported by pain on a visual analogue scale of 0–100 mm. Serological markers were rheumatoid factor (RF) and anti-CCP. RF was measured at the time for diagnosis, and anti-CCP at the time of diagnosis or at one or some of the follow-ups. If at least one anti-CCP test was positive, the patient was judged to be anti-CCP-positive. Assuming different clinical practice in the different cohorts, two different treatment strategies were assumed based on clinical practice in real-world settings. Principal Component Analysis and Multiple Linear Regression Analysis were used to identify prognosticators. Prediction rules were identified by data-driven approach, controlling for different treatment strategies.

    Results: Progression of disease and disability measures and inflammation measures the first three months after inclusion predicted a considerable part of DAS-28 at the 1-year follow-up. Serological markers had a larger explanatory power for men than for women. Anti-CCP was a significant predictor for men, but not for women. Two versions of rules, one for women and one for men, predicting good or poor prognosis at one year after inclusion were produced by using measures of disability (Health Assessment Questionnaire), DAS-28, relative change in DAS-28 during first three months, sex, and test of anti-CCP. The rules demanded high prognostic specificity but the prognostic sensitivity was moderate.

    Conclusion: A considerable part of DAS-28 at one year after inclusion could be explained by the first 3 months’ progression of disease, disability and inflammation. Anti-CCP was predictive for men but not for women, and needs further investigation. A decision tree predicting poor prognosis among individual early RA-patients showed high specificity and moderate sensitivity on a validationcohort. The medical informatics approach used, controlling for different treatment strategies, yields promising results and further studies will control for more specific differences in treatment strategies, e.g. different DMARDs initiated.

  • 21.
    Enocsson, Helena
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Eloranta, Maija-Leena
    Uppsala Univ, Uppsala, Sweden.
    Ronnblom, Lars
    Uppsala Univ, Uppsala, Sweden.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Interferon-alpha Mediates Suppression of C-Reactive Protein Explanation for Muted C-Reactive Protein Response in Lupus Flares?2009In: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, no 12, p. 3755-3760Article in journal (Refereed)
    Abstract [en]

    Objective. C-reactive protein (CRP) is synthesized by hepatocytes in response to interleukin-6 (IL-6) during inflammation. Despite raised IL-6 levels and extensive systemic inflammation, serum CRP levels remain low during most viral infections and disease flares of systemic lupus erythematosus (SLE). Because both viral infections and SLE are characterized by high levels of interferon-alpha (IFN alpha), the aim of this study was to determine whether this cytokine can inhibit the induction of CRP. Methods. The interference of all 12 IFN alpha subtypes with CRP promoter activity induced by IL-6 and IL-1 beta was studied in a CRP promoter- and luciferase reporter-transfected human hepatoma cell line, Hep-G2. CRIP secretion by primary human hepatocytes was analyzed by enzyme-linked immunosorbent assay. Results. CRP promoter activity was inhibited by all single IFN alpha subtypes, as well as by 2 different mixtures of biologically relevant IFN alpha subtypes. The most prominent effect was seen using a leukocyte-produced mixture of IFN alpha (56% inhibition at 1,000 IU/ml). The inhibitory effect of IFN alpha was confirmed in primary human hepatocytes. CRP promoter inhibition was dose dependent and mediated via the type I IFN receptor. Transferrin production and Hep-G2 proliferation/viability were not affected by IFN alpha. Conclusion. The current study demonstrates that IFN alpha is an inhibitor of CRP promoter activity and CRP secretion. This finding concords with previous observations of up-regulated IFN alpha and a muted CRP response during SLE disease flares. Given the fundamental role of both IFN alpha and CRP in the immune response, our results are of importance for understanding the pathogenesis of SLE and may also contribute to understanding the differences in the CRP response between viral and bacterial infections.

  • 22.
    Eriksson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Andersson, Carina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls2004In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 137, no 3, p. 617-620Article in journal (Refereed)
    Abstract [en]

    Primary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0.52, P = 0.0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.

  • 23.
    Eriksson, Per
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Andersson, Carina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Ekerfelt, Christina
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Sjögren´s syndrome with myalgia is associated with subnormal secretion of cytokines by peripheral blood mononuclear cells.2004In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 31, p. 729-735Article in journal (Refereed)
  • 24.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Jacobsson, L
    Malmö University Hospital.
    Lindell, A
    Skogsfrid Primary Care Centre.
    Nilsson, J-A
    Malmö University Hospital.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Improved outcome in Wegener's granulomatosis and microscopic polyangiitis? A retrospective analysis of 95 cases in two cohorts.2009In: Journal of internal medicine, ISSN 1365-2796, Vol. 265, no 4, p. 496-506Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Mortality rates for Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) have decreased after the introduction of cyclophosphamide. Standardized mortality ratio (SMR) expresses the overall mortality of patients compared with the general population. The aims of this study were to compare survival in an old and a recent cohort of patients with WG and MPA using SMR and to determine predictors for death in both groups combined. DESIGN: Survival analyses were performed by Kaplan-Meier survival curves, SMR and proportional hazards regression models. SETTING: The nephrology and rheumatology clinics at Linköping University Hospital, Sweden. SUBJECTS: All patients diagnosed with WG or MPA in the catchment area during 1978-2005 were divided into two cohorts; patients diagnosed before (n=32, old cohort) and after (n=63, recent cohort) December 31, 1996. RESULTS: The two cohorts differed regarding the proportion of WG (75% vs. 56%, P=0.03) and a tendency for more pronounced kidney involvement in the old cohort: 266 micromol L(-1) (16% dialysis-dependent) vs. 192 micromol L(-1) (5% dialysis-dependent), but were comparable regarding disease severity. SMR at 1 and 5 years were 2.1 (95% CI: 0.43-6.09) and 1.6 (95% CI: 0.6-3.2) in the recent cohort and 5.2 (95% CI: 1.07-15.14) and 2.5 (95% CI: 0.93-5.52) in the old cohort. Five-year survival was 87% and 81%. Serum creatinine, age, end-stage renal disease, diagnosis before 1997 and first relapse were independent predictors for death. CONCLUSION: Patient survival in WG and MPA analysed with SMR may be better than previously believed. Severe renal disease and disease relapse were the major predictors of reduced survival.

  • 25.
    Eriksson, Per
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Sandell, Christina
    Backteman, Karin
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, 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 Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    B lymphocyte subpopulations in Wegeners granulomatosis and microscopic polyangiitis with special reference to CD25+-expressing B cells2009In: in APMIS vol 117, 2009, Vol. 117, p. 116-116Conference paper (Refereed)
    Abstract [en]

    n/a

  • 26.
    Gerdle, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Björk, Jonas
    Competence Centre for Clinical Research Lund University Hospital.
    Cöster, Lars
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Henriksson, Karl-Gösta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine . Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Henriksson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Social and Welfare Studies.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Prevalence of widespread pain and associations with work status: A population study2008In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 9Article in journal (Refereed)
    Abstract [en]

    Background. This population study based on a representative sample from a Swedish county investigates the prevalence, duration, and determinants of widespread pain (WSP) in the population using two constructs and estimates how WSP affects work status. In addition, this study investigates the prevalence of widespread pain and its relationship to pain intensity, gender, age, income, work status, citizenship, civil status, urban residence, and health care seeking. Methods. A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, 18-74 years) in a county (Östergötland) in the southern Sweden. The questionnaire was mailed and followed by two postal reminders when necessary. Results. The participation rate was 76.7% (n = 7637), the non-participants were on the average younger, earned less money, and male. Women had higher prevalences of pain in 10 different predetermined anatomical regions. WSP was generally chronic (90-94%) and depending on definition of WSP the prevalence varied between 4.8-7.4% in the population. Women had significantly higher prevalence of WSP than men and the age effect appeared to be stronger in women than in men. WSP was a significant negative factor - together with age 50-64 years, low annual income, and non-Nordic citizen - for work status in the community and in the group with chronic pain. Chronic pain but not the spreading of pain was related to health care seeking in the population. Conclusion. This study confirms earlier studies that report high prevalences of widespread pain in the population and especially among females and with increasing age. Widespread pain is associated with prominent effects on work status. © 2008 Gerdle et al, licensee BioMed Central Ltd.

  • 27.
    Gerdle, Björn
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Björk, Jonas
    Lunds Universitet.
    Henriksson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Occupational Therapy.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Prevalence of current and chronic pain and their influences upon work and healthcare-seeking: A population study2004In: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 31, no 7, p. 1399-1406Article in journal (Refereed)
    Abstract [en]

    Objective. To investigate the prevalence of current and chronic pain and their relationship to pain intensity, sex, age, income, employment status, citizenship, marital status, urban residence, occupational activity, and healthcare-seeking based on a representative sample from a Swedish county. Methods. A cross-sectional survey using a postal questionnaire was sent to a representative sample (n = 9952) of the target population (284,073 people, age 18-74 yrs) in a county (Östergötland) in southern Sweden. A questionnaire was mailed and followed by 2 postal reminders if necessary. Results. The participation rate was 76.7% (n = 7637), nonparticipants were on average younger, male, and earned less money. The overall point prevalence of pain was 48.9%. The corresponding one-month period prevalence was 63.0%, and pain on several occasions during the previous 3 months was reported by 61.3% of participants. The prevalence of chronic pain (pain > 3 months) was 53.7%. Female sex, age, and sick leave/early retirement were generally of significant importance in the regressions of pain. No sex factor was found in the regressions of pain frequency and pain intensity. Chronic pain - especially frequent and intensive pain - showed clear associations with healthcare-seeking and occupational activity. Conclusion. High prevalence of current pain (48.9%) and chronic pain (53.7%) were found in this community-based study. Being female, older, and on sick leave or early retirement were generally of significant importance in the regressions of pain. Chronic pain showed clear associations with healthcare-seeking and occupational activity, indicating considerable socioeconomic costs.

  • 28.
    Haldorsen, K
    et al.
    University of Bergen.
    Appel, S
    University of Bergen.
    Bruland, O
    Haukeland Hospital.
    Le Hellard, S
    University of Bergen.
    Brun, J G
    University of Bergen.
    Omdal, R
    Stavanger University Hospital.
    Kristjansdottir, G
    Uppsala University.
    Theander, E
    Malmö University Hospital.
    Nordmark, G
    Uppsala University.
    Kvamstrom, M
    Karolinska Institute.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Ronnblom, L
    Uppsala University.
    Wahren-Herlenius, M
    Karolinska Institute.
    Jonsson, R
    University of Bergen.
    I Bolstad, A
    University of Bergen.
    Fc gamma receptor IIA, IIIA and IIIB single nucleotide polymorphisms and Fc gamma receptor IIIB copy number variation: No association with primary Sjogrens syndrome in SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, vol 39, issue , pp 36-362010In: SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, Informa Healthcare , 2010, Vol. 39, p. 36-36Conference paper (Refereed)
    Abstract [en]

    n/a

  • 29.
    Hallert, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Husberg, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Department of Health and Society, Center for Medical Technology Assessment.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Costs, disease and function in recent-onset rheumatoid arthritis - a 3-year-follow-up (the Swedish TIRA-project)2004In: Svenska Läkaresällskapets riksstämma,2004, 2004Conference paper (Refereed)
  • 30.
    Hallert, Eva
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Thyberg, Ingrid
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences.
    Hass, Ursula
    Linköping University, Department of Medical and Health Sciences, Health Technology Assessment. Linköping University, The Institute of Technology.
    Skargren, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Physiotherapy. 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Comparison between women and men with recent onset rheumatoid arthritis of disease activity and functional ability over two years (the TIRA project)2003In: Annals of the rheumatic diseases, ISSN 0003-4967, Vol. 62, p. 667-670Article in journal (Refereed)
    Abstract [en]

    Objective: To describe the course of recent onset rheumatoidarthritis (RA) and to compare consequences of the disease inmen and women.

    Methods: 284 patients with recent onset RA were followed upprospectively for two years from the time of diagnosis. Measuresof disease activity (for example, 28 joint disease activityscore (DAS28), C reactive protein, morning stiffness, physician’sglobal assessment) and function outcome (for example, rangeof movement, hand function, walking time) were determined. Thepatients’ self reported assessment of functional capacity(Health Assessment Questionnaire (HAQ)) and grading of wellbeingand pain (visual analogue scale) were registered. Changes overtime and differences between men and women were evaluated.

    Results: Improvements were seen for all variables within thefirst three months. Disease activity then remained unchanged.Function variables followed the same pattern during the firstyear, but then tended to worsen. HAQ scores were similar atbaseline, but significantly worse in women than in men at theone and two year follow ups.

    Conclusions: Disease activity was well managed and had improvedsubstantially after two years, whereas function seemed slowlyto deteriorate. Although disease variables were similar formen and women, functional ability (HAQ) had a less favourablecourse in women.

  • 31. Johansson, AG
    et al.
    Sundqvist, Tommy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    IgG immune complex binding to and activation of liver cells.1999In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 121, p. 329-336Article in journal (Refereed)
  • 32.
    Johansson, AG
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Sundqvist, Tommy
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Medical Microbiology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    IgG immune complex binding to and activation of liver cells. An in vitro study with IgG immune complexes, Kupffer cells, sinusoidal endothelial cells and hepatocytes2000In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 121, no 4, p. 329-336Article in journal (Refereed)
    Abstract [en]

    Background/Aims: The aim was to study IgG immune complex (IC) binding to isolated hepatocytes, Kupffer cells (KCs) and sinusoidal endothelial cells (SECs). Further, we wished to analyze the capacity of IgG ICs to induce release of reactive oxygen metabolites by the IC-binding liver cells. Methods: ICs were formed between 125I-tyramine-cellobiose-labelled dinitrophenyl-conjugated human serum albumin (125I-TC-DNP10HSA) and polyclonal rabbit IgG antibodies. Binding of ICs to different rat liver cells in suspension was studied at 4░C. Production of reactive oxygen metabolites was measured by luminol-enhanced chemiluminescence at 37░C. Results: IgG mediated binding of 125I-TC-DNP10HSA to both KCs and SECs, but not to hepatocytes. The binding showed saturation kinetics and was blocked by an excess of unlabelled IgG-ICs. IgG-ICs activated KCs, but not SECs, to a chemiluminescence response. Conclusions: Both KCs and SECs bind IgG-ICs in vitro, probably via Fc receptor interaction. IgG-ICs activate KCs to produce reactive oxygen metabolites. The binding of IgG-ICs to isolated hepatocytes is small.

  • 33.
    Kanmert, Daniel
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Science & Engineering.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Enander, Karin
    Linköping University, Department of Physics, Chemistry and Biology, Molecular Physics. Linköping University, Faculty of Science & Engineering.
    Designed Surface with Tunable IgG Density as an in Vitro Model for Immune Complex Mediated Stimulation of Leukocytes2010In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 26, no 5, p. 3493-3497Article in journal (Refereed)
    Abstract [en]

    We present the design of an in vitro for immune-complex-mediated stimulation of leukocytes and its functional characteristics with respect to monocyte adhesion. The model was based on orientation-controlled immobilization of a humanized IgG1 monoclonal antibody (rituximab) via its interaction with a biotinylated peptide epitope derived from the CD20 marker. The peptide was linked to neutravidin covalently attached to it mixed self-assembled monolayer of carboxyl- and methoxy-terminated oligo(ethylene glycol) alkane thiolates on gold. The surface adhesion propensity of human monocytes (cell line U917) was highly dependent on the lateral IgG density and indicated that there exists a distance between IgG-Fc on the surface where interactions with Fc gamma receptors are optimal. This well-defined platform allows for a careful control of the size and orientation of artificial IgG immune complexes, it is easily made compatible with, for example, cellular imaging, and it will become useful for in vitro studies on the importance of Fc gamma receptor interactions in chronic immune-mediated diseases.

  • 34.
    Kastbom, Alf
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Autoantibodies and genetic variation in rheumatoid arthritis: aspects on susceptibility and disease course2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and subsequent destruction of synovial joints. Although its causes remain largely unknown, a substantial genetic contribution is known to exist. During the last decades the benefits of early aggressive treatment have become evident, and more potent therapeutic options have become available. These advances have increased the demands for rapid accurate diagnosis and prognostic markers of disease course and therapy response.

    The ‘rheumatoid factor’ (RF) has long been used as a diagnostic and prognostic marker of RA. In this thesis, the utility of measuring antibodies to cyclic citrullinated peptides (CCP) was investigated. In a population-based arthritis incidence study, 69 very early arthritis patients (symptom duration < 3 months) were identified. The anti-CCP test, performed at baseline and related to diagnosis at the 2-year follow-up, had a diagnostic specificity for RA of 96% and a sensitivity of 44%, both of which were superior to RF. In a prospective cohort of 242 incident cases of RA (symptom duration < 1 year), 64% of the patients tested positive for anti-CCP at baseline (equal to RF). Despite receiving more active anti-rheumatic therapy, the anti-CCP-positive patients had a more aggressive disease course during 3 years as compared to those testing negative.

    The 158VV genotype of Fcγ Receptor type IIIA (FcγRIIIA), which binds IgG with higher affinity than 158FF, was associated with an increased susceptibility to RA in men, but not in women. Previous studies report conflicting results, and none stratified according to gender. The 158V/F polymorphism of FcγRIIIA was not found to influence outcome of anti-tumour necrosis factor therapy in 282 RA patients, contradicting hints from previous studies. Genetic variation in proteins of the inflammasome, an interleukin-1 (IL-1) regulating intracellular protein complex, is associated with rare autoinflammatory conditions and possibly with Crohn’s disease. In this first study on genetic variation of the inflammasome in RA, we describe a compound polymorphism of the genes CIAS1 and TUCAN that associates both with susceptibility to RA and to the severity of the disease. Hypothetically, these genes may identify a subgroup of RA patients that would benefit from anti-IL-1 therapy.

    This thesis work emphasizes the benefits of testing for anti-CCP in the diagnosis and outcome prediction in early arthritis. FcγRIIIA genotype is likely to affect RA susceptibility and further work should apply a gender perspective. Inflammasome genetics may influence the risk of developing RA. Additional studies are warranted to settle whether it also identifies a subgroup of RA patients benefiting from IL-1 targeted therapy.

    List of papers
    1. Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity
    Open this publication in new window or tab >>Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity
    Show others...
    2004 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, Vol. 33, no 3, p. 185-188Article in journal (Refereed) Published
    Abstract [en]

    Objective: To measure serum levels of antibodies against cyclic citrullinated peptide (anti-CCP antibodies) and serum cartilage oligomeric matrix protein (COMP) in patients with early joint inflammation, and to study the correlation of these two tests with clinical measurements.

    Methods: Adult patients with recent-onset arthritis, of <3 months' duration, were referred from primary healthcare centres to rheumatologists. Serum levels of anti-CCP antibodies and COMP at baseline were analysed by enzyme immunoassay (EIA) and compared with clinical baseline data.

    Results: Sixty-nine patients were included. The specificity of the anti-CCP antibody test for RA was 96%, and the sensitivity was 44%. There was a significant difference between the four diagnosis groups in the anti-CCP antibody test, probability (p)<0.001, whereas no significant differences were found concerning COMP. The baseline serum COMP test correlated with age (p=0.0001), joint score for swollen joints (p=0.02), and C-reactive protein (CRP) (p=0.02).

    Conclusion: This study confirms the high diagnostic specificity of anti-CCP antibodies for rheumatoid arthritis (RA) in a prospective population-based study of very early arthritis. Raised serum COMP levels were common in all diagnosis groups in this series, indicating cartilage involvement in both self-limiting and non-erosive disease.

    Keywords
    anti-CCP antibodies, COMP, rheumatoid arthritis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14376 (URN)10.1080/03009740310004856 (DOI)
    Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31
    2. Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)
    Open this publication in new window or tab >>Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)
    2004 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, Vol. 63, no 9, p. 1085-1089Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To evaluate the diagnostic sensitivity of antibodies to cyclic citrullinated peptide (CCP) in recent onset rheumatoid arthritis (RA) at diagnosis and 3 years later, and to evaluate anti-CCP antibody as a predictor of the disease course during 3 years.

    Methods: 242 patients with recent onset (≤ 1 year) RA were followed up regularly during 3 years after inclusion in the Swedish multicentre study "TIRA" 1996-98. Anti-CCP antibodies were analysed by an enzyme immunoassay (EIA). Rheumatoid factors (RFs) were analysed by latex agglutination and two isotype-specific (IgM and IgA) EIAs. Disease activity was assessed by plasma CRP, ESR, 28 joint disease activity score, and the physician's global assessment of disease activity. Functional ability was evaluated by the Health Assessment Questionnaire.

    Results: Overall, the diagnostic sensitivity of anti-CCP antibodies was 64% and the proportion of positive tests increased with the number of fulfilled classification criteria according to the American College of Rheumatology. The anti-CCP antibody results correlated with RF, but were better than RF as predictor of a more aggressive disease course. After 3 years 5/97 patients had changed anti-CCP status: 2 from negative to positive and 3 from positive to negative. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% Cl 34 to 228 U/ml).

    Conclusion: The anti-CCP antibody assay has a similar diagnostic sensitivity to that of RF in early RA, but is better as a predictor of the disease course over 3 years. Although the mean serum level declines, anti-CCP antibody positivity remains essentially unaltered 3 years after diagnosis and start of antirheumatic treatment.

    Keywords
    anti-CCP antibody, rheumatoid factor, early rheumatoid arthritis, inflammation, disease course
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14377 (URN)10.1136/ard.2003.016808 (DOI)
    Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31
    3. The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid arthritis: increased susceptibility and severity in male patients (the Swedish TIRA project)
    Open this publication in new window or tab >>The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid arthritis: increased susceptibility and severity in male patients (the Swedish TIRA project)
    2005 (English)In: Rheumatology, ISSN 1462-0324, Vol. 44, no 10, p. 1294-1298Article in journal (Refereed) Published
    Abstract [en]

    Objectives. To evaluate the influence of Fc receptor IIIA (FcRIIIA) 158V/F polymorphism on susceptibility and disease severity in early rheumatoid arthritis (RA).

    Methods. In 181 Swedish patients (128 women, 53 men) with RA of recent onset, disease and disability variables such as erythrocyte sedimentation rate, 28-joint disease activity score (DAS28) and health assessment questionnaire (HAQ) scores were monitored regularly during 3 yr. Three hundred and sixty-two controls were recruited from the same geographical area as the patients. FcRIIIA genotyping was performed using denaturing high-performance liquid chromatography.

    Results. In all RA patients, FcRIIIA-158VV was significantly over-represented compared with controls [odds ratio (OR) 1.9, 95% confidence interval (CI) 1.01–3.5, P<0.05]. After stratifying for sex, the difference remained in the male population (OR 3.2, 95%CI 1.03–11, P<0.05) but disappeared among women (OR 1.4, 95%CI 0.7–3.1, P=0.4). In addition, 158VV patients were more likely to exhibit early joint erosions (OR 6.1, 95%CI 1.4–28, P<0.01). At baseline, patients with different FcRIIIA genotypes did not differ with respect to measures of disease activity or functional ability. Thereafter, in male patients with at least one V allele the mean DAS28 and HAQ scores were higher compared with 158FF. In contrast, female patients with at least one 158V allele displayed lower mean DAS28 and HAQ scores compared with those with 158FF.

    Conclusions. In a male population, the FcRIIIA-158VV genotype is associated with an increased risk of developing RA, and the 158V allele with more severe disease in early RA.

    Keywords
    Disease course, Early rheumatoid arthritis, Fc receptor, Single-nucleotide polymorphism
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14378 (URN)10.1093/rheumatology/kei010 (DOI)
    Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31
    4. Fcγ receptor type IIIA genotype and response to tumor necrosis factor alpha-blocking agents in patients with rheumatoid arthritis
    Open this publication in new window or tab >>Fcγ receptor type IIIA genotype and response to tumor necrosis factor alpha-blocking agents in patients with rheumatoid arthritis
    Show others...
    2007 (English)In: Arthritis and Rheumatism, ISSN 0004-3591, Vol. 56, no 2, p. 448-452Article in journal (Refereed) Published
    Abstract [en]

    Objective: To determine whether a functional single-nucleotide polymorphism in the gene encoding Fc receptor type IIIA (FcRIIIA) correlates with the response to treatment with tumor necrosis factor inhibitors in rheumatoid arthritis (RA).

    Methods: The study population comprised 282 Swedish patients with RA in whom the therapeutic efficacy of conventional disease-modifying antirheumatic drugs had been insufficient. Infliximab or etanercept treatment was initiated, and patients were evaluated after 3 months, using the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 or the European League Against Rheumatism (EULAR) criteria. The chi-square test was used to compare response rates across FcRIIIA genotypes.

    Results: No differences in genotype distribution were observed among nonresponders compared with ACR20 responders (P = 0.80), ACR50 responders (P = 0.56), or ACR70 responders (P = 0.91). Similar results were observed when analyzing infliximab and etanercept separately or when using the EULAR response criteria.

    Conclusion: Unlike the findings of a previous study, the results of the current study suggest that the 158V/F polymorphism of FcRIIIA is very unlikely to influence the clinical efficacy of infliximab or etanercept in patients with RA.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14379 (URN)10.1002/art.22390 (DOI)
    Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31
    5. Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project)
    Open this publication in new window or tab >>Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (the Swedish TIRA project)
    Show others...
    2008 (English)In: Rheumatology, ISSN 1462-0324, Vol. 47, no 4, p. 415-417Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The genetic background to RA is incompletely understood.As new cytokine-targeted therapies emerge, early predictorsof disease severity are becoming increasingly important. Theinflammasomes are essential regulators of cytokine production.We investigated whether two polymorphisms in the genes encodingcryopyrin (CIAS1) and TUCAN (CARD8) influence susceptibilityand disease course in RA.

    Methods: Genotype frequencies were assessed in 174 Swedish patientswith early RA and 360 population-based controls without rheumaticdisease. Genotypes were categorized according to the presence(+) or absence (–) of two wild-type alleles and comparedbetween patients and controls. In the RA patients, antibodiestowards cyclic citrullinated peptides (anti-CCP) and the ‘sharedepitope’ (SE) were assessed, and medication and measuresof disease activity were monitored regularly during 3 yrs.

    Results: The combination of CIAS1/TUCAN/–, ascompared with CIAS1/TUCAN +/+, was significantly more commonamong patients than in controls [odds ratio (OR) 2.2, 95% CI1.03–4.6]. This association was strengthened when patientswere divided into anti-CCP+ [OR 2.8 (1.1–6.7)] or presenceof 1 SE copy [OR 2.8 (1.3–6.2)]. At most time-points duringthe 3-yr follow-up, patients with CIAS1/TUCAN/–showed significantly higher disease activity. Furthermore, CIAS1/TUCAN/– patients proved to be much more likely to receiveTNF-blocking therapy [relative risk 20 (2.6–149)].

    Conclusions: Compound polymorphisms in CIAS1 and TUCAN associatewith RA susceptibility and severity. The cryopyrin inflammasomeneeds further attention regarding a possible aetiopathogeneticconnection with RA.

    Keywords
    Disease course, Genetics, Inflammasome, Rheumatoid arthritis
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-14380 (URN)10.1093/rheumatology/kem372 (DOI)
    Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31Bibliographically approved
  • 35.
    Kastbom, Alf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Bratt, Johan
    Karolinska University Hospital Huddinge and Karolinska Institutet, Stockholm, Sweden.
    Ernestam, Sofia
    Karolinska University Hospital Huddinge and Karolinska Institutet, Stockholm, Sweden.
    Lampa, Jon
    Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Padyukov, Leonid
    Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Fcγ receptor type IIIA genotype and response to tumor necrosis factor alpha-blocking agents in patients with rheumatoid arthritis2007In: Arthritis and Rheumatism, ISSN 0004-3591, Vol. 56, no 2, p. 448-452Article in journal (Refereed)
    Abstract [en]

    Objective: To determine whether a functional single-nucleotide polymorphism in the gene encoding Fc receptor type IIIA (FcRIIIA) correlates with the response to treatment with tumor necrosis factor inhibitors in rheumatoid arthritis (RA).

    Methods: The study population comprised 282 Swedish patients with RA in whom the therapeutic efficacy of conventional disease-modifying antirheumatic drugs had been insufficient. Infliximab or etanercept treatment was initiated, and patients were evaluated after 3 months, using the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 or the European League Against Rheumatism (EULAR) criteria. The chi-square test was used to compare response rates across FcRIIIA genotypes.

    Results: No differences in genotype distribution were observed among nonresponders compared with ACR20 responders (P = 0.80), ACR50 responders (P = 0.56), or ACR70 responders (P = 0.91). Similar results were observed when analyzing infliximab and etanercept separately or when using the EULAR response criteria.

    Conclusion: Unlike the findings of a previous study, the results of the current study suggest that the 158V/F polymorphism of FcRIIIA is very unlikely to influence the clinical efficacy of infliximab or etanercept in patients with RA.

  • 36.
    Kastbom, Alf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Johansson, Martin
    Umeå University.
    Verma, Deepti
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Söderkvist, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Rantapaa-Dahlqvist, Solbritt
    Umeå University.
    CARD8 p.C10X polymorphism is associated with inflammatory activity in early rheumatoid arthritis2010In: ANNALS OF THE RHEUMATIC DISEASES, ISSN 0003-4967, Vol. 69, no 4, p. 723-726Article in journal (Refereed)
    Abstract [en]

    Objectives CARD8 and NLRP3 are constituents of the inflammasome which regulates interleukin 1 beta production. The influence of polymorphisms in CARD8 and NLRP3 on rheumatoid arthritis (RA) susceptibility and severity were evaluated. Methods CARD8 p.C10X and NLRP3 p.Q705K genotypes were assessed in andgt;500 controls and patients with early RA from northern Sweden. The patients were monitored regularly over a 2-year period. The 28-joint disease activity score (DAS28) and its separate components were compared across genotypes. Results Patients with one or more variant alleles in CARD8 (CARD8-X) had increased DAS28, tender joint count and erythrocyte sedimentation rate during the 2-year follow-up period despite receiving disease-modifying antirheumatic drugs to a greater extent. CARD8-X was significantly over-represented among patients who received anti-tumour necrosis factor therapy during the first 2 years. CARD8 and NLRP3 genotypes did not influence radiological joint damage and were not associated with an increased susceptibility. Conclusions Carriage of CARD8-X is associated with a worse disease course in early RA.

  • 37.
    Kastbom, Alf
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Strandberg, Gunnar
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Lindroos, Annette
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Anti-CCP antibody test predicts the disease course during 3 years in early rheumatoid arthritis (the Swedish TIRA project)2004In: Annals of the Rheumatic Diseases, ISSN 0003-4967, Vol. 63, no 9, p. 1085-1089Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate the diagnostic sensitivity of antibodies to cyclic citrullinated peptide (CCP) in recent onset rheumatoid arthritis (RA) at diagnosis and 3 years later, and to evaluate anti-CCP antibody as a predictor of the disease course during 3 years.

    Methods: 242 patients with recent onset (≤ 1 year) RA were followed up regularly during 3 years after inclusion in the Swedish multicentre study "TIRA" 1996-98. Anti-CCP antibodies were analysed by an enzyme immunoassay (EIA). Rheumatoid factors (RFs) were analysed by latex agglutination and two isotype-specific (IgM and IgA) EIAs. Disease activity was assessed by plasma CRP, ESR, 28 joint disease activity score, and the physician's global assessment of disease activity. Functional ability was evaluated by the Health Assessment Questionnaire.

    Results: Overall, the diagnostic sensitivity of anti-CCP antibodies was 64% and the proportion of positive tests increased with the number of fulfilled classification criteria according to the American College of Rheumatology. The anti-CCP antibody results correlated with RF, but were better than RF as predictor of a more aggressive disease course. After 3 years 5/97 patients had changed anti-CCP status: 2 from negative to positive and 3 from positive to negative. The mean level of anti-CCP antibodies declined by 131 U/ml during the 3 year follow up (95% Cl 34 to 228 U/ml).

    Conclusion: The anti-CCP antibody assay has a similar diagnostic sensitivity to that of RF in early RA, but is better as a predictor of the disease course over 3 years. Although the mean serum level declines, anti-CCP antibody positivity remains essentially unaltered 3 years after diagnosis and start of antirheumatic treatment.

  • 38. Lindblad, S
    et al.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Nordmark, B
    Teleman, A
    Uddhammar, A
    Vestberg, M
    Vården av nydebuterad reumatoid artrit kan förbättras. 1999In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 96, p. 2493-2496Article in journal (Other (popular science, discussion, etc.))
  • 39.
    Lindström, FD
    et al.
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Lundström, Inger
    Linköping University, Department of Neuroscience and Locomotion, Dental Surgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Oral Surgery UHL.
    α1 Antitrypsin deficiency in a patient with systemic vasculitis and primary Sjögren's syndrome2002In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 61, no 10, p. 945-946Article in journal (Other academic)
    Abstract [en]

    [No abstract available]

  • 40.
    Locht, H
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Kihlström, Erik
    Linköping University, Faculty of Health Sciences. Linköping University, Department of health and environment. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Microbiology.
    Anti-lactoferrin antibodies and other types of anti-neutrophil cytoplasmic antibodies (ANCA) in reactive arthritis and ankylosing spondylitis. 1999In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 117, p. 568-573Article in journal (Refereed)
  • 41. Locht, H
    et al.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Wiik, A
    Characterisation of autoantibodies to neutrophil granule constituents among patients with reactive arthritis, rheumatoid arthritis, and ulcerative colitis.2000In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 59, p. 898-903Article in journal (Refereed)
  • 42.
    Lund, Eva
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Radio Physics.
    Kendall, Sally
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Rehabilitation Medicine. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Janerot-Sjöberg, Birgitta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Care, Clinical Physiology. Östergötlands Läns Landsting, Heart Centre, Department of Clinical Physiology.
    Bengtsson, Ann
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Muscle metabolism in fibromyalgia studied by P-31 magnetic resonance spectroscopy during aerobic and anaerobic exercise2003In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 32, no 3, p. 138-145Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate mechanisms underlying the reduced work capacity of fibromyalgia (FM) patients were compared to healthy controls at specified workloads, using P-31 magnetic resonance spectroscopy (MRS). Methods: The forearm flexor muscle group was examined with MRS at rest, at sub maximal and at maximal controlled dynamic work as well as at maximal isometric contraction. Aerobic fitness was determined by bicycle ergonometry. Results: Metabolite concentrations and muscle pH were similar for patients and controls at lower workloads. At maximal dynamic and static contractions the concentration of inorganic phosphate was lower and at static contractions the pH decrease was smaller in patients. The performed work by patients was only 50% compared to controls and the patients experienced more pain. Maximal oxygen uptake was lower in the fibromyalgia group. Expired gas-analysis in this group showed ventilatory equivalents at similar relative levels of maximal work capacity. Conclusion: Fibromyalgia patients seem to utilise less of the energy rich phosphorous metabolites at maximal work despite pH reduction. They seemed to be less aerobic fitted and reached the anaerobic threshold earlier than the controls.

  • 43.
    Martinsson, Klara
    et al.
    Linköping University, Department of Clinical and Experimental Medicine. 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, Centre for Medicine, Department of Rheumatology in Östergötland.
    Mousavi, Seyed Ali
    Rikshospital University Hospital, Oslo.
    Berg, Trond
    University of Oslo.
    Jönsson, Jan-Ingvar
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Hematology . Linköping University, Faculty of Health Sciences.
    Hultman, Per
    Linköping University, Department of Clinical and Experimental Medicine, Molecular and Immunological Pathology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Pathology and Clinical Genetics.
    Deficiency of Activating Fc gamma-Receptors Reduces Hepatic Clearance and Deposition of IC and Increases CIC Levels in Mercury-Induced Autoimmunity2010In: PLOS ONE, ISSN 1932-6203, Vol. 5, no 10Article in journal (Refereed)
    Abstract [en]

    Background: Inorganic mercury (Hg) induces a T-cell dependent, systemic autoimmune condition (HgIA) where activating Fc gamma-receptors (Fc gamma Rs) are important for the induction. In this study we examined the influence of activating Fc gamma Rs on circulating levels and organ localization of immune complexes (IC) in HgIA. Methods and Principal Findings: Mercury treated BALB/c wt mice showed a significant but modest increase of circulating IC (CIC) from day 12 until day 18 and day 35 for IgG2a- and IgG1- CIC, respectively. Mercury-treated mice lacking the transmembrane gamma-chain of activating Fc gamma Rs (FcR gamma(-/-)) had significantly higher CIC levels of both IgG1-CIC and IgG2a-CIC than wt mice during the treatment course. The hepatic uptake of preformed CIC was significantly more efficient in wt mice compared to Fc gamma R-/- mice, but also development of extrahepatic tissue IC deposits was delayed in FcR gamma(-/-) mice. After 35 days of Hg treatment the proportion of immune deposits, as well as the amounts was significantly reduced in vessel FcR gamma(-/-) mice compared to wt mice. Conclusions: We conclude that mice lacking functional activating Fc gamma Rs respond to Hg with increased levels and altered quality of CIC compared with wt mice. Lack of functional activating Fc gamma Rs delayed the elimination of CIC, but also significantly reduced extrahepatic tissue localization of CIC.

  • 44.
    Mathsson, L.
    et al.
    Uppsala University.
    Åhlin, E.
    Uppsala University.
    Sjöwall, Christoffer
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Rönnelid, J.
    Uppsala University.
    Cytokine induction by circulating immune complexes and signs of in-vivo complement activation in systemic lupus erythematosus are associated with the occurrence of anti-Sjögren's syndrome A antibodies2007In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 147, no 3, p. 513-520Article in journal (Refereed)
    Abstract [en]

    Circulating immune complexes (IC) and levels of IC-induced cytokines have been correlated with complement activation and autoantibody profiles in systemic lupus erythematosus (SLE). SLE sera were analysed concerning levels of immune complexes (IC), classical complement function and different antinuclear and anti-C-reactive protein (CRP) autoantibodies. Blood mononuclear cells from healthy donors were stimulated with isolated IC and production of interleukin (IL)-10, IL-6 and IL-12p40 was measured. Functional experiments revealed that increased levels of IC-induced cytokines were associated with both increased classical complement activation and the occurrence of anti-Sjögren's syndrome A (SSA) and anti-SSB but not other autoantibodies. Biochemical measurement of circulating IC showed that the degree of complement activation and the occurrence of anti-SSA were synergistically associated with levels of circulating IC in SLE sera, as complement activation was a prerequisite for the enhancing effect of anti-SSA. Anti-CRP was associated with complement activation, but not with other autoantibodies. Our results indicate that anti-SSA and possibly anti-SSB antibodies influence IC formation and subsequent IC-induced cytokine induction, and that they thereby participate in the inflammatory process in active SLE.

  • 45.
    Matthiesen, Leif
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Berg, Göran
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Surgery in Östergötland.
    Ernerudh, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Immunology and Transfusion Medicine.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    A prospective study on the occurrence of autoantibodies in low-risk pregnancies. 1999In: European Journal of Obstetrics, Gynecology, and Reproductive Biology, ISSN 0301-2115, E-ISSN 1872-7654, Vol. 83, p. 21-26Article in journal (Refereed)
  • 46.
    Nordmark, G
    et al.
    Uppsala University.
    Kristjansdottir, G
    Uppsala University.
    Theander, E
    Malmö University Hospital.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Brun, J G
    Haukeland Hospital.
    Wang, C
    Uppsala University.
    Padyukov, L
    Karolinska University Hospital.
    Truedsson, L
    Lund University.
    Alm, G
    Swedish University of Agriculture Science.
    Eloranta, M-L
    Uppsala University.
    Jonsson, R
    Haukeland Hospital.
    Ronnblom, L
    Uppsala University.
    Syvanen, A-C
    Uppsala University.
    Additive effects of the major risk alleles of IRF5 and STAT4 in primary Sjogrens syndrome2009In: GENES AND IMMUNITY, ISSN 1466-4879, Vol. 10, no 1, p. 68-76Article in journal (Refereed)
    Abstract [en]

    Primary Sjogrens syndrome (SS) shares many features with systemic lupus erythematosus (SLE). Here we investigated the association of the three major polymorphisms in IRF5 and STAT4 found to be associated with SLE, in patients from Sweden and Norway with primary SS. These polymorphisms are a 5-bp CGGGG indel in the promoter of IRF5, the single nucleotide polymorphism (SNP) rs10488631 downstream of IRF5 and the STAT4 SNP rs7582694, which tags the major risk haplotype of STAT4. We observed strong signals for association between all three polymorphisms and primary SS, with odds ratios (ORs) > 1.4 and P-values < 0.01. We also found a strong additive effect of the three risk alleles of IRF5 and STAT4 with an overall significance between the number of risk alleles and primary SS of P = 2.5 x 10(-9). The OR for primary SS increased in an additive manner, with an average increase in OR of 1.78. For carriers of two risk alleles, the OR for primary SS is 1.43, whereas carriers of five risk alleles have an OR of 6.78. IRF5 and STAT4 are components of the type I IFN system, and our findings emphasize the importance of this system in the etiopathogenesis of primary SS.

  • 47.
    Nordmark, Gunnel
    et al.
    University Uppsala Hospital.
    Kristjansdotti, Gudlaug
    Uppsala University.
    Theander, Elke
    Lund University.
    Appel, Silke
    University of Bergen.
    Eriksson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Vasaitis, Lilian
    University Uppsala Hospital.
    Wahren-Herlenius, Marie
    Karolinska Institute.
    Omdal, Roald
    University of Bergen.
    Ronnblom, Lars
    University Uppsala Hospital.
    Jonsson, Roland
    Uppsala University.
    GENE VARIANTS IN FAM167A-BLK AND TNFSF4 ARE ASSOCIATED WITH PRIMARY SJOGRENS SYNDROME in SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, vol 39, issue , pp 32-322010In: SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, Informa Healthcare , 2010, Vol. 39, p. 32-32Conference paper (Refereed)
    Abstract [en]

    n/a

  • 48.
    Rönnelid, Johan
    et al.
    Uppsala.
    Klareskog, Lars
    KI.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Svensson, Björn
    Helsingborg.
    Antikroppar mot citrullinerade proteiner - genombrott i reumatologisk diagnostik.2004In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 101, no 50, p. 4092-4096Article in journal (Other academic)
  • 49. Samuelsson, A-K
    et al.
    Hydén, Dag
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Oto-Rhiono-Laryngology and Head & Neck Surgery. Östergötlands Läns Landsting, RC - Rekonstruktionscentrum, ÖNH - Öron- Näsa- Halskliniken.
    Roberg, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Infectious Diseases. Östergötlands Läns Landsting, Centre for Medicine, Department of Infectious Diseases in Östergötland.
    Skogh, Thomas
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Molecular and Clinical Medicine, Rheumatology. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Evaluation of anti-hsp70 antibody screening in sudden deafness2003In: Ear and Hearing, ISSN 0196-0202, E-ISSN 1538-4667, Vol. 24, no 3, p. 233-235Article in journal (Refereed)
    Abstract [en]

    Objective: To assess the diagnostic utility of anti-hsp70 antibody screening in sudden deafness. Design: Sera from 27 patients with sudden deafness and 100 healthy blood donors were analyzed by Western blotting (WB) for the presence of antibodies against 68 kD heat shock protein (anti-hsp70). Results: 19% of the patient sera and 14% of the control sera turned out positive, which was not significantly different. Conclusions: The anti-hsp70 WB test lacks clinical utility for diagnostic screening in patients with sudden deafness.

  • 50.
    Simard, Julia F
    et al.
    Karolinska Institute.
    Arkema, Elizabeth V
    Lund University.
    Saxne, Tore
    Lund University.
    Baecklund, Eva
    Uppsala University.
    Cöster, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Rheumatology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
    Dackhammar, Christina
    Sahlgrens University Hospital.
    Jacobsson, Lennart
    Lund University.
    Feltelius, Nils
    Medical Product Agency, Uppsala.
    Lindblad, Staffan
    Karolinska Institute.
    Rantapaa-Dahlqvist, Solbritt
    Umea University, Department Med, Rheumatol Unit, University Hospital, Umea, Sweden .
    Klareskog, Lars
    Karolinska Institute, Karolinska University Hospital, Department Med, Rheumatol Unit, S-17176 Stockholm, Sweden .
    van Vollenhoven, Ronald F
    Karolinska Institute.
    Neovius, Martin
    Karolinska Institute.
    Ten years with biologics: to whom do data on effectiveness and safety apply?2011In: RHEUMATOLOGY, ISSN 1462-0324, Vol. 50, no 1, p. 204-213Article in journal (Refereed)
    Abstract [en]

    Methods. We identified all adult patients with RA (n = 9612), PsA (n = 1417) and other SpA (n = 1652) initiating a first biologic therapy between 1 January 1999 and 31 December 2008, registered in the Swedish Biologics Register (ARTIS), including information on demographics, disease characteristics and 1-year risk of first-line treatment discontinuation. Results. Over calendar time, measures of disease activity at start declined substantially for all indications, and diminished between first-, second- and third-line therapy starts. One-year risks of first-line therapy discontinuation increased. Switchers to anti-TNF and non-TNF biologics had different comorbidities. Despite andlt; 50% drug retention at 5 years, most patients remained exposed to some biologic. Conclusions. The trends in baseline characteristics and drug retention underscores that any effects of biologics, including comparison between different biologics, must be interpreted in light of the characteristics of the population treated. The observed differences further call for continued vigilance to properly evaluate the safety profiles of biologic treatments as they are currently used. Exposure to multiple biologics presents a challenge for attribution of long-term effects.

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