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  • 201.
    D'Elia, Helena Forsblad
    et al.
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Mattsson, Lars-Ake
    Ohlsson, Claes
    Nordborg, Elisabeth
    Carlsten, Hans
    Hormone replacement therapy in rheumatoid arthritis is associated with lower serum levels of soluble IL-6 receptor and higher insulin-like growth factor 1.2003Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 5, nr 4, s. R202-9Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hormone replacement therapy (HRT) modulates the imbalance in bone remodeling, thereby decreasing bone loss. Sex hormones are known to influence rheumatic diseases. The aim of this study was to investigate the effects of HRT on the serum levels of hormones and cytokines regulating bone turnover in 88 postmenopausal women with active rheumatoid arthritis (RA) randomly allocated to receive HRT plus calcium and vitamin D3 or calcium and vitamin D3 alone for 2 years. An increase in estradiol (E2) correlated strongly with improvement of bone mineral density in the hip (P < 0.001) and lumbar spine (P < 0.001). Both baseline levels and changes during the study of IL-6 and erythrocyte sedimentation rate were correlated positively (P < 0.001). HRT for 2 years resulted in an increase of the bone anabolic factor, insulin-like growth factor 1 (IGF-1) (P < 0.05) and a decrease of serum levels of soluble IL-6 receptor (sIL-6R) (P < 0.05), which is known to enhance the biological activity of IL-6, an osteoclast-stimulating and proinflammatory cytokine. Baseline levels of IL-6 and IGF-1 were inversely associated (P < 0.05), and elevation of IGF-1 was connected with decrease in erythrocyte sedimentation rate (P < 0.05) after 2 years. Interestingly, increase in serum levels of E2 was associated with reduction of sIL-6R (P < 0.05) and reduction of sIL-6R was correlated with improved bone mineral density in the lumbar spine (P < 0.05). The latter association was however not significant after adjusting for the effect of E2 (P = 0.075). The influences of IGF-1 and the IL-6/sIL-6R pathways suggest possible mechanisms whereby HRT may exert beneficial effects in RA. However, to confirm this hypothesis future and larger studies are needed.

  • 202. Deminger, A.
    et al.
    Klingberg, E.
    Lorentzon, M.
    Carlsten, H.
    Jacobsson, L. T.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg.
    Changes in volumetric bone mineral density and bone microarchitecture in patients with ankylosing spondylitis. a five-year prospective study using hrpqct2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 916-916Artikel i tidskrift (Övrigt vetenskapligt)
  • 203. Deminger, A.
    et al.
    Klingberg, E.
    Lorentzon, M.
    Carlsten, H.
    Jacobsson, L. T. H.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    FACTORS ASSOCIATED WITH CHANGES IN VOLUMETRIC BONE MINERAL DENSITY IN PATIENTS WITH ANKYLOSING SPONDYLITIS: A FIVE-YEAR PROSPECTIVE STUDY USING HRpQCT2018Ingår i: Clinical and Experimental Rheumatology, ISSN 0392-856X, E-ISSN 1593-098X, Vol. 36, nr 4, s. 706-706Artikel i tidskrift (Övrigt vetenskapligt)
  • 204. Deminger, Anna
    et al.
    Klingberg, Eva
    Geijer, Mats
    Gothlin, Jan
    Hedberg, Martin
    Rehnberg, Eva
    Carlsten, Hans
    Jacobsson, Lennart T.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis2018Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, artikel-id 162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Knowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex. Methods: Swedish patients with AS, age (mean +/- SD) 50 +/- 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples. Results: Of 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 +/- 2.8 vs. 1.2 +/- 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression >= 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women. Conclusion: This first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.

  • 205.
    Deminger, Anna
    et al.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Klingberg, Eva
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Lorentzon, Mattias
    Geriatric Medicine, Institute of Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
    Geijer, Mats
    Örebro universitet, Institutionen för medicinska vetenskaper. Region Örebro län. Department of Radiology, Örebro University Hospital, Örebro, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden.
    Göthlin, Jan
    Department of Radiology, Sahlgrenska University Hospital, Mölndal, Sweden.
    Hedberg, Martin
    Section of Rheumatology, Södra Älvsborg Hospital, Borås, Sweden.
    Rehnberg, Eva
    Section of Rheumatology, Alingsås Hospital, Alingsås, Sweden.
    Carlsten, Hans
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Jacobsson, Lennart T.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Forsblad-d'Elia, Helena
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Public Health and Clinical Medicine, Rheumatology, Umeå University, Umeå, Sweden.
    Which measuring site in ankylosing spondylitis is best to detect bone loss and what predicts the decline: results from a 5-year prospective study2017Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 19, artikel-id 273Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Studies have shown increased prevalence of osteoporosis and increased risk for vertebral fractures in patients with ankylosing spondylitis (AS). Measurements of bone mineral density (BMD) in the lumbar spine anterior-posterior (AP) projection may be difficult to interpret due to the ligamentous calcifications, and the lateral projection might be a better measuring site. Our objectives were to investigate BMD changes after 5 years at different measuring sites in patients with AS and to evaluate disease-related variables and medications as predictors for BMD changes.

    METHODS: In a longitudinal study, BMD in Swedish AS patients, 50 ± 13 years old, was measured with dual-energy x-ray absorptiometry (DXA) at the hip, the lumbar spine AP and lateral projections, and the total radius at baseline and after 5 years. Patients were assessed with questionnaires, blood samples, and spinal radiographs for grading of AS-related alterations in the spine with the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) and assessment of vertebral fractures by the Genant score. Multiple linear regression analyses were used to investigate predictors for BMD changes.

    RESULTS: Of 204 patients included at baseline, 168 (82%) were re-examined after 5 years (92 men and 76 women). BMD decreased significantly at the femoral neck and radius and increased significantly at the lumbar spine, both for AP and lateral projections. Mean C-reactive protein during follow-up predicted a decrease in the femoral neck BMD (change in %, β = -0.15, p = 0.046). Use of bisphosphonates predicted an increase in BMD at all measuring sites (p < 0.001 to 0.013), except for the total radius. Use of tumor necrosis factor inhibitors (TNFi) predicted an increase in AP spinal BMD (β = 3.15, p = 0.012).

    CONCLUSION: The current study (which has a long follow-up, many measuring sites, and is the first to longitudinally assess the lateral projection of the spine in AS patients) surprisingly showed that lateral projection spinal BMD increased. This study suggests that the best site to assess bone loss in AS patients is the femoral neck and that inflammation has an adverse effect, and the use of bisphosphonates and TNFi has a positive effect, on BMD in AS patients.

  • 206.
    Demmelmaier, Ingrid
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Livsstil och rehabilitering vid långvarig sjukdom. Karolinska Inst, Stockholm, Sweden..
    Iversen, Maura D.
    Karolinska Inst, Stockholm, Sweden.;Northeastern Univ, Boston, MA 02115, Sweden.;Harvard Med Sch, Boston, MA, Sweden..
    How Are Behavioral Theories Used in Interventions to Promote Physical Activity in Rheumatoid Arthritis?: A Systematic Review2018Ingår i: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 70, nr 2, s. 185-196Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    ObjectiveTo identify the use of behavioral theories in physical activity interventions in populations with rheumatoid arthritis (RA). MethodsThis review includes articles published in English between January 1, 1980 and November 8, 2015 in MEDLINE, Cochrane, and CINAHL, identified by a strategic literature search. Included studies were published in international peer-reviewed journals, mentioned theory, evaluated a physical activity intervention for adults with RA, and had 1 physical activity variable as the outcome. References and reviews were also checked. Two investigators independently selected articles and extracted data using a validated scale, the theory coding scheme. Additional extracted data included author, sample characteristics, study design, physical activity outcomes, intervention type and duration, and control group. ResultsA total of 245 articles were identified, 211 articles and references were screened, and 29 articles were reviewed. Of these, 18 were excluded, leaving 11 articles with 1,472 participants (75% women). Ten studies (91%) were randomized controlled trials, 8 (73%) assessed physical activity plus self-management, and 3 (27%) physical activity only. Program durations ranged from 5 weeks to 1 year. Eight studies (73%) used a single theory, 7 studies (64%) linked at least 1 intervention technique to theory, 2 studies (18%) analyzed mediating effects of theoretical constructs, and 5 studies (45%) discussed results in relation to theory. ConclusionFindings indicate that physical activity intervention studies claiming the use of behavioral theories use theory to a small extent. We suggest expanding theory use in design, evaluation, and interpretation of physical activity intervention results. Further, we recommend that future studies evaluate the most salient behavioral theories, interventions components, and delivery modes in RA populations.

  • 207.
    Demmelmaier, Ingrid
    et al.
    Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, 23100,Alfred Nobels Alle 23, S-14183 Huddinge, Sweden..
    Åsenlöf, Pernilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Bergman, Patrick
    Linnaeus Univ, Sch Educ Psychol & Sports Sci, Kalmar, Sweden..
    Nordgren, Birgitta
    Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, 23100,Alfred Nobels Alle 23, S-14183 Huddinge, Sweden..
    Opava, Christina H.
    Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, 23100,Alfred Nobels Alle 23, S-14183 Huddinge, Sweden.;Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden..
    Pain rather than self-reported sedentary time explains variation in perceived health and activity limitation in persons with rheumatoid arthritis: a cross sectional study in Sweden2017Ingår i: Rheumatology International, ISSN 0172-8172, E-ISSN 1437-160X, Vol. 37, nr 6, s. 923-930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To investigate (1) the amount of self-reported time spent sedentary among a large cohort of persons with rheumatoid arthritis (RA), and (2) the contribution of sedentary time to explain perceived health and activity limitation in RA beyond that of previously known correlates. This cross-sectional study used data from a postal questionnaire and the Swedish Rheumatology Quality registers (SRQ). The International Physical Activity Questionnaire was used to assess sedentary time (sitting) and moderate, vigorous and walking activity (MVPA). Sociodemographics, pain, fatigue, fear-avoidance beliefs, anxiety/depression, disease duration, MVPA and sedentary time were included in multiple regression models with perceived health (Visual Analogue Scale 0-100) and activity limitation (Stanford Health Assessment Questionnaire) as dependent variables. Results: In all 3152 (59%) of 5391 persons identified as eligible from the SRQ, responded to the questionnaire. 2819 individuals with complete data on all study variables were analysed. Mean time (SD) spent sedentary was 257 (213) minutes per day. Sedentary time did not contribute significantly to explain perceived health and only minimally to explain activity limitation. Instead, variation was mainly explained by pain; for perceived health (Beta = 0.780, p < 0.001) and for activity limitation (Beta = 0.445, p < 0.001).The results indicate a non-significant role of sedentary time and a need for increased focus on pain in the management of RA. Future studies should use prospective designs and objective assessment methods to further investigate the associations between sedentary time and health outcomes in persons with RA.

  • 208.
    Demmelmeier, Ingrid
    et al.
    Karolinska Institutet.
    Åsenlöf, Pernilla
    Uppsala University.
    Bergman, Patrick
    Linnéuniversitetet, Fakulteten för samhällsvetenskap (FSV), Institutionen för idrottsvetenskap (ID).
    Nordgren, Birgitta
    Karolinska Institutet.
    Opava, Christina H
    Karolinska Institutet ; Karolinska University Hospital.
    Pain rather than self-reported sedentary time explains variation in perceived health and activity limitation in persons with rheumatoid arthritis: a cross sectional study in Sweden2017Ingår i: Rheumatology International, ISSN 0172-8172, E-ISSN 1437-160X, Vol. 37, nr 6, s. 923-930Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    To investigate (1) the amount of self-reported time spent sedentary among a large cohort of persons with rheumatoid arthritis (RA), and (2) the contribution of sedentary time to explain perceived health and activity limitation in RA beyond that of previously known correlates. This cross-sectional study used data from a postal questionnaire and the Swedish Rheumatology Quality registers (SRQ). The International Physical Activity Questionnaire was used to assess sedentary time (sitting) and moderate, vigorous and walking activity (MVPA). Sociodemographics, pain, fatigue, fear-avoidance beliefs, anxiety/depression, disease duration, MVPA and sedentary time were included in multiple regression models with perceived health (Visual Analogue Scale 0-100) and activity limitation (Stanford Health Assessment Questionnaire) as dependent variables.

    RESULTS:

    In all 3152 (59%) of 5391 persons identified as eligible from the SRQ, responded to the questionnaire. 2819 individuals with complete data on all study variables were analysed. Mean time (SD) spent sedentary was 257 (213) minutes per day. Sedentary time did not contribute significantly to explain perceived health and only minimally to explain activity limitation. Instead, variation was mainly explained by pain; for perceived health (Beta = 0.780, p < 0.001) and for activity limitation (Beta = 0.445, p < 0.001).The results indicate a non-significant role of sedentary time and a need for increased focus on pain in the management of RA. Future studies should use prospective designs and objective assessment methods to further investigate the associations between sedentary time and health outcomes in persons with R

  • 209. Denoncourt, R. N.
    et al.
    Adams, D.
    Gonzalez-Duarte, A.
    O'Riordan, W.
    Yang, C.
    Yamashita, T.
    Kristen, A.
    Tournev, I
    Schmidt, H.
    Coelho, T.
    Berk, J.
    Lin, K.
    Chen, J.
    Gollob, J.
    Suhr, Ole
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burden of Illness for Patients with Hereditary Attr Amyloidosis with Polyneuropathy Begins with Symptom Onset and Increases with Disease Progression2016Konferensbidrag (Refereegranskat)
  • 210. Di Giuseppe, D.
    et al.
    Frisell, T.
    Ernestam, S.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lindqvist, E.
    Lindstrom, U.
    Sjowall, C.
    Askling, J.
    Assessment of biosimilars using real world data: the complexity of choosing a comparator and understanding uptake2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 452-453Artikel i tidskrift (Övrigt vetenskapligt)
  • 211. Di Giuseppe, Daniela
    et al.
    Frisell, Thomas
    Ernestam, Sofia
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lindqvist, Elisabet
    Lindström, Ulf
    Sjöwall, Christopher
    Askling, Johan
    Uptake of rheumatology biosimilars in the absence of forced switching2018Ingår i: Expert Opinion on Biological Therapy, ISSN 1471-2598, E-ISSN 1744-7682, Vol. 18, nr 5, s. 499-504Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To describe the uptake and system-level effects of the introduction of biosimilars in a setting without forced switching.Research design and methods: We used data from the Swedish Rheumatology Quality register from start of marketing of infliximab (Remsima (R) and Inflectra (R)) and etanercept (Benepali (R)) biosimilars until 31 December 2016. We compared users of each originator-product and its biosimilar(s) by line of treatment: bDMARD-naive patients, non-medical switchers (vs. matched patients remaining on originator), and patients switching from a previous bDMARD of another type.Results: From the start of marketing 1343 patients started an infliximab biosimilar (22 months) and 2691 started etanercept (9months). Overall, the introduction of these biosimilars resulted in an increase of the total number of ongoing infliximab and etanercept treatments (originator + biosimilar) . At the end of the study period, biosimilars accounted for 31% of all infliximab treatments and 31% of all etanercept-treated patients. For each line of therapy, we noted only small differences in patient characteristics between those starting the originator product vs. its biosimilar(s).Conclusions: Introduction of biosimilars have effects beyond replacement of the originator product, in terms of an increased rate of bDMARD initiation. Selection to non-medical switching displayed no particular disease- or patient-characteristics.

  • 212. Di Giuseppe, Daniela
    et al.
    Ljung, Lotta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundström, Björn
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Meat Consumption and Risk of Rheumatoid Arthritis in Women: A Population-Based Cohort Study2018Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 70, nr S9, artikel-id 203Artikel i tidskrift (Övrigt vetenskapligt)
    Abstract [en]

    Background/Purpose: Mixed results have been reported for the association between meat consumption and the risk of developing rheumatoid arthritis (RA). The aim of this study was to evaluate the association between red meat, particularly processed meat, and the risk of RA using data from a population-based cohort of women.

    Methods: We prospectively followed 35,600 women aged 48-83 years from the Swedish Mammography Cohort (SMC), between 2003 and 2014. Meat consumption was assessed with a 96-item self-administered questionnaire in 1997. A corresponding questionnaire data from 1987 was available, enabling identification of long-term meat consumption. The relative risk (RR) of RA associated with meat consumption and its 95% confidence interval (CI) were estimated using Cox proportional hazard regression models. Multivariable models were adjusted for age, body mass index, educational level, physical activity, use of dietary supplements, energy intake, and smoking.

    Results: During the 12 years of follow-up (381 456 person years), 368 new cases of rheumatoid arthritis were identified. Meat consumption was not associated with the development of RA in age-adjusted (RR=0.96 (95% CI: 0.69-1.32)) or multivariable adjusted (RR=1.08 (95%CI: 0.77-1.53)) models (Table 1). No association was observed either for consumption of type-specific meat, such as red meat (RR=1.08 (95% CI: 0.77-1.50)), processed meat (RR=0.84 (95% CI: 0.59-1.22)), or poultry (RR=0.88 (95% CI: 0.60-1.31)). , Women with a consistent long-term consumption of meat of >7 servings/week over a period of 10 years had no increased risk of RA, HR 1.19 (95% CI: 0.78-1.80), compared to women with a consistent consumption of <=4 servings/week.

    Conclusion: In this large population-based cohort study, meat consumption, in total, by sub-types, or over time, was not associated with the risk of RA development in women.

  • 213.
    Dickens, Alex Mountfort
    et al.
    Turku Centre for Biotechnology, University of Turku, Turku, Finland .
    Posti, Jussi P.
    Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland .
    Takala, Riikka Sk.
    Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland .
    Ala-Seppälä, Henna Maria
    Department of Neurology,University of Turku, Turku, Finland .
    Mattila, Ismo
    Steno Diabetes Center AS, Gentofte, Denmark.
    Coles, Jonathan Coles
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Frantzén, Janek
    Division of Clinical Neurosciences, Department of Rehabilitation and Brain Trauma, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland; Division of Clinical Neurosciences, Department of Neurosurgery,Turku University Hospital, Turku, Finland .
    Hutchinson, Peter John
    Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Katila, Ari J.
    Perioperative Services, Intensive Care Medicine and Pain Management, Turku University Hospital, Turku, Finland.
    Kyllönen, Anna
    Department of Neurology, University of Turku, Turku, Finland .
    Maanpää, Henna-Riikka
    Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.
    Newcombe, Virginia
    Division of Anaesthesia, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom of Great Britain and Norther Ireland.
    Outtrim, Joanne
    Division of Anaesthesia, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Tallus, Jussi
    Division of Anaesthesia, Addenbrooke's Hospital, Hills Road, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Carpenter, Keri
    Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Menon, David
    Head, Division of Anaesthesia, Addenbrooke's Hospital, Cambridge, United Kingdom of Great Britain and Northern Ireland .
    Hyötyläinen, Tuulia
    Örebro universitet, Institutionen för naturvetenskap och teknik.
    Tenovuo, Olli
    Division of Clinical Neurosciences, Department of Neurosurgery, Turku University Hospital, Turku, Finland; Department of Neurology, University of Turku, Turku, Finland .
    Oresic, Matej
    Örebro universitet, Institutionen för medicinska vetenskaper. Turku Centre for Biotechnology, University of Turku, Turku, Finland.
    Serum metabolites associate with CT findings following TBI2018Ingår i: Journal of Neurotrauma, ISSN 0897-7151, E-ISSN 1557-9042Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    There is a need to rapidly detect patients with traumatic brain injury (TBI) who require head computed tomography (CT). Given the energy crisis in the brain following TBI, we hypothesized that serum metabolomics would be a useful tool for developing a set of biomarkers to determine the need for CT and to distinguish between different types of injuries observed. Logistic regression models using metabolite data from the discovery cohort (n=144, Turku, Finland) were used to distinguish between patients with traumatic intracranial findings and negative findings on head CT. The resultant models were then tested in the validation cohort (n=66, Cambridge, UK). The levels of glial fibrillary acidic protein and ubiquitin C-terminal hydrolase-L1 were also quantified in the serum from the same patients. Despite there being significant differences in the protein biomarkers in patients with TBI, the model that determined the need for a CT scan validated poorly (AUC=0.64: Cambridge patients). However, using a combination of six metabolites (two amino acids, three sugar derivatives and one ketoacid) it was possible to discriminate patients with intracranial abnormalities on CT and patients with a normal CT (AUC=0.77 in Turku patients and AUC=0.73 in Cambridge patients). Furthermore, a combination of three metabolites could distinguish between diffuse brain injuries and mass lesions (AUC=0.87 in Turku patients and AUC=0.68 in Cambridge patients). This study identifies a set of validated serum polar metabolites, which associate with the need for a CT scan. Additionally, serum metabolites can also predict the nature of the brain injury. These metabolite markers may prevent unnecessary CT scans, thus reducing the cost of diagnostics and radiation load.

  • 214.
    Dieker, Jurgen
    et al.
    Radboud University of Nijmegen, Netherlands.
    Berden, Jo H.
    Radboud University of Nijmegen, Netherlands.
    Bakker, Marinka
    Radboud University of Nijmegen, Netherlands.
    Briand, Jean-Paul
    CNRS, France.
    Muller, Sylviane
    CNRS, France.
    Voll, Reinhard
    University of Medical Centre Freiburg, Germany; University of Medical Centre Freiburg, Germany.
    Sjöwall, Christopher
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Herrmann, Martin
    Friedrich Alexander University of Erlangen Nuremberg, Germany.
    Hilbrands, Luuk B.
    Radboud University of Nijmegen, Netherlands.
    van der Vlag, Johan
    Radboud University of Nijmegen, Netherlands.
    Autoantibodies against Modified Histone Peptides in SLE Patients Are Associated with Disease Activity and Lupus Nephritis2016Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, nr 10, artikel-id e0165373Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Persistent exposure of the immune system to death cell debris leads to autoantibodies against chromatin in patients with systemic lupus erythematosus (SLE). Deposition of antichromatin/ chromatin complexes can instigate inflammation in multiple organs including the kidney. Previously we identified specific cell death-associated histone modifications as targets of autoantibodies in SLE. In this study we addressed, in a large cohort of SLE patients and controls, the question whether plasma reactivities with specific histone peptides associated with serology and clinical features. Plasma from SLE patients with and without lupus nephritis, disease controls, and healthy controls, were tested in ELISA with histone H4 peptide acetylated at lysines 8, 12 and 16 (H4p(ac)), H2B peptide acetylated at lysine 12 (H2Bp(ac)), H3 peptide trimethylated at lysine 27 (H3p(me)), and their unmodified equivalents. SLE patients displayed a higher reactivity with the modified equivalent of each peptide. Reactivity with H4p(ac) showed both a high sensitivity (89%) and specificity (91%) for SLE, while H2Bp(ac) exhibited a high specificity (96%) but lower sensitivity (69%). Reactivity with H3p(me) appeared not specific for SLE. Anti-H4p(ac) and anti-H2Bp(ac) reactivity demonstrated a high correlation with disease activity. Moreover, patients reacting with multiple modified histone peptides exhibited higher SLEDAI and lower C3 levels. SLE patients with renal involvement showed higher reactivity with H2B/H2Bp(ac) and a more pronounced reactivity with the modified equivalent of H3p(me) and H2Bp(ac). In conclusion, reactivity with H4p(ac) and H2Bp(ac) is specific for SLE patients and correlates with disease activity, whereas reactivity with H2Bp(ac) is in particular associated with lupus nephritis.

  • 215.
    Dobrydnjov, Igor
    et al.
    Department of Rheumasurgery, Spenshult Hospital, Oskarström, Sweden.
    Anderberg, Christian
    Department of Rheumasurgery, Spenshult Hospital, Oskarström, Sweden.
    Olsson, Christer
    Department of Rheumasurgery, Spenshult Hospital, Oskarström, Sweden.
    Shapurova, Olga
    Department of Rheumasurgery, Spenshult Hospital, Oskarström, Sweden.
    Angel, Krister
    Department of Rheumasurgery, Spenshult Hospital, Oskarström, Sweden.
    Bergman, Stefan
    Spenshult Hospital, Oskarström, Sweden.
    Intraarticular vs. extraarticular ropivacaine infusion following high-dose local infiltration analgesia after total knee arthroplasty: a randomized double-blind study2011Ingår i: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 82, nr 6, s. 692-698Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND AND PURPOSE: Ropivacaine infusion following high-volume local infiltration analgesia has been shown to be effective after total knee arthroplasty, but the optimum site of administration of ropivacaine has not been evaluated. We compared the effects of intraarticular and extraarticular adminstration of the local anesthetic for postoperative supplementation of high-volume local infiltration analgesia.

    PATIENTS AND METHODS: In this double-blind study, 36 rheumatic patients aged 51-78 years with physical status ASA 2-3 who were scheduled for total knee arthroplasty were randomized into 2 groups. All patients received wound infiltration at the end of surgery with 300 mg ropivacaine, 30 mg ketorolac, and 0.5 mg epinephrine (total volume 156 mL). A tunneled catheter was randomly placed either extraarticularly or intraarticularly. Continuous infusion of ropivacain (0.5%, 2 mL/h) was started immediately and was maintained during the next 48 h. Pain intensity at rest, on movement, and with mobilization was estimated by the patients and the physiotherapist; rescue morphine consumption was recorded.

    RESULTS: As estimated by the patients, ropivacaine administered intraarticularly did not improve analgesia relative to extraarticular infusion, but improved the first mobilization. The incidence of high intensity of pain (VAS 7-10) was less in the group with intraarticular infusion. Analgesic requirements were similar in the 2 groups (47 mg and 49 mg morphine). No complications of postoperative wound healing were seen and there were no toxic side effects.

    INTERPRETATION: Continuous infusion of ropivacaine intraarticulary did not improve postoperative analgesia at rest relative to extraarticular administration, but it appeared to reduce the incidence of high pain intensity during first exercises, and could therefore be expected to improve mobilization up to 24 h after total knee arthroplasty.

  • 216. Dyke, Stephanie O M
    et al.
    Cheung, Warren A
    Joly, Yann
    Ammerpohl, Ole
    Lutsik, Pavlo
    Rothstein, Mark A
    Caron, Maxime
    Busche, Stephan
    Bourque, Guillaume
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Flicek, Paul
    Beck, Stephan
    Hirst, Martin
    Stunnenberg, Henk
    Siebert, Reiner
    Walter, Jörn
    Pastinen, Tomi
    Epigenome data release: a participant-centered approach to privacy protection2015Ingår i: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 16, artikel-id 142Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Large-scale epigenome mapping by the NIH Roadmap Epigenomics Project, the ENCODE Consortium and the International Human Epigenome Consortium (IHEC) produces genome-wide DNA methylation data at one base-pair resolution. We examine how such data can be made open-access while balancing appropriate interpretation and genomic privacy. We propose guidelines for data release that both reduce ambiguity in the interpretation of open-access data and limit immediate access to genetic variation data that are made available through controlled access.

  • 217.
    Edvinsson, Marie
    et al.
    Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
    Welvaart, Nicole
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Orthopaedics.
    Ryttberg, Lars
    Department of Orthopaedics, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Wretenberg, Per
    Örebro universitet, Institutionen för medicinska vetenskaper. Department of Orthopaedics.
    Vikerfors, Tomas
    Department of Infectious Diseases, Örebro University, Örebro, Sweden; Västerås Central Hospital, Västerås, Sweden.
    Nyström-Rosander, Christina
    Department of Medical Sciences, Infectious Diseases, Uppsala University, Uppsala, Sweden.
    No evidence of Chlamydia pneumoniae in the synovia of patients with osteoarthritis2018Ingår i: Journal of international medical research, ISSN 0300-0605, E-ISSN 1473-2300Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Osteoarthritis (OA) is a common cause of disability affecting millions of people of all ages worldwide. The pathogenesis involves an inflammatory component, but the cause of the inflammation remains incompletely understood. The intracellular bacteria Chlamydia trachomatis and C. pneumoniae have been demonstrated in patients with reactive arthritis. Both of these microorganisms can cause chronic and persistent infections, with C. trachomatis being the most common cause of reactive arthritis. This study was performed to investigate the presence of C. pneumoniae in a large number of patients with primary OA.

    METHODS: The study included 75 patients who underwent total knee arthroplasty. During surgery, a synovial biopsy was performed and synovial fluid drawn. Real-time polymerase chain reaction (PCR) of C. pneumoniae was run on all patients, and real-time PCR of bacterial 16S rDNA was conducted on 30 of the 75 patients to screen for the presence of other bacteria.

    RESULTS: Real-time PCR showed no evidence of the presence of C. pneumoniae in the patients' specimens, nor were other bacteria detected.

    CONCLUSIONS: Although an inflammatory component is part of the pathogenesis of OA, we found no evidence indicating that C. pneumoniae is a stimulator of that inflammation.

  • 218.
    Ekelund, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Ryhov Cty Hosp, Dept Pediat, Jonkoping, Sweden..
    Aalto, Kristiina
    Univ Helsinki Hosp, Childrens Hosp, Dept Pediat, Helsinki, Finland..
    Fasth, Anders
    Gothenburg Univ, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden..
    Herlin, Troels
    Arhus Univ Hosp, Dept Pediat, Aarhus, Denmark..
    Nielsen, Susan
    Rigshosp, Copenhagen Univ Hosp, Pediat Rheumatol Dept, Pediat Clin 2, Copenhagen, Denmark..
    Nordal, Ellen
    Univ Hosp North Norway, Dept Pediat, Tromso, Norway.;UIT Arctic Univ Norway, Dept Clin Med, Tromso, Norway..
    Peltoniemi, Suvi
    Univ Helsinki Hosp, Childrens Hosp, Dept Pediat, Helsinki, Finland..
    Rygg, Marite
    Norwegian Univ Sci & Technol, Dept Lab Med Childrens & Womens Hlth, Trondheim, Norway.;St Olavs Hosp, Dept Pediat, Trondheim, Norway..
    Zak, Marek
    Pediatric Rheumatology Department, Pediatric Clinic II, Copenhagen University Hospital.
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa.
    Psoriasis and associated variables in classification and outcome of juvenile idiopathic arthritis - an eight-year follow-up study2017Ingår i: Pediatric Rheumatology, ISSN 1546-0096, E-ISSN 1546-0096, Vol. 15, artikel-id 13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To study the impact of psoriasis and features associated with psoriasis on classification and outcome in a population-based follow-up cohort of children with juvenile idiopathic arthritis (JIA). Methods: In all, 440 children with JIA were followed for a median of 8 years in a prospective Nordic population-based cohort study. Data for remission was available for 427 of these children. The presence of psoriasis, psoriasis-like rash, dactylitis, nail pitting, enthesitis, tenosynovitis and heredity was assessed in relation to ILAR classification and remission. Results: Clinical findings associated with psoriasis developed consecutively during the 8-year period. Six of 14 children with psoriasis were not classified as juvenile psoriatic arthritis according to the ILAR criteria at 8 year follow-up. Dactylitis was more common in children with early onset of JIA. After 8 years we found a cumulative median number of eleven arthritic joints in children with psoriasis or psoriasis- like rash compared with six in the rest of the cohort (p = 0.02). Also, the chance for not being in remission after 8 years increased significantly in patients with psoriasis, psoriasis-like rash or at least two of: 1) first-degree heredity for psoriasis or psoriatic arthritis, 2) dactylitis or 3) nail pitting, compared with the rest of the group (OR 3.32, p = 0.010). Conclusions: Our results indicate a more severe disease over time in psoriasis- associated JIA, as features of psoriasis develop during the disease course. This group is a major challenge to encompass in a future JIA classification in order to facilitate early tailored treatment.

  • 219.
    Ekelund, Maria
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa. Ryhov Cty Hosp, Dept Pediat, Jönköping, Sweden. .
    Berntson, Lillemor
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kvinnors och barns hälsa, Forskargrupper (Inst. för kvinnor och barns hälsa), Pediatrisk inflammationsforskning.
    Consolaro, Alessandro
    Ist Giannina Gaslini, Paediat Rheumatol Int Trials Org PRINTO, Clin Pediat & Reumatol, Via Gaslini 5, I-16147 Genoa, Italy;Univ Genoa, Dipartimento Pediat, Genoa, Italy.
    Bovis, Francesca
    Ist Giannina Gaslini, Paediat Rheumatol Int Trials Org PRINTO, Clin Pediat & Reumatol, Via Gaslini 5, I-16147 Genoa, Italy.
    Ruperto, Nicolino
    Ist Giannina Gaslini, Paediat Rheumatol Int Trials Org PRINTO, Clin Pediat & Reumatol, Via Gaslini 5, I-16147 Genoa, Italy.
    The Swedish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR)2018Ingår i: Rheumatology International, ISSN 0172-8172, E-ISSN 1437-160X, Vol. 38, nr Suppl. 1, s. 371-377Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient-reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Swedish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability and construct validity (convergent and discriminant validity). A total of 68 JIA patients (8.8% systemic, 44.1% oligoarticular, 13.2% RF negative polyarthritis, 33.9% other categories) and 76 healthy children, were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Swedish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

  • 220.
    Eklund, Andreas
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bergström, Gunnar
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Axén, Iben
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Research Department, Spine Center of Southern Denmark, Hospital Lillebaelt, Institute of Regional Health Research, Middelfart, Denmark.
    Do psychological and behavioral factors classified by the West Haven-Yale Multidimensional Pain Inventory (Swedish version) predict the early clinical course of low back pain in patients receiving chiropractic care?2016Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, nr 1, artikel-id 75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: To investigate if psychological and behavioral factors (as determined by the Swedish version of the West Haven-Yale Multidimensional Pain Inventory, MPI-S) can predict the early clinical course of Low Back Pain (LBP).

    Methods: MPI-S data from patients (18–65 years of age) seeking chiropractic care for recurrent and persistent LBP were collected at the 1st visit. A follow-up questionnaire was administered at the 4th visit. The predictive value of the MPI-S subgroups Adaptive Copers (AC), Interpersonally Distressed (ID) and Dysfunctional (DYS) was calculated against the subjective improvement at the 4th visit and clinically relevant difference in pain intensity between the 1st and 4th visit.

    Results: Of the 666 subjects who were included at the 1st visit, 329 completed the questionnaire at the 4th visit. A total of 64.7 % (AC), 68.0 % (ID) and 71.3 % (DYS) reported a definite improvement. The chance of “definite improvement”, expressed as relative risk (95 % CI) with the AC group as reference, was 1.05 (.87–1.27) for the ID and 1.10 (.93–1.31) for the DYS groups, respectively. The DYS and ID groups reported higher values in pain intensity both at the 1st and the 4th visit. The proportion of subjects who reported an improvement in pain intensity of 30 % or more (clinically relevant) were 63.5 % AC, 72.0 % ID and 63.2 % DYS. Expressed as relative risk (95 % CI) with the AC group as reference, this corresponded to 1.26 (.91–1.76) for the ID and 1.09 (.78–1.51) for the DYS groups, respectively.

    Conclusions: The MPI-S instrument could not predict the early clinical course of recurrent and persistent LBP in this sample of chiropractic patients.

  • 221.
    Eklund, Andreas
    et al.
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden.
    Bergström, Gunnar
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden.
    Bodin, Lennart
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden.
    Axén, Iben
    Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institutet, Stockholm, Sweden; Research Department, Spine Center of Southern Denmark, Institute of Regional Health Research, Hospital Lillebælt, Middelfart, Denmark.
    Psychological and behavioral differences between low back pain populations: a comparative analysis of chiropractic, primary and secondary care patients2015Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, artikel-id 306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Psychological, behavioral and social factors have long been considered important in the development of persistent pain. Little is known about how chiropractic low back pain (LBP) patients compare to other LBP patients in terms of psychological/behavioral characteristics.

    Methods: In this cross-sectional study, the aim was to investigate patients with LBP as regards to psychosocial/behavioral characteristics by describing a chiropractic primary care population and comparing this sample to three other populations using the MPI-S instrument. Thus, four different samples were compared. A: Four hundred eighty subjects from chiropractic primary care clinics. B: One hundred twenty-eight subjects from a gainfully employed population (sick listed with high risk of developing chronicity). C: Two hundred seventy-three subjects from a secondary care rehabilitation clinic. D: Two hundred thirty-five subjects from secondary care clinics. The Swedish version of the Multidimensional Pain Inventory (MPI-S) was used to collect data. Subjects were classified using a cluster analytic strategy into three pre-defined subgroups (named adaptive copers, dysfunctional and interpersonally distressed).

    Results: The data show statistically significant overall differences across samples for the subgroups based on psychological and behavioral characteristics. The cluster classifications placed (in terms of the proportions of the adaptive copers and dysfunctional subgroups) sample A between B and the two secondary care samples C and D.

    Conclusions: The chiropractic primary care sample was more affected by pain and worse off with regards to psychological and behavioral characteristics compared to the other primary care sample. Based on our findings from the MPI-S instrument the 4 samples may be considered statistically and clinically different.

  • 222. Elefteria, Dhima
    et al.
    Ejdervik Lindblad, Birgitta
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Central serous chorioretinopathy as a first sign of severe undiagnosed SLE in a pregnant woman2017Konferensbidrag (Refereegranskat)
  • 223.
    Eloranta, Maija-Leena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Alm, Gunnar V
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Disease Mechanisms in RheumatologyTools and Pathways: Plasmacytoid Dendritic Cells and Their Role in AutoimmuneRheumatic Diseases2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 4, s. 853-863Artikel i tidskrift (Refereegranskat)
  • 224.
    Eloranta, Maija-Leena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Franck-Larsson, Karin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Lövgren, Tanja
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Kalamajski, Sebastian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Rönnblom, Anders
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rubin, Kristofer
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Alm, Gunnar V.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Type I interferon system activation and association with disease manifestations in systemic sclerosis2010Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 69, nr 7, s. 1396-1402Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To study the presence of interferogenic autoantibodies in systemic sclerosis (SSc) and their correlation with clinical manifestations, serum levels of interferon alpha (IFNalpha) and chemokines of importance in the disease process. METHODS: Peripheral blood mononuclear cells (PBMCs) or purified plasmacytoid dendritic cells (pDCs) from healthy donors were stimulated with sera from patients with SSc (n=70) or healthy individuals (n=30), together with necrotic or apoptotic cell material. The IFNalpha produced and serum levels of IFNalpha, IFN-inducible protein-10 (IP-10)/chemokine (C-X-C motif) ligand 10, monocyte chemoattractant protein-1 (MCP-1)/(C-C motif) ligand-2 (CCL-2), macrophage inflammatory protein-1alpha (MIP-1alpha)/CCL-3 and RANTES/CCL-5 were measured and correlated with the presence of autoantibodies and clinical manifestations in the patients with SSc. RESULTS: Sera from both diffuse SSc and limited SSc contained interferogenic antibodies, which correlated with the presence of anti-ribonucleoprotein and anti-Sjögren syndrome antigen autoantibodies. The pDCs were responsible for the IFNalpha production which required interaction with FcgammaRII and endocytosis. Increased serum levels of IP-10 were associated with vascular manifestations such as cardiac involvement (p=0.027) and pulmonary arterial hypertension (p=0.036). Increased MCP-1 or IFNalpha serum levels were associated with lung fibrosis (p=0.019 and 0.048, respectively). Digital ulcers including digital loss were associated with increased serum levels of IFNalpha (p=0.029). CONCLUSION: An activated type I IFN system previously seen in several other systemic autoimmune diseases is also present in SSc and may contribute to the vascular pathology and affect the profibrotic process.

  • 225.
    Eloranta, Maija-Leena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Cause and consequences of the activated type I interferon system in SLE2016Ingår i: Journal of Molecular Medicine, ISSN 0946-2716, E-ISSN 1432-1440, Vol. 94, nr 10, s. 1103-1110Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with systemic lupus erythematosus (SLE) have an increased expression of type I interferon (IFN)-regulated genes (an IFN signature), which is caused by an ongoing production of type I IFNs by plasmacytoid dendritic cells (pDCs). The reasons behind the continuous IFN production in SLE are the presence of self-derived IFN inducers and a lack of negative feed-back signals that downregulate the IFN response. In addition, several cells in the immune system promote the IFN production by pDCs and gene variants in the type I IFN signaling pathway contribute to the IFN signature. The type I IFNs act as an immune adjuvant and stimulate T cells, B cells, and monocytes, which all play an important role in the loss of tolerance and persistent autoimmune reaction in SLE. Consequently, new treatments aiming to inhibit the activated type I IFN system in SLE are now being developed and investigated in clinical trials.

  • 226.
    Eloranta, Maija-Leena
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Dual role of CpG-stimulated B cells in the regulation of dendritic cells: comment on the article by Berggren et al Reply2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 8, s. 2216-Artikel i tidskrift (Övrigt vetenskapligt)
  • 227.
    Elshafie, Amir
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Elkhalifa, Abdalla D.
    Weitoft, Thomas
    Nur, Musa
    Elagib, Elnour
    Aledrissy, Mawahib
    Elbagir, Sahwa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Disease Severity and Treatment of Rheumatoid Arthritis: A Comparative Study Between Sudan and Sweden2014Ingår i: ARTHRITIS & RHEUMATOLOGY, ISSN 2326-5191, Vol. 66, nr S10, s. S676-S676, artikel-id 1534Artikel i tidskrift (Övrigt vetenskapligt)
  • 228.
    ElShafie, Amir Ibrahim
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Elkhalifa, Abdalla D.
    Gavle Cent Hosp, Rheumatol Unit, Gavle, Sweden..
    Elbagir, Sahwa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi. Khartoum Fertil Ctr, Khartoum, Sudan..
    Aledrissy, Mawahib I. E.
    Alribat Univ Hosp, Rheumatol Unit, Khartoum, Sudan..
    Elagib, Elnour M.
    Mil Hosp, Rheumatol Unit, Omdurman, Sudan..
    Nur, Musa A. M.
    Alribat Univ Hosp, Rheumatol Unit, Khartoum, Sudan..
    Weitoft, Tomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning, Gävleborg. Gavle Cent Hosp, Rheumatol Unit, Gavle, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Active Rheumatoid Arthritis in Central Africa: A Comparative Study Between Sudan and Sweden2016Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 43, nr 10, s. 1777-1786Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To compare clinical characteristics and treatment between simultaneously investigated Sudanese and Swedish outpatients with rheumatoid arthritis (RA).

    Methods. Outpatients with RA from Sudan (n = 281) and Sweden (n = 542) diagnosed according to the 1987 American College of Rheumatology criteria were recruited between December 2008 and September 2010 and compared concerning clinical presentation, treatment, and laboratory findings, including immunoglobulin M with rheumatoid factor (IgM-RF).

    Results. Sudanese patients had lower inclusion age (median 49 vs 68 yrs), disease duration (48 vs 107 mos), and disease onset age (43 vs 56 yrs) as compared with Swedish patients (p < 0.0001 for all). When stratified concerning the age of inclusion, Swedish patients between 41-50 years had, however, a significantly lower age of onset, with a similar trend for all age groups above 30 years. The female preponderance was higher among Sudanese patients (89.3% vs 72.5%, p < 0.0001), and smoking was nonexistent among Sudanese female patients (p < 0.0001). Erythrocyte sedimentation rate levels and number of tender joints were significantly higher among Sudanese patients. The proportion of IgM-RF positivity was lower among Sudanese patients with RA (52.4% vs 75.5%, p < 0.0001). Higher proportions of Sudanese patients with RA were treated with methotrexate (MTX) and disease-modifying antirheumatic drug combinations, but none of them used biologics. Sudanese patients used lower doses of MTX and sulfasalazine (p < 0.0001) and higher doses of prednisolone (p < 0.0001) than Swedish patients.

    Conclusion. Sudanese patients with RA have significantly higher disease activity and are often IgM-RF-seronegative. Together with reports from Uganda and Cameroon, our data indicate a cluster of highly active and often seronegative RA in central Africa.

  • 229.
    Emilson, Christina
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Åsenlöf, Pernilla
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Pettersson, S.
    Karolinska Inst, Div Physiotherapy, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.;Karolinska Univ Hosp, Dept Rheumatol, Stockholm, Sweden..
    Bergman, S.
    Res & Dev Ctr Spenshult, Halmstad, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Publ Hlth & Community Med, Gothenburg, Sweden..
    Sandborgh, M.
    Malardalen Univ, Sch Hlth Care & Social Welf, Vasteras, Sweden..
    Martin, Cathrin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Demmelmaier, Ingrid
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för neurovetenskap, Fysioterapi.
    Physical therapists' assessments, analyses and use of behavior change techniques in initial consultations on musculoskeletal pain: direct observations in primary health care2016Ingår i: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 17, artikel-id 316Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Behavioral medicine (BM) treatment is recommended to be implemented for pain management in physical therapy. Its implementation requires physical therapists (PTs), who are skilled at performing functional behavioral analyses based on physical, psychological and behavioral assessments. The purpose of the current study was to explore and describe PTs' assessments, analyses and their use of behavioral change techniques (BCTs) in initial consultations with patients who seek primary health care due to musculoskeletal pain. Methods: A descriptive and explorative research design was applied, using data from video recordings of 12 primary health care PTs. A deductive analysis was performed, based on a specific protocol with definitions of PTs' assessment of physical and psychological prognostic factors (red and yellow flags, respectively), analysis of the clinical problem, and use of BCTs. An additional inductive analysis was performed to identify and describe the variation in the PTs' clinical practice. Results: Red and yellow flags were assessed in a majority of the cases. Analyses were mainly based on biomedical assessments and none of the PTs performed functional behavioral analyses. All of the PTs used BCTs, mainly instruction and information, to facilitate physical activity and improved posture. The four most clinically relevant cases were selected to illustrate the variation in the PTs' clinical practice. The results are based on 12 experienced primary health care PTs in Sweden, limiting the generalizability to similar populations and settings. Conclusion: Red and yellow flags were assessed by PTs in the current study, but their interpretation and integration of the findings in analyses and treatment were incomplete, indicating a need of further strategies to implement behavioral medicine in Swedish primary health care physical therapy.

  • 230.
    Eneslätt, Kjell
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Uddhammar, Agneta
    Sundqvist, Karl-Gösta
    The regulation of FasL expression: a distinguishing feature between monocytes and T lymphocytes/NK cells with possible implications for SLE2001Ingår i: Journal of Clinical Immunology, ISSN 0271-9142, E-ISSN 1573-2592, Vol. 21, nr 3, s. 183-192Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Monocytes and lymphocytes from patients with systemic lupus erythematosus (SLE) had a higher cell surface expression of Fast than the corresponding cells from healthy individuals. Inhibitors of metalloproteases upregulated the surface expression of Fast in peripheral blood lymphocytes (PBL), indicating that a metalloprotease is responsible for the cleavage of FasL. The level of sFasL in serum was slightly increased in the patient group compared to the controls. Therefore, the possible contribution of various mononuclear cell types to the release of Fast was analyzed. Isolated NK cells and T lymphocytes released Fast into the medium and the release was prevented by inhibitors of metalloproteases. In contrast, isolated monocytes did not release Fast. FasR expression was elevated in patients with inverted CD4/CD8 ratio, while Fast expression showed no relationship to CD4/CD8 ratio. The absence of Fast release by isolated cells and a high level of surface expression of Fast distinguish monocytes and T lymphocytes/NK cells.

  • 231. Engdahl, C.
    et al.
    Raufer, J.
    Harre, U.
    Bondt, A.
    Pfeifle, R.
    Kroenke, G.
    Scherer, H. U.
    Forsblad, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Department of Rhemtology and Inflammation reserch, CBAR, Institue of Medicine, Gothenburg, Sweden.
    Schett, G.
    Estrogen influences the sialylation profile and inflammatory properties of antibodies – a potential explanation for the sex differences and increased risk for ra in postmenopausal women2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 775-775Artikel i tidskrift (Övrigt vetenskapligt)
  • 232. Engdahl, Cecilia
    et al.
    Bondt, Albert
    Harre, Ulrike
    Raufer, Jasmin
    Pfeifle, René
    Camponeschi, Alessandro
    Wuhrer, Manfred
    Seeling, Michaela
    Mårtensson, Inga-Lill
    Nimmerjahn, Falk
    Krönke, Gerhard
    Scherer, Hans U.
    Forsblad-d'Elia, Helena
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Schett, Georg
    Estrogen induces St6gal1 expression and increases IgG sialylation in mice and patients with rheumatoid arthritis: a potential explanation for the increased risk of rheumatoid arthritis in postmenopausal women2018Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 20, artikel-id 84Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Rheumatoid arthritis (RA) preferentially affects women, with the peak incidence coinciding with estrogen decrease in menopause. Estrogen (E2) may therefore have intrinsic immune-regulatory properties that vanish with menopause. Fc sialylation is a crucial factor determining the inflammatory effector function of antibodies. We therefore analyzed whether E2 affects immunoglobulin G (IgG) sialylation.

    Methods: Postmenopausal (ovariectomized) mice were immunized with ovalbumin and treated with E2 or vehicle. Total and ovalbumin-specific IgG concentrations, sialylation, and Fc. receptor expression were analyzed. Postmenopausal women with RA receiving hormone replacement therapy, including E2, or no treatment were analyzed for IgG sialylation. Furthermore, effects of E2 on the expression of the sialylation enzyme beta-galactoside a2,6-sialyltransferase 1 (St6Gal1) were studied in mouse and human antibody-producing cells.

    Results: E2 treatment significantly increased Fc sialylation of total and ovalbumin-specific IgG in postmenopausal mice. Furthermore, E2 led to increased expression of inhibitory Fc. receptor IIb on bone marrow leukocytes. Treatment with E2 also increased St6Gal1 expression in mouse and human antibody-producing cells, providing a mechanistic explanation for the increase in IgG-Fc sialylation. In postmenopausal women with RA, treatment with E2 significantly increased the Fc sialylation of IgG.

    Conclusions: E2 induces anti-inflammatory effector functions in IgG by inducing St6Gal1 expression in antibodyproducing cells and by increasing Fc sialylation. These observations provide a mechanistic explanation for the increased risk of RA in conditions with low estrogen levels such as menopause.

  • 233.
    Englund, Martin
    et al.
    Lund University, Sweden; Boston University, MA 02215 USA.
    Merkel, Peter A.
    University of Penn, PA 19104 USA.
    Tomasson, Gunnar
    University of Iceland, Iceland.
    Segelmark, Mårten
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för läkemedelsforskning. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Njurmedicinska kliniken US.
    Mohammad, Aladdin J.
    Lund University, Sweden; Addenbrookes Hospital, England.
    Comorbidities in Patients with Antineutrophil Cytoplasmic Antibody-associated Vasculitis versus the General Population2016Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 43, nr 8, s. 1553-1558Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. To evaluate the consultation rates of selected comorbidities in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) compared with the general population in southern Sweden. Methods. We used data from a population-based cohort of patients with AAV diagnosed between 1998 and 2010 in Southern Sweden (701,000 inhabitants). For each patient we identified 4 reference subjects randomly sampled from the general population and matched for year of birth, sex, area of residence, and index year. Using the population-based Skane Healthcare Register, we identified relevant diagnostic codes, registered between 1998 and 2011, for selected comorbidities assigned after the date of diagnosis of AAV or the index date for the reference subjects. We calculated rate ratios for comorbidities (AAV: reference subjects). Results. There were 186 patients with AAV (95 women, mean age 64.5 yrs) and 744 reference persons included in the analysis. The highest rate ratios (AAV: reference) were obtained for osteoporosis (4.6, 95% CI 3.0-7.0), followed by venous thromboembolism (4.0, 95% CI 1.9-8.3), thyroid diseases (2.1, 95% CI 1.3-3.3), and diabetes mellitus (2.0, 95% CI 1.3-2.9). For ischemic heart disease, the rate ratio of 1.5 (95% CI 1.0-2.3) did not reach statistical significance. No statistically significant differences were found for cerebrovascular accidents. Conclusion. AAV is associated with increased consultation rates of several comorbidities including osteoporosis and thromboembolic and endocrine disorders. Comorbid conditions should be taken into consideration when planning and providing care for patients with AAV.

  • 234. Engvall, Inga-Lill
    et al.
    Svensson, Björn
    Boonen, Annelies
    van der Heijde, Désirée
    Lerner, Ulf H
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Hafström, Ingiäld
    Low-dose prednisolone in early rheumatoid arthritis inhibits collagen type I degradation by matrix metalloproteinases as assessed by serum 1CTP--a possible mechanism for specific inhibition of radiological destruction2013Ingår i: Rheumatology, ISSN 1462-0324, E-ISSN 1462-0332, Vol. 52, nr 4, s. 733-742Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To study the effects of low-dose prednisolone on the osteoclast-regulating proteins osteoprotegerin (OPG) and RANK ligand (RANKL) and on markers of bone resorption, 1CTP generated by MMPs and CTX-1 generated by cathepsin K, in patients with early RA in relation to inflammation and joint destruction.

    METHODS: In 225 patients, who at the start of the first DMARD had been randomized to 7.5 mg prednisolone daily for 2 years, the P-group, or no prednisolone, the NoP-group, OPG and RANKL were analysed at 0-24 months and 1CTP and CTX-1 at 0-12 months. Radiographs of hands and feet were assessed at 0, 1 and 2 years using the modified Sharp-van der Heijde score and radiological progression defined as increase in total Sharp score above 5.8. Data were analysed with a mixed linear model and by the GENMOD procedure.

    RESULTS: In the P-group, RANKL and the ratio OPG/RANKL were stable between baseline and 24 months, whereas in the NoP-group, RANKL increased and the ratio OPG/RANKL decreased. CTX-1 decreased significantly more in the P-group. 1CTP decreased over time in both groups, but more in the P-group, P < 0.001, a difference also present in the subgroups of patients in remission. The decrease in 1CTP was associated with less radiological progression after 2 years and displayed a significant interaction with treatment. CONCLUSION: Low-dose prednisolone may inhibit progression of joint destruction by interfering with MMP activity, seen as a marked decrease in 1CTP, as well as by impairing osteoclast activation, shown by a stable OPG/RANKL ratio.

  • 235. Enocsson, Helena
    et al.
    Sjowall, Christopher
    Wirestam, Lina
    Dahle, Charlotte
    Kastbom, Alf
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Wettero, Jonas
    Skogh, Thomas
    Four Anti-dsDNA Antibody Assays in Relation to Systemic Lupus Erythematosus Disease Specificity and Activity2015Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 42, nr 5, s. 817-825Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective. Analysis of antibodies against dsDNA is an important diagnostic tool for systemic lupus erythematosus (SLE), and changes in anti-dsDNA antibody levels are also used to assess disease activity. Herein, 4 assays were compared with regard to SLE specificity, sensitivity, and association with disease activity variables. Methods. Cross-sectional sera from 178 patients with SLE, of which 11 were followed consecutively, from a regional Swedish SLE register were analyzed for immunoglobulin G (IgG) anti-dsDNA by bead-based multiplex assay (FIDIS; Theradig), fluoroenzyme-immunoassay (EliA; Phadia/Thermo Fisher Scientific), Crithidia luciliae immunofluorescence test (CLIFT; ImmunoConcepts), and line blot (EUROLINE; Euroimmun). All patients with SLE fulfilled the 1982 American College of Rheumatology and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) classification criteria. Healthy individuals (n = 100), patients with rheumatoid arthritis (n = 95), and patients with primary Sjogren syndrome (n = 54) served as controls. Results. CLIFT had the highest SLE specificity (98%) whereas EliA had the highest sensitivity (35%). When cutoff levels for FIDIS, EliA, and EUROLINE were adjusted according to SLICC-12 (i.e., double the reference limit when using ELISA), the specificity and sensitivity of FIDIS was comparable to CLIFT. FIDIS and CLIFT also showed the highest concordance (84%). FIDIS performed best regarding association with disease activity in cross-sectional and consecutive samples. Fisher's exact test revealed striking differences between methods regarding associations with certain disease phenotypes. Conclusion. CLIFT remains a good choice for diagnostic purposes, but FIDIS performs equally well when the cutoff is adjusted according to SLICC-12. Based on results from cross-sectional and consecutive analyses, FIDIS can also be recommended to monitor disease activity.

  • 236.
    Enocsson, Helena
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Sjöwall, Christoffer
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Wetterö, Jonas
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för neuro- och inflammationsvetenskap. Linköpings universitet, Medicinska fakulteten.
    Soluble urokinase plasminogen activator receptor: A valuable biomarker in systemic lupus erythematosus?2015Ingår i: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 444, s. 234-241Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Systemic lupus erythematosus (SLE) is a potentially severe autoimmune condition with an unpredictable disease course, often with fluctuations in disease activity over time. Long term inflammation and drug-related side-effects may subsequently lead to permanent organ damage, a consequence which is intimately connected to decreased quality of life and mortality. New lupus biomarkers that convey information regarding inflammation and/or organ damage are thus warranted. Today, there is no clinical biomarker that indicates the risk of damage accrual. Herein we highlight the urokinase plasminogen activator receptor (uPAR) and especially its soluble form (suPAR) that besides having biological functions in e.g. proteolysis, cell migration and tissue homeostasis, recently has emerged as a promising biomarker of inflammation and prognosis of several disorders. A strong association between suPAR and organ damage in SLE was recently demonstrated, and preliminary data (presented in this review) suggests the possibility of a predictive value of suPAR blood levels. The involvement of suPAR in the pathogenesis of SLE remains obscure, but its effects in leukocyte recruitment, phagocytic uptake of dying cells (efferocytosis) and complement regulation suggests that the central parts of the SLE pathogenesis could be regulated by suPAR, and vice versa.

  • 237. Enocsson, Helena
    et al.
    Sjöwall, Christopher
    Kastbom, Alf
    Skogh, Thomas
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Wetterö, Jonas
    Serum C-reactive protein (CRP) associates with lupus disease activity in the absence of measurable interferon alpha and a CRP gene variant2014Ingår i: Arthritis & rheumatology, ISSN 2326-5205, Vol. 66, nr 6, s. 1568-1573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

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

  • 238. Enocsson, Helena
    et al.
    Sjöwall, Christopher
    Skogh, Thomas
    Eloranta, Maija-Leena
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Wetterö, Jonas
    Interferon-alpha Mediates Suppression of C-Reactive Protein Explanation for Muted C-Reactive Protein Response in Lupus Flares?2009Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 60, nr 12, s. 3755-3760Artikel i tidskrift (Refereegranskat)
    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.

  • 239.
    Ericson, Lisa
    et al.
    Nordic Health Economics AB.
    Ambring, Anneli
    Björholt, Ingela
    Dahm, Peter
    Opioid rotation in patients initiated on oxycodone or morphine: a register study.2013Ingår i: Journal of Pain Research, ISSN 1178-7090, E-ISSN 1178-7090, Vol. 6, s. 379-86Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    PURPOSE: Strong opioids are recommended for the treatment of moderate to severe pain. However, some patients do not achieve a successful treatment outcome due to intolerable adverse events and/or inadequate analgesia, thus may benefit from switching to another opioid, a procedure known as "opioid rotation." The type of opioid at treatment initiation may influence the risk of opioid rotation and the objective of this study was to assess such rotation after treatment initiation with two alternative treatments, controlled-release (CR) oxycodone versus CR morphine in patients suffering from non-cancer pain.

    METHOD: The study reported here was a real-life study based on Swedish register data: the Prescribed Drug, National Patient, and Cause of Death registers. The captured data cover the entire Swedish population treated in specialist care. A statistical analysis plan was agreed and signed before data were accessed.

    RESULTS: Data from 50,223 cases were included in the analyses. The risk of rotation was 19% higher in patients initiating treatment with morphine compared with oxycodone (hazard ratio 1.19; 95% confidence interval 1.11-1.27; P < 0.001), after adjusting for such baseline variables that were both significantly correlated with the outcome variable (time to rotation) and significantly different between the groups; age at index date, osteoarthritis and number of pain-related drugs.

    CONCLUSION: Patients with non-cancer pain who initiated treatment with CR morphine had a higher risk of opioid rotation than patients initiated with CR oxycodone.

  • 240.
    Eriksson, Catharina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Immunological mechanisms in systemic autoimmunity: autoantibodies and chemokines in systemic lupus erythematosus and during treatment with TNF inhibitors in rheumatoid arthritis2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background. Rheumatoid Arthritis (RA) is an autoimmune inflammatory disease that, without powerful treatment, may lead to irreversible joint damage. During the past decade, anti-cytokine therapy has become available, e.g., infliximab, a chimeric antibody targeting the pro-inflammatory cytokine TNF that has a central role in the inflammatory process in RA patients. Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease that may affect all organs and is characterized by a massive antibody production. Chemokines, chemokine receptors and lipoprotein receptor-related protein 1(CD91) are regulators of inflammation in autoimmune diseases and T-cell migration.

    Objectives. The aim of this study was to get a deeper understanding how TNF blocking treatment influences inflammatory mechanisms and autoantibody formation in RA with special reference to similarities and differences with SLE.

    Methods. In patients with RA treated with anti-TNF, and in SLE patients (ACR criteria) clinical evaluation was performed and blood samples analyzed. Autoantibodies were analyzed using indirect immunofluorescence, ELISA and multiplex flow cytometry in samples from anti-TNF treated RA patients (n=59) followed longitudinally for 54 weeks, in pre-diseased samples from SLE patients (n=38) and matched population-based controls (n=152). T-cell expression of chemokine receptors and CD91 was analyzed by flow cytometry, whilst serum levels of chemokines were determined using ELISA in anti-TNF treated RA-patients (n=24) followed longitudinally (30 weeks), and cross-sectionally in SLE-patients (n=23). Expression of mRNA for chemokines was analyzed in T-cells from SLE-patients (n=10) using PCR.

    Results. After treatment with infliximab, RA patients produced ANA, anti-dsDNA and anti-nucleosome antibodies, but not anti-ENA antibodies. Although these antibodies are considered typical for SLE only one patient developed a transient lupus-syndrome. Antibodies against cell nuclear antigens, including ENA, were detected several years before the first clinical symptom of SLE; anti-SSA was the earliest detectable antibody.

    In RA-patients before infliximab treatment, the T-cell expression of several chemokine receptors was elevated compared with healthy controls. In contrast, only one soluble chemokine, IP-10 was elevated. After treatment the levels of soluble MIP-1β, MCP-1 and IP-10, and the T-cell expression of CCR2 were decreased. In SLE-patients MIP-1β, MCP-1, SDF-1, IP-10 and RANTES in blood were elevated, whilst expression of CXCR5 and CCR6 on T-cells was lower than in healthy controls. T-cell expression of CXCR2 and CCR1 was elevated in active disease (measured as SLEDAI index), whereas the CXCR5 and CCR2 expression was lower in inactive SLE. In SLE patients with nephritis IP-10 was lower and T-cell expression of CXCR3 and CCR3 elevated compared with patients without nephritis. The expression of CD91 was higher on T-cells from patients not responsive to infliximab treatment compared with responders.

    Conclusion. These findings indicate that anti-TNF (infliximab) treatment in RA-patients has a major impact on the production of autoantibodies and chemokines. The autoantibody profile in infliximab-treated patients was similar to that predating disease onset in SLE patients with the exception of anti-ENA being detectable in SLE, but the development of lupus-syndromes was rare. The expression of CD91 on T-cells may predict responsiveness to infliximab. The expression of chemokine receptors in SLE- patients seemed to be related to disease activity. Anti-nuclear antibodies were detectable years before clinical disease onset in patients who developed SLE suggesting a gradual pathogenic process.

  • 241.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Dahlqvist, Solbritt Rantapää
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Cytokines and Their Relation to Autoantibodies Before Disease Onset in Systemic Lupus Erythematosus2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr 10, s. S286-S287Artikel i tidskrift (Övrigt vetenskapligt)
  • 242.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Eneslätt, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Ivanoff, J
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, Karl-Gösta
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus2003Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 12, nr 10, s. 766-774Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The expression of chemokine receptors on T-cells and chemokine levels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P = 0.051 and P = 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI &GE; 6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P = 0.001 and P = 0.01, respectively) and with controls ( P = 0.02 and P = 0.053, respectively). The levels of the chemokines MIP-1β MCP-1, SDF-1α, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P = 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P = 0.025) and compared with controls (P = 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/ serum.

  • 243.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Engstrand, S
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, K-G
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF alpha2005Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 64, nr 3, s. 403-407Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Research on autoantibody formation in patients treated with TNFα inhibitors has produced contradictory results.

    Objective: To study the prevalence of autoantibodies in patients with rheumatoid arthritis treated with the TNFα inhibitor infliximab.

    Methods: 53 patients (48 female, 11 male) treated with infliximab for rheumatoid arthritis were followed for autoantibody production before treatment and after 14, 30, and 54 weeks. Six patients treated with etanercept were studied for comparison. The analyses included antibodies against nuclear antigens (ANA), extractable nuclear antigens, double stranded (ds)DNA (by ELISA, IIF on Crithidia luciliae for IgM and IgG, and Farr assay), nucleosomes, cardiolipin, smooth muscle, mitochondria, proteinase 3, and myeloperoxidase antigens.

    Results: The number of patients treated with infliximab who developed antibodies against dsDNA of both IgG and IgM class (tested by IIF) increased significantly. The prevalence of patients positive for IgG class increased to 66% at 30 weeks and 45% at 54 weeks, and of IgM class to 85% and 70%, respectively. The titre and number of patients expressing antibodies against nucleosomes and ANA also increased significantly. The number of rheumatoid factor or anticardiolipin positive patients was stable and there was no increase in antibodies against the other antigens. A lupus-like syndrome was seen in one patient. No patient treated with etanercept developed any of these autoantibodies.

    Conclusions: Patients treated with infliximab may develop anti-dsDNA antibodies of both IgM and IgG class, anti-nucleosome antibodies, and ANA, with a gradual increase until 30 weeks.

  • 244.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Johansson, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Wadell, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Virologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Autoantibodies predate the onset of Systemic Lupus Erythematosus in northern Sweden2011Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 13, nr 1, s. R30-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Autoantibodies have a central role in systemic lupus erythematosus (SLE). The presence of autoantibodies preceding disease onset by years has been reported both in patients with SLE and those with rheumatoid arthritis, suggesting a gradual development of these diseases. To identify autoantibodies in a Northern European population predating the onset of symptoms of SLE and their relationship to presenting symptoms.

    METHODS: The register of patients fulfilling the American College of Rheumatology (ACR) criteria for SLE and with a given date for the onset of symptoms was co-analysed with the register of the Medical Biobank, Umea, Sweden. Thirty-eight patients were identified as having donated blood samples prior to symptom onset. A nested case-control study (1:4) was performed with 152 age- and sex-matched controls identified from within the Biobank register. Antibodies against anti- Sjogren's syndrome antigen A (Ro/SSA) (60 and 52 kDa), anti- Sjogren's syndrome antigen B (La/SSB), anti-Smith antibody (Sm), ribonucleoprotein (RNP), scleroderma-70 (Scl-70), anti- histidyl-tRNA synthetase antibody (Jo-1), double-stranded DNA (dsDNA); Centromere protein B and histones were analysed using the anti-nuclear antibody test II (ANA-II) Plus Test System (Athena Multi-Lyte(R)) on a Bio-Plex Array Reader (Luminex200). ANA were analysed using indirect immunofluorescence on Human Epidermal cells-2 (HEp2-cells) at a sample dilution of 1:100.

    RESULTS: Autoantibodies against nuclear antigens were detected 5.6 (+/- 4.7; mean +/- SD) years before the onset of symptoms and 8.7 (+/- 5.6) years before diagnosis in 63% of the individuals who subsequently developed SLE. The sensitivity (45.7%) was highest for ANA with a specificity of 95%, followed by anti-dsDNA and anti-Ro/SSA antibodies both with sensitivities of 20.0% at specificities of 98.7% and 97.4%, respectively. The odds ratio (OR) for anti-dsDNA predicting disease was 18.13 (CI 95%; 3.58-91.84), and for ANA 11.5 (CI 95%; 4.54-28.87). Anti-Ro/SSA antibodies appeared first, 6.6 (+/- 2.5) years prior to symptom onset. The mean number of autoantibodies in pre-diseased individuals was 1.4 and after disease onset 3.1 (P< 0.0005). The time predating disease was shorter, and the number of autoantibodies greater, in those individuals with serositis as a presenting symptom in comparison to those with arthritis and skin manifestations.

    CONCLUSIONS: Autoantibodies against nuclear antigens were detected in individuals developing SLE several years before the onset of symptoms and diagnosis. The most sensitive autoantibodies were ANA, Ro/SSA and dsDNA, with the highest predictive OR for anti-dsDNA antibodies. The first autoantibodies detected were anti-Ro/SSA.

  • 245.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus2014Ingår i: Lupus, ISSN 0961-2033, E-ISSN 1477-0962, Vol. 23, nr 7, s. 691-696Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Methods: Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age-and sex-matched controls were also identified. The concentrations of interferon-a, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. Results: The interferon-g inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p < 0.05) and correlated with interferon-a (p < 0.01). The interferon-g inducible protein-10 and interferon-a concentrations were significantly increased in individuals positive for autoantibodies: interferon-g inducible protein-10 for ANA; anti-SSA/Ro and anti-Jo-1 antibodies; interferon-a with anti-SSB/La antibodies. The levels of interleukin-10, interferon-g inducible protein-10 and monocyte chemotactic protein-1 increased significantly from the pre-symptomatic individuals to after onset of systemic lupus erythematosus. Conclusions: An increased concentration of interferon-gamma inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-gamma inducible protein-10 and interferon-alpha were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation.

  • 246.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, Karl-Gösta
    Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institute at Karolinska University Hospital, Huddinge, Stockholm, Sweden.
    T-cell expression of CD91: a marker of unresponsiveness to anti-TNF therapy in rheumatoid arthritis2010Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 118, nr 11, s. 837-845Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to investigate the expression of thrombospondin-1 (TSP-1) and its receptors, lipoprotein receptor-related protein/cluster of differentiation (CD)91, calreticulin (CRT), and CD47, on T cells and monocytes from patients with rheumatoid arthritis (RA) treated with anti-tumor necrosis factor (TNF) therapy. The surface expression of CD91 and associated components on CD3- and CD14-positive cells was examined using flow cytometry in 12 patients with established RA before and after beginning therapy and compared with that of 9 healthy controls and 12 patients with early RA treated with conventional therapies. CD3-positive cells from anti-TNF non-responders showed significantly greater expression of CD91 expression than those from responders (p<0.05) after 6 weeks and when all measurements were pooled (p<0.001). CD91 expression on CD3-positive cells from non-responders to other therapies was at the same level as in healthy controls. In contrast, CD14-positive cells showed no differences in CD91 expression between patients and controls or between responders and non-responders to anti-TNF therapy. The expression of TSP-1, CRT, and CD47 showed no differences between responders and non-responders. The results suggest T-lymphocyte expression of CD91 to be a biomarker that signifies unresponsiveness to anti-TNF therapy in patients with RA and may be used to identify potential responders and non-responders.

  • 247.
    Eriksson, Catharina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk immunologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Sundqvist, KG
    Changes in chemokines and their receptors in blood during treatment with the TNF inhibitor infliximab in patients with rheumatoid arthritis2013Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 42, nr 4, s. 260-265Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background. Chemokines are involved in leucocyte recruitment into inflammatory sites, such as the synovial tissue of patients with rheumatoid arthritis (RA). The release of certain chemokines is augmented by pro-inflammatory cytokines, such as tumor necrosis factor (TNF). Infliximab, a monoclonal antibody against TNF that blocks the biological effects of TNF, is used in the treatment of chronic inflammatory diseases. The effect of blocking TNF activity on chemokines is not fully understood.

    Aim. The aim of this study was to analyse the effects on chemokines and their receptors on peripheral mononuclear cells of anti-TNF treatment in RA-patients.

    Material and methods. Twelve patients with established RA who began treatment with infliximab, and nine patients with early RA treated with traditional disease-modifying anti-rheumatic drugs, were followed clinically for 30 weeks and chemokine levels in blood samples and chemokine receptor expression on the surface of T-cells and monocytes analysed. Three SLE-patients, as a small control group of another inflammatory disease, and nine healthy subjects were also included in the study.

    Result. CXCL10/IP-10 was significantly higher in RA-patients compared with healthy controls and decreased significantly two weeks after infliximab infusion. CCL2/MCP-1 and CCL4/MIP-1β decreased significantly after infliximab treatment although the concentrations were not significantly elevated at baseline compared with controls. There was an inverse correlation between the chemokine cleaving molecule dipeptidyl peptidase-IV/CD26 and CCL5/RANTES. Several chemokine receptors on T-cells were elevated in RA patients at inclusion into the study. The CCR2 expression on T-cells decreased significantly after infliximab treatment.

    Conclusion. The chemokines CXCL10/IP-10, CCL2/MCP-1 and CCL4/MIP-1β, mainly targeting the Th1 immune response, decreased after treatment with anti-TNF suggesting a more pronounced effect onTh1 activity than on the Th2 mediated response. Several chemokine receptors on blood T-cells were elevated in RA-patients, suggesting that they may be involved in the recruitment of T-lymphocytes from the blood to affected tissues.

  • 248.
    Eriksson, D.
    et al.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden.
    Bianchi, M.
    Uppsala University, Sweden.
    Landegren, N.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Nordin, J.
    Uppsala University, Sweden.
    Dalin, F.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Mathioudaki, A.
    Uppsala University, Sweden.
    Eriksson, G. N.
    Karolinska Institute, Sweden.
    Hultin-Rosenberg, L.
    Uppsala University, Sweden.
    Dahlqvist, J.
    Uppsala University, Sweden.
    Zetterqvist, H.
    Uppsala University, Sweden; Uppsala University, Sweden.
    Karlsson, A.
    Uppsala University, Sweden.
    Hallgren, A.
    Karolinska Institute, Sweden; Uppsala University, Sweden.
    Farias, F. H. G.
    Uppsala University, Sweden.
    Muren, E.
    Uppsala University, Sweden.
    Ahlgren, K. M.
    Uppsala University, Sweden.
    Lobell, A.
    Uppsala University, Sweden.
    Andersson, G.
    Swedish University of Agriculture Science, Sweden.
    Tandre, K.
    Uppsala University, Sweden.
    Dahlqvist, S. R.
    Umeå University, Sweden.
    Söderkvist, Peter
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Diagnostikcentrum, Klinisk patologi och klinisk genetik.
    Rönnblom, L.
    Uppsala University, Sweden.
    Hulting, A. -L.
    Karolinska Institute, Sweden.
    Wahlberg Topp, Jeanette
    Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för kardiovaskulär medicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Endokrinmedicinska kliniken.
    Ekwall, O.
    University of Gothenburg, Sweden.
    Dahlqvist, P.
    Umeå University, Sweden.
    Meadows, J. R. S.
    Uppsala University, Sweden.
    Bensing, S.
    Metab and Diabet Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Lindblad-Toh, K.
    Uppsala University, Sweden; Broad Institute MIT and Harvard, MA USA.
    Kampe, O.
    Karolinska Institute, Sweden; Metab and Diabet Karolinska University Hospital, Sweden; Uppsala University, Sweden.
    Pielberg, G. R.
    Uppsala University, Sweden.
    Extended exome sequencing identifies BACH2 as a novel major risk locus for Addisons disease2016Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 286, nr 6, s. 595-608Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundAutoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addisons disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology. MethodsTo understand the genetic background of Addisons disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addisons disease and 1394 controls. ResultsWe identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 x 10(-15), MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addisons disease development. We also confirmed the previously known associations with the HLA complex. ConclusionWhilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addisons disease, we have identified BACH2 as a major risk locus in Addisons disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.

  • 249. Eriksson, Daniel
    et al.
    Bianchi, Matteo
    Landegren, Nils
    Dalin, Frida
    Skov, Jakob
    Hultin-Rosenberg, Lina
    Mathioudaki, Argyri
    Nordin, Jessika
    Hallgren, Åsa
    Andersson, Göran
    Tandre, Karolina
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Söderkvist, Peter
    Rönnblom, Lars
    Hulting, Anna-Lena
    Wahlberg, Jeanette
    Dahlqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Ekwall, Olov
    Meadows, Jennifer R. S.
    Lindblad-Toh, Kerstin
    Bensing, Sophie
    Pielberg, Gerli Rosengren
    Kämpe, Olle
    Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison's disease in Sweden2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, artikel-id 8395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.

  • 250.
    Eriksson, Daniel
    et al.
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden.
    Dalin, Frida
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    Eriksson, Gabriel Nordling
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Landegren, Nils
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    Bianchi, Matteo
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Hallgren, Åsa
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden.
    Dahlqvist, Per
    Umeå Univ, Dept Publ Hlth & Clin Med, Umeå, Sweden.
    Wahlberg, Jeanette
    Linköping Univ, Dept Endocrinol, Linköping, Sweden; Linköping Univ, Dept Med & Hlth Sci, Linköping, Sweden; Linköping Univ, Dept Clin & Expt Med, Linköping, Sweden.
    Ekwall, Olov
    Univ Gothenburg, Dept Pediat, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden; Univ Gothenburg, Dept Rheumatol & Inflammat Res, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Winqvist, Ola
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.
    Catrina, Sergiu-Bogdan
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hulting, Anna-Lena
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Lindblad-Toh, Kerstin
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Alimohammad, Mohammad
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Dermatologi och venereologi.
    Husebye, Eystein S
    Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden; Univ Bergen, Dept Clin Sci, Bergen, Norway; Univ Bergen, Dept Med, Bergen, Norway; KG Jebsen Ctr Autoimmune Disorders, Bergen, Norway.
    Knappskog, Per Morten
    Univ Bergen, Dept Clin Sci, Bergen, Norway; Haukeland Hosp, Ctr Med Genet & Mol Med, Bergen, Norway.
    Pielberg, Gerli Rosengren
    Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bensing, Sophie
    Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden; Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden .
    Kämpe, Olle
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Ctr Mol Med, Stockholm, Sweden; Karolinska Univ Hosp, Dept Endocrinol Metab & Diabet, Stockholm, Sweden; KG Jebsen Ctr Autoimmune Disorders, Bergen, Norway.
    Cytokine Autoantibody Screening in the Swedish Addison Registry Identifies Patients With Undiagnosed APS12018Ingår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 103, nr 1, s. 179-186Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Context: Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features autoimmune Addison disease as a major component. Although APS1 accounts for only a small fraction of all patients with Addison disease, early identification of these individuals is vital to prevent the potentially lethal complications of APS1.

    Objective: To determine whether available serological and genetic markers are valuable screening tools for the identification of APS1 among patients diagnosed with Addison disease.

    Design: We systematically screened 677 patients with Addison disease enrolled in the Swedish Addison Registry for autoantibodies against interleukin-22 and interferon-α4. Autoantibody-positive patients were investigated for clinical manifestations of APS1, additional APS1-specific autoantibodies, and DNA sequence and copy number variations of AIRE.

    Results: In total, 17 patients (2.5%) displayed autoantibodies against interleukin-22 and/or interferon-α4, of which nine were known APS1 cases. Four patients previously undiagnosed with APS1 fulfilled clinical, genetic, and serological criteria. Hence, we identified four patients with undiagnosed APS1 with this screening procedure.

    Conclusion: We propose that patients with Addison disease should be routinely screened for cytokine autoantibodies. Clinical or serological support for APS1 should warrant DNA sequencing and copy number analysis of AIRE to enable early diagnosis and prevention of lethal complications.

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