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  • 101.
    Björk, Mathilda
    Linköpings universitet, Hälsouniversitetet.
    Aspects of disability in early rheumatoid arthritis: a five-year follow-up in the Swedish TIRA project2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Rheumatoid arthritis (RA) is a progressive disease, often leading to disability. Because the disease course develops rapidly during the first years after diagnosis, more knowledge is needed about the early disease course to minimize later disability. This thesis describes the course of disability in early RA such as hand function, pain intensity, activity limitation and sick leave. In addition, this thesis compares disability between women and men and compares disability between RA patients and referents.

     

    This thesis is primarily based on data from the 320 patients that were included in the multi-centre project in Sweden called ‘Early interventions in rheumatoid arthritis’ (TIRA). A wide range of outcome variables was registered between 1996 and 2006 during regular follow-ups from time for diagnosis through the eight-year follow-up. Outcome regarding disease activity and disability of RA patients still remaining in TIRA at the three and five year follow-up respectively are used in this thesis. Data concerning sick leave were obtained for the patients during six years (1993-2001) – three years before and three years after diagnosis. Referents were included in two of the studies. Data regarding disability in referents were obtained according to hand function and activity limitation using the Health Assessment Questionnaire (HAQ). Data for sick leave were obtained for six years in referents, for the same period as the RA patients.

    For most variables, disability in RA was most pronounced at time of diagnosis but before intervention started. Disability was then reduced already at the 3-month follow-up and thereafter affected but stable during the following five years. The exception was participation, reflected by sick leave, a variable that was stable from inclusion to three years from diagnosis. Activity limitation, pain intensity and sick leave in RA that represents different aspects of disability were explained by other aspects of disability and contextual factors rather than by disease activity. RA affects women and men differently in some aspects. Women had more severe course of activity limitations than men according to HAQ. Men were more affected than women in range of motion, although the differences were small in a clinical perspective. However, pain intensity and frequency of sick leave did not differ between women and men. Patients with RA have pronounced disability in relation to referents although several variables improve soon after diagnosis. This discrepancy refers to hand function as well as activity limitations and sick leave. The frequency of sick leave increased during the year before diagnosis in relation to referents and was thereafter high compared to sick leave in referents.

  • 102.
    Björk, Mathilda
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Rehabiliteringsmedicin. Linköpings universitet, Hälsouniversitetet.
    Aspects of Disability in Rheumatoid Arthritis: a five-year follow-up in the Swedish TIRA project2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Rheumatoid arthritis (RA) is a progressive disease, often leading to disability. Because the disease course develops rapidly during the first years after diagnosis, more knowledge is needed about the early disease course to minimize later disability. This thesis describes the course of disability in early RA such as hand function, pain intensity, activity limitation and sick leave. In addition, this thesis compares disability between women and men and compares disability between RA patients and referents.

    This thesis is primarily based on data from the 320 patients that were included in the multi-centre project in Sweden called ‘Early interventions in rheumatoid arthritis’ (TIRA). A wide range of outcome variables was registered between 1996 and 2006 during regular follow-ups from time for diagnosis through the eight-year follow-up. Outcome regarding disease activity and disability of RA patients still remaining in TIRA at the three and five year follow-up respectively are used in this thesis. Data concerning sick leave were obtained for the patients during six years (1993-2001) – three years before and three years after diagnosis. Referents were included in two of the studies. Data regarding disability in referents were obtained according to hand function and activity limitation using the Health Assessment Questionnaire (HAQ). Data for sick leave were obtained for six years in referents, for the same period as the RA patients.

    For most variables, disability in RA was most pronounced at time of diagnosis but before intervention started. Disability was then reduced already at the 3-month follow-up and thereafter affected but stable during the following five years. The exception was participation, reflected by sick leave, a variable that was stable from inclusion to three years from diagnosis. Activity limitation, pain intensity and sick leave in RA that represents different aspects of disability were explained by other aspects of disability and contextual factors rather than by disease activity. RA affects women and men differently in some aspects. Women had more severe course of activity limitations than men according to HAQ. Men were more affected than women in range of motion, although the differences were small in a clinical perspective. However, pain intensity and frequency of sick leave did not differ between women and men. Patients with RA have pronounced disability in relation to referents although several variables improve soon after diagnosis. This discrepancy refers to hand function as well as activity limitations and sick leave. The frequency of sick leave increased during the year before diagnosis in relation to referents and was thereafter high compared to sick leave in referents.

  • 103.
    Björk, Mathilda
    et al.
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Avdelningen för arbetsterapi. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Thyberg, Ingrid
    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.
    Valtersson, Eva
    Linköpings universitet, Institutionen för medicin och hälsa. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Östlund, Gunnel
    School of Health Care and Social Welfare, Mälardalen University, Eskilstuna, Sweden.
    Stenström, Birgitta
    Region Östergötland, Hjärt- och Medicincentrum, Reumatologiska kliniken i Östergötland.
    Sverker, Annette
    Linköpings universitet, Institutionen för samhälls- och välfärdsstudier, Socialt arbete. Linköpings universitet, Filosofiska fakulteten. Linköpings universitet, Institutionen för medicin och hälsa, Avdelningen för samhällsmedicin. Linköpings universitet, Medicinska fakulteten. Region Östergötland, Närsjukvården i centrala Östergötland, Rörelse och Hälsa.
    Foot barriers in patients with early rheumatoid arthritis: an interview study among Swedish women and men2018Ingår i: Arthritis care & research, ISSN 2151-464X, E-ISSN 2151-4658, Vol. 70, nr 9, s. 1348-1354Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Foot impairments are related to reduced mobility and participation restrictions in daily activities in patients with established rheumatoid arthritis (RA). The new biological medications are effective and reduce disease activity, but not disability to the same extent. Foot impairments are assumed to be related to participation restrictions also in patients with early RA, diagnosed after the introduction of biological medications. The knowledge of foot impairments needs to be more explored after the introduction of biological disease-modifying drugs (bDMARDs). The aim of this study was to explore the patients' perspective of foot impairments related to early RA.

    METHODS: The sample included 59 patients (20-63 years) who were interviewed about participation dilemmas in daily life using the Critical Incident Technique. The interviews were audio-recorded and transcribed. Data related to foot impairments were extracted and analyzed thematically. A research partner validated the analysis. The study was approved by the Regional Ethics Committee.

    RESULTS: Patients with early RA described a variety of participation restrictions related to foot impairments: 1) foot hindrances in domestic life, 2) foot impairments influencing work, 3) leisure activities restricted by one's feet 4) struggling to be mobile 5) foot impairments as an early sign of rheumatic disease.

    CONCLUSION: There is a need to focus on foot impairments related to early RA, and for health care professionals to understand these signs. A suggestion for future research is to conduct a longitudinal follow-up of foot impairment related to medication, disease activity and disability in patients diagnosed after the introduction of bDMARDs. This article is protected by copyright. All rights reserved.

  • 104.
    Björk Wilhelms, Daniel
    et al.
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Mirrasekhian, Elahe
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Engblom, David
    Linköpings universitet, Institutionen för klinisk och experimentell medicin, Avdelningen för cellbiologi. Linköpings universitet, Hälsouniversitetet.
    Cyclooxygenase isoform exchange blocks inflammatory symptoms2014Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Cyclooxygenase‐2 (COX‐2) is the main source of inducible prostaglandin E2 production and mediates inflammatory symptoms including fever, loss of appetite and hyperalgesia. In contrast, COX‐1 is dispensable for most inflammatory symptoms. Global deletion of COX‐2 leads to a blockade of inflammation‐induced fever and appetite loss but also to high rates of fetal mortality. The latter is unfortunate since mice without COX‐2 are powerful tools in the study of inflammation and cardiovascular medicine. The differential functionality of the COX isoforms could be due to differences in regulatory regions of the genes, leading to different expression patterns, or to differences in the coding sequence, leading to distinct functional properties of the proteins. To study this in the context of inflammatory symptoms, we used mice in which the coding sequence of COX‐2 was replaced by the corresponding sequence of COX‐1. In these mice, COX‐1 mRNA was induced by inflammation but COX‐1 protein expression did not fully mimic inflammation‐induced COX‐2 expression. Just like mice globally lacking COX‐2, these mice showed a complete lack of fever and inflammation‐induced anorexia. However, as previously reported, they displayed close to normal survival rates. This shows that the COX activity generated from the hybrid gene was strong enough to allow survival but not strong enough to mediate inflammatory symptoms, making the line an interesting alternative to COX‐2 knockouts for the study of inflammation. Our results also show that the functional differences between COX‐1 and COX‐2 in the context of inflammatory symptoms is not only dependent on the features of the promoter regions. Instead they indicate that there are fundamental differences between the isoforms at translational or posttranslational levels, which make hybrid genes less functional.

  • 105.
    Björsenius, Isak
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Atherosclerotic Burden in Patients with Rheumatoid Arthritis is Partially Reflected by Disease Severity at the Time of Diagnosis - 11 Years of Prospective Follow Up2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 106.
    Blomgran, Robert
    et al.
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Patcha Brodin, Veronika
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Verma, Deepti
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Bergström, Ida
    Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Sjöwall, Christopher
    Division of Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Eriksson, Per
    Division of Rheumatology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
    Lerm, Maria
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden; Center for Infectious Medicine, Karolinska Institute Huddinge, Stockholm, Sweden .
    Stendahl, Olle
    Division of Medical Microbiology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden .
    Särndahl, Eva
    Örebro universitet, Institutionen för hälsovetenskap och medicin. Department of Clinical Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Common genetic variations in the NALP3 inflammasome are associated with delayed apoptosis of human neutrophils2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 3, artikel-id e31326Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages.

    Methods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients' neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response.

    Conclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.

  • 107. Bokarewa, M
    et al.
    Brink, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Erlandsson, M
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Survivin but NOT fms-like tyrosine kinase ligand (FLT3L) is up-regulated before onset of rheumatoid arthritis2013Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 72, nr Suppl. 3, s. 193-193Artikel i tidskrift (Refereegranskat)
  • 108. Bokarewa, Maria
    et al.
    Brink, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Erlandsson, Malin
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Survivin but not Fms-like tyrosine kinase 3 ligand is up-regulated before the onset of rheumatoid arthritis: a pilot study2014Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 16, nr 1, s. R45-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Antibodies against citrullinated peptides (anti-CCP) and increased levels of cytokines precede the development of rheumatoid arthritis (RA) by several years. Recently, the proteins survivin and Fms-like tyrosine kinase 3 ligand (Flt3L) have been identified as biomarkers of RA associated with joint destruction. Our objective was to investigate the potential of survivin and Flt3L as predictors of RA in samples from patients prior to onset of symptoms. Methods: This study included 47 individuals sampled before onset of RA (median 2.5 years (IQR 4.5) and 155 matched controls, all were donors to the Medical Biobank of Northern Sweden, and 36 RA patients. Levels of anti-CCP, survivin and Flt3L were measured using ELISAs and 29 cytokines/chemokines by multiplex detection. Results: Levels of survivin were increased in pre-symptomatic individuals compared with controls (P = 0.003), whilst the levels of Flt3L were similar. The frequency of survivin positivity in the pre-symptomatic individuals was increased compared with the controls (36.2 vs. 14.2%, P = 0.001) and predicted disease development (odds ratio (OR) = 3.4 (95% confidence interval (CI) 1.6-7.2)). The frequency of survivin and Flt3L in RA patients was increased compared with the controls (both, P < 0.0001, OR = 12.1 (95% CI, 5.3-27.6) and OR = 11.0 (95% CI, 3.9-30.9), respectively). Anti-CCP positive pre-symptomatic individuals and patients had significantly higher levels of survivin compared with anti-CCP2 negative individuals. In pre-symptomatic individuals, survivin correlated with IL-12, IL-1 beta and IL-9 whereas Flt3L correlated to a significantly broader spectrum of cytokines in RA patients. Conclusion: Proto-oncogene survivin was increased in individuals prior to onset of symptoms of RA and was correlated to cytokines suggesting its role at pre-clinical stages of the disease.

  • 109.
    Bolin, Karin
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Leonard, Dag
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Gunnarsson, I.
    Sjowall, C.
    Eriksson, P.
    Forsblad-d'Elia, H.
    Jonsen, A.
    Theander, E.
    Omdal, R.
    Jonsson, R.
    Sivils, K.
    Wahren-Herlenius, M.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Early B Cell Factor 1 is Associated to Clinical Manifestations in Primary Sjogren's Syndrome and SLE2015Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 81, nr 5, s. 416-416Artikel i tidskrift (Övrigt vetenskapligt)
  • 110. Bolstad, Anne Isine
    et al.
    Le Hellard, Stephanie
    Kristjansdottir, Gudlaug
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Vasaitis, Lilian
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Kvarnström, Marika
    Sjöwall, Christopher
    Johnsen, Svein Joar Auglænd
    Eriksson, Per
    Omdal, Roald
    Brun, Johan G
    Wahren-Herlenius, Marie
    Theander, Elke
    Syvänen, Ann-Christine
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Molekylär medicin.
    Rönnblom, Lars
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper.
    Jonsson, Roland
    Association between genetic variants in the tumour necrosis factor/lymphotoxin α/lymphotoxin β locus and primary Sjogren's syndrome in Scandinavian samples2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr 6, s. 981-988Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES:

    Lymphotoxin β (LTB) has been found to be upregulated in salivary glands of patients with primary Sjögren's syndrome (pSS). An animal model of pSS also showed ablation of the lymphoid organisation and a marked improvement in salivary gland function on blocking the LTB receptor pathway. This study aimed to investigate whether single-nucleotide polymorphisms (SNP) in the lymphotoxin α (LTA)/LTB/tumour necrosis factor (TNF) gene clusters are associated with pSS.

    METHODS:

    527 pSS patients and 532 controls participated in the study, all of Caucasian origin from Sweden and Norway. 14 SNP markers were genotyped and after quality control filtering, 12 SNP were analysed for their association with pSS using single marker and haplotype tests, and corrected by permutation testing.

    RESULTS:

    Nine markers showed significant association with pSS at the p=0.05 level. Markers rs1800629 and rs909253 showed the strongest genotype association (p=1.64E-11 and p=4.42E-08, respectively, after correcting for sex and country of origin). When the analysis was conditioned for the effect of rs1800629, only the association with rs909253 remained nominally significant (p=0.027). In haplotype analyses the strongest effect was observed for the haplotype rs909253G_rs1800629A (p=9.14E-17). The associations were mainly due to anti-Ro/SSA and anti-La/SSB antibody-positive pSS.

    CONCLUSIONS:

    A strong association was found between several SNP in the LTA/LTB/TNFα locus and pSS, some of which led to amino acid changes. These data suggest a role for this locus in the development of pSS. Further studies are needed to examine if the genetic effect described here is independent of the known genetic association between HLA and pSS.

  • 111.
    Boman, Antonia
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Prediction of Joint Destruction in Early Rheumatoid Arthritis: RANKL but not Sclerostin or Gene Polymorphisms is Related to Joint Destruction in Early Rheumatoid Arthritis2017Självständigt arbete på grundnivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
  • 112.
    Boman, Antonia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Berglin, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL) and Sclerostin Are Related to Joint Destruction in Early Rheumatoid Arthritis Unrelated to Polymorphisms of the Genes2015Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, E-ISSN 2326-5205, Vol. 67, nr 10, artikel-id 3101Artikel i tidskrift (Övrigt vetenskapligt)
  • 113.
    Boman, Antonia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Kokkonen, Heidi
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Berglin, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Receptor activator of nuclear factor kappa-B ligand (RANKL) but not sclerostin or gene polymorphisms is related to joint destruction in early rheumatoid arthritis2017Ingår i: Clinical Rheumatology, ISSN 0770-3198, E-ISSN 1434-9949, Vol. 35, nr 5, s. 1005-1012Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to analyze relationships between receptor activator of nuclear factor kappa-B (RANKL), sclerostin and their gene polymorphisms with radiological progression in patients with early rheumatoid arthritis (RA). Patients with early RA (n = 407, symptomatic <1 year) (ARA criteria) examined radiologically at inclusion and after 24 months were consecutively included. Disease activity score and C-reactive protein were regularly recorded. Sclerostin, RANKL, and anti-CCP2 antibodies were analyzed in plasma at baseline using ELISAs. Data on gene polymorphism for sclerostin and RANKL were extracted from Immunochip analysis. Sex- and age-matched controls (n = 71) were identified from the Medical Biobank of Northern Sweden. The concentration of RANKL was significantly higher in patients compared with controls, median (IQR) 0.56 (0.9) nmol/L and 0.20 (0.25) nmol/L (p < 0.001), and in anti-CCP2-positive patients compared with sero-negative individuals. Sclerostin was significantly increased in female patients 0.59 (0.47-0.65) ng/mL compared with female controls 0.49 (0.4-0.65) ng/mL (p < 0.02). RANKL concentration was related to the Larsen score at baseline (p < 0.01), after 24 months (p < 0.001), and to radiological progression at 24 months (p < 0.001). Positivity of RANKL and anti-CCP2 yielded significant risk for progression with negativity for both as reference. No single nucleotide polymorphism encoding TNFSF11 or SOST was associated with increased concentrations of the factors. The concentration of RANKL was related to the Larsen score at baseline, at 24 months, and radiological progression at 24 months particularly in anti-CCP2-positive patients, while the concentration of sclerostin was unrelated to radiological findings.

  • 114. Bos, Wouter H.
    et al.
    van de Stadt, Lotte A.
    Sohrabian, Azita
    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.
    van Schaardenburg, Dirkjan
    Development of anti-citrullinated protein antibody and rheumatoid factor isotypes prior to the onset of rheumatoid arthritis2014Ingår i: ARTHRITIS RES THER, ISSN 1478-6354, Vol. 16, nr 2, s. 405-Artikel i tidskrift (Refereegranskat)
  • 115. Boström, Elisabeth Almer
    et al.
    d'Elia, Helena Forsblad
    Dept of Rheumatology and Inflammation Research, Sahlgrenska Academy, Göteborgs universitet.
    Dahlgren, Ulf
    Simark-Mattsson, Charlotte
    Hasséus, Bengt
    Carlsten, Hans
    Tarkowski, Andrej
    Bokarewa, Maria
    Salivary resistin reflects local inflammation in Sjögren's syndrome.2008Ingår i: Journal of Rheumatology, ISSN 0315-162X, E-ISSN 1499-2752, Vol. 35, nr 10, s. 2005-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: To assess the role of resistin in primary Sjögren's syndrome (pSS) and its relation to local inflammation.

    METHODS: Blood and saliva were collected from 37 patients with pSS (duration of symptoms 12.6+/-1 yrs) and 32 healthy controls. Expression of resistin in salivary glands was visualized immunohistologically, and levels of resistin were detected by ELISA. Levels of resistin were evaluated at baseline and following oral dehydroepiandrosterone (DHEA) treatment (50 mg/day). The effect of DHEA treatment on the secretion of resistin was assessed in vitro in human leukocytes after challenge with insulin and lipopolysaccharide.

    RESULTS: Levels of resistin in saliva were significantly higher in patients with pSS than in controls, while circulating levels of resistin were similar in both groups. Resistin was expressed in the epithelial cells of striated ducts and in the lymphocytic foci. Resistin levels in saliva were related to the intensity of inflammation in the minor salivary glands of pSS patients. No changes of the levels of resistin in blood or saliva were observed during DHEA treatment. Exposure of naive leukocytes to DHEA in vitro induced significant expression of resistin compared to nonstimulated peripheral blood mononuclear cells (p=0.031).

    CONCLUSION: We showed that levels of resistin are upregulated locally in the salivary glands of patients with pSS; and that the levels of resistin correspond to the intensity of lymphocytic inflammation in patients with pSS. We suggest that resistin is expressed in the salivary glands of patients with pSS and may be a driving factor of local inflammation.

  • 116. Bottai, Matteo
    et al.
    Tjärnlund, Anna
    Santoni, Giola
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Centrum för forskning om äldre och åldrande (ARC), (tills m KI).
    Werth, Victoria P.
    Pilkington, Clarissa
    de Visser, Marianne
    Alfredsson, Lars
    Amato, Anthony A.
    Barohn, Richard J.
    Liang, Matthew H.
    Singh, Jasvinder A.
    Aggarwal, Rohit
    Arnardottir, Snjolaug
    Chinoy, Hector
    Cooper, Robert G.
    Danko, Katalin
    Dimachkie, Mazen M.
    Feldman, Brian M.
    García-De La Torre, Ignacio
    Gordon, Patrick
    Hayashi, Taichi
    Katz, James D.
    Kohsaka, Hitoshi
    Lachenbruch, Peter A.
    Lang, Bianca A.
    Li, Yuhui
    Oddis, Chester V.
    Olesinka, Marzena
    Reed, Ann M.
    Rutkowska-Sak, Lidia
    Sanner, Helga
    Selva-O'Callaghan, Albert
    Song, Yeong Wook
    Vencovsky, Jiri
    Ytterberg, Steven R.
    Miller, Frederick W.
    Rider, Lisa G.
    Lundberg, Ingrid E.
    EULAR/ACR classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups: a methodology report2017Ingår i: RMD Open, E-ISSN 2056-5933, Vol. 3, nr 2, artikel-id e000507Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To describe the methodology used to develop new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIMs) and their major subgroups.

    Methods An international, multidisciplinary group of myositis experts produced a set of 93 potentially relevant variables to be tested for inclusion in the criteria. Rheumatology, dermatology, neurology and paediatric clinics worldwide collected data on 976 IIM cases (74% adults, 26% children) and 624 non-IIM comparator cases with mimicking conditions (82% adults, 18% children). The participating clinicians classified each case as IIM or non-IIM. Generally, the classification of any given patient was based on few variables, leaving remaining variables unmeasured. We investigated the strength of the association between all variables and between these and the disease status as determined by the physician. We considered three approaches: (1) a probability-score approach, (2) a sum-of-items approach criteria and (3) a classification-tree approach.

    Results The approaches yielded several candidate models that were scrutinised with respect to statistical performance and clinical relevance. The probability-score approach showed superior statistical performance and clinical practicability and was therefore preferred over the others. We developed a classification tree for subclassification of patients with IIM. A calculator for electronic devices, such as computers and smartphones, facilitates the use of the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria.

    Conclusions The new EULAR/ACR classification criteria provide a patient's probability of having IIM for use in clinical and research settings. The probability is based on a score obtained by summing the weights associated with a set of criteria items.

  • 117. Brauner, S.
    et al.
    Zhou, W.
    Backlin, Carin
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Green, T. M.
    Folkersen, L.
    Ivanchenko, M.
    Lofstrom, B.
    Xu-Monette, Z. Y.
    Young, K. H.
    Pedersen, L. Moller
    Moller, M. Boe
    Sundström, C.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Enblad, G.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för radiologi, onkologi och strålningsvetenskap, Enheten för onkologi.
    Baecklund, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Wahren-Herlenius, M.
    Reduced expression of TRIM21/Ro52 predicts poor prognosis in diffuse large B-cell lymphoma patients with and without rheumatic disease2015Ingår i: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 278, nr 3, s. 323-332Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ObjectiveTRIM21 (also known as Ro52) is an autoantigen in rheumatic disease and is predominantly expressed in leucocytes. Overexpression is associated with decreased proliferation, and the TRIM21 gene maps to a tumour suppressor locus. We therefore investigated the expression of TRIM21 in patients with diffuse large B-cell lymphoma (DLBCL) and its potential usefulness as a prognostic biomarker. Materials and methodsTRIM21 expression levels were assessed by immunohistochemistry in lymphoma biopsies from three cohorts of patients with DLBCL: 42 patients with rheumatic disease treated with a cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP)-like regimen, 76 CHOP-treated and 196 rituximab-CHOP-treated nonrheumatic patients. Expression was correlated with clinical and biomedical parameters. TRIM21 expression was assessed in relation to lymphocyte proliferation by quantitative PCR and correlated with H-3-thymidine incorporation and propidium iodine staining. ResultsTRIM21 expression levels differed in the lymphomas compared to normal lymphoid tissue, with reduced expression correlating with shorter overall survival in all three cohorts. In the two larger cohorts, progression-free survival was assessed and was also found to correlate with TRIM21 expression. The association was independent of commonly used clinical prognostic scores, lymphoma subtype and several previously reported prognostic biomarkers. In agreement with this clinical observation, we noted an inverse correlation between TRIM21 expression and proliferation of leucocytes invitro. ConclusionsWe show that loss of TRIM21 expression is associated with more aggressive lymphoma and increased proliferation, whereas maintenance of TRIM21 expression is associated with better prognosis in patients with DLBCL. Based on our findings, we suggest that TRIM21 should be considered as a novel biomarker for lymphoma characterization and for predicting patient survival.

  • 118.
    Brauner, Susanna
    et al.
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Folkersen, Lasse
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Kvarnstrom, Marika
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Meisgen, Sabrina
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Petersen, Sven
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Franzen-Malmros, Michaela
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Mofors, Johannes
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Brokstad, Karl A.
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway..
    Klareskog, Lars
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Jonsson, Roland
    Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway..
    Westerberg, Lisa S.
    Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden..
    Trollmo, Christina
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Malmstrom, Vivianne
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Ambrosi, Aurelie
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    Kuchroo, Vijay K.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Nordmark, Gunnel
    Harvard Med Sch, Evergrande Ctr Immunol Dis, Boston, MA USA.;Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA..
    Wahren-Herlenius, Marie
    Karolinska Univ Hosptial, Karolinska Inst, Dept Med, Stockholm, Sweden..
    H1N1 vaccination in Sjogren's syndrome triggers polyclonal B cell activation and promotes autoantibody production2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, nr 10, s. 1755-1763Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives

    Vaccination of patients with rheumatic disease has been reported to result in lower antibody titres than in healthy individuals. However, studies primarily include patients on immunosuppressive therapy. Here, we investigated the immune response of treatment-naive patients diagnosed with primary Sjogren's syndrome (pSS) to an H1N1 influenza vaccine.

    Methods

    Patients with Sjogren's syndrome without immunomodulatory treatment and age-matched and gender-matched healthy controls were immunised with an H1N1 influenza vaccine and monitored for serological and cellular immune responses. Clinical symptoms were monitored with a standardised form. IgG class switch and plasma cell differentiation were induced in vitro in purified naive B cells of untreated and hydroxychloroquine-treated patients and healthy controls. Gene expression was assessed by NanoString technology.

    Results

    Surprisingly, treatment-naive patients with Sjogren's syndrome developed higher H1N1 IgG titres of greater avidity than healthy controls on vaccination. Notably, off-target B cells were also triggered resulting in increased anti-EBV and autoantibody titres. Endosomal toll-like receptor activation of naive B cells in vitro revealed a greater propensity of patient-derived cells to differentiate into plasmablasts and higher production of class switched IgG. The amplified plasma cell differentiation and class switch could be induced in cells from healthy donors by preincubation with type 1 interferon, but was abolished in hydroxychloroquine-treated patients and after in vitro exposure of naive B cells to chloroquine.

    Conclusions

    This comprehensive analysis of the immune response in autoimmune patients to exogenous stimulation identifies a mechanistic basis for the B cell hyperactivity in Sjogren's syndrome, and suggests that caution is warranted when considering vaccination in non-treated autoimmune patients.

  • 119.
    Bremander, Ann
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Bio- och miljösystemforskning (BLESS). FoU Spenshult & Lunds universitet, Lund, Sverige.
    Reumatoid artrit2015Ingår i: Fysisk aktivitet vid reumatisk sjukdom / [ed] Christina H. Opava, Lund: Studentlitteratur AB, 2015, 1:1, s. 129-139Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [sv]

    Reumatoid artiri (RA) medför ofta konsekvenser för en persons funktionstillstånd, upplevda hälsa och livskvalitet. Att främja förmågan till fysisk aktivitet är en viktig uppgift för hälso- och sjukvården och ger stora vinster för den enskildes hälsa. Rekommendationer för om fysisk aktivitet och träning har gått från vila och passiv rörelseträning till att idag kunna jämställas med aktiv träning på samma nivå som finns i rekommendationer till befolkningen i allmänhet. Naturligtvis måste träningen anpassas till individens behov, förutsättningar och önskemål.

  • 120.
    Bremander, Ann
    et al.
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Rydberglaboratoriet för tillämpad naturvetenskap (RLAS). Lund University, Lund, Sweden & Spenshult Research and Development Center, Halmstad, Sweden.
    Forslind, K.
    Lund University, Lund and Helsingborg, Sweden & Helsingborg's hospital, Helsingborg, Sweden.
    Eberhardt, K.
    Lund University, Lund, Sweden.
    Andersson, M.
    Lund University, Lund, Sweden & Spenshult Research and Devlopment Centre, Halmstad, Sweden.
    Functional Impairment in Patients with RA in an Eight Year Perspective2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, nr Suppl. 2, s. 1513-1514Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In people with Rheumatoid arthritis (RA) impaired physical functioning is an acute as well as long term effect of the disease. Observational performance tests reflecting range of motion in upper as well as in lower extremities should be easy to perform in the clinic as well as in research as a complement to self-reported measures of physical functioning. The Signal Of Functional Impairment (SOFI)1 is a performance test which so far has been applied only in Sweden but commonly used in the clinic and in long term follow-up clinical studies.

    Objectives: The aim was to study performance-based function assessed with SOFI over 8 years and, secondly, to study which items included in SOFI that were associated with change in functioning over time.

    Methods: An inception cohort of 1 052 patients with early RA, from the BARFOT-study, recruited 1992–2006 was investigated, mean (SD) age was 54 years (14), 70% were women. The patients were followed by a structured protocol at baseline, 3 and 6 months and at 1, 2, 5, and 8 years. SOFI consists of 3 parts measuring hand, arm (upper), and leg (lower) function (1). Hand function is tested by 4 movements; cylinder grip (H1), pen grip (H2), pincer grip (H3) and opposition of the thumb (H4). Arm function is assessed by 3 movements; hand behind the head and the ability to touch the cervical spine processes with fingers (A1), elbow supination (A2) and elbow extension (A3). Leg function is tested by 4 movements; the ability to touch the opposite knee with the heel while sitting (L1), knee extension in supine position (L2), dorsiflexion of the foot standing on a balance board (L3), and the ability to stand on tip toes without shoes (L4). An assessor scores the patient's ability to perform the different tests on an ordinal scale (0=normal, 1= partly impaired and 2= unable to perform). The range of SOFI scores is 0–44 (best to worst).

    Results: At baseline the mean (SD) SOFI was 7.2 (5.8), and at 1 year follow-up the improvement was 2.75 (5.65), p<0.001. From 1 year to 8 year follow-up the deterioration was 1.5 (4.6), p<0.001. When studying hand, upper and lower function separately, the pen grip and the ability to stand on tip toes improves most during the first year. From 1 to 8 year the pincer grip and the ability to stand on tip toes are the items that deteriorate most (Figure). Assessment of the pen grip, the pincer grip and the ability to stand on tip toes explain 58% to 70% of the SOFI score over time, with the highest rate at 5 (65%) and 8 years follow-up (70%).

    Conclusions: Functioning as assessed by SOFI improved during the first year in patients with early RA and then deteriorated slowly. Over a longer period, pincer grip and the ability to stand on tip toes seemed to be the two most important items to measure when assessing functional impairment over time. © 2017, BMJ Publishing Group Limited

  • 121.
    Bremander, Ann
    et al.
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Rydberglaboratoriet för tillämpad naturvetenskap (RLAS). Department of Clinical Sciences, Section of Rheumatology, Lund, Sweden & R&D centre, Spenshult, Halmstad, Sweden.
    Haglund, Emma
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Rydberglaboratoriet för tillämpad naturvetenskap (RLAS). R&D centre, Spenshult, Halmstad, Sweden.
    Bergman, Stefan
    Department of Clinical Sciences, Section of Rheumatology, Lund, Sweden & R&D centre, Spenshult, Halmstad, Sweden & Primary Health Care Unit, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Measures of Physical Activity and Fear Avoidance in People with Chronic Pain2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr Suppl. 2, s. 1829-1830, artikel-id SAT0737-HPRArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Lifestyle factors such as physical activity (PA) has the possibility to contribute to improved health and quality of life in the population as well as in chronic diseases. Most often PA is self-reported while measures of the aerobic capacity are more seldom measured in subjects with chronic pain.

    Objectives To describe physical activity levels (self-reported and aerobic capacity) in people with chronic pain classified as regional or widespread and to compare the findings with a group that report no pain.

    Methods From the 2016 follow-up of the Swedish population based Epipain cohort (n 1321), 146 subjects were invited to a clinical assessment where the aerobic capacity was assessed by using a submaximal bicycle test, the Ekblom-Bak test, together with assessment of the Borg scale for perceived exertion (RPE). Aerobic capacity was also classified as low, average or high according to data from the general population. Self-reported physical activity was coded as MVPArec if recommended levels of PA was reported (physically active on a moderate level ≥150 min/week (MPA) or on an vigorous level ≥75 min/week (VPA) or not). The Fear Avoidance Beliefs Questionnaire for PA (FABQ-PA, 0–24 best to worst) and for work (FABQ-W, 0–48 best to worst) were also assessed. The participants were classified as having chronic widespread pain (CWP), chronic regional pain (CRP) or no chronic pain (NCP) based on a pain mannequin presenting 0–18 pain regions and if pain had lasted for 3 months or more. Chi2 and Kruskal-Wallis tests were performed to study differences between the three pain groups.

    Results 141/146 (97%) subjects (mean (SD) age 59.4 (8.2) years) whereof 61% were women, could be classified into pain groups; 43 as CWP (84% women), 43 as CRP (42% women) and 55 as NCP (58% women). The group with CWP was slightly older than those with CRP (mean (SD) age 57.0 (7.6) years vs. 61.9 (6.9) years, p 0.02). The CWP group also had lower aerobic capacity (mean (SD) 2.2 (0.5) l/min vs. 2.6 (0.6) l/min, p 0.03), and a larger proportion was classified as having low aerobic capacity (CWP 21%, CRP 7% and NCP 10%, p 0.04). The proportion of MVPArec did not differ between the groups; CWP 70%, CRP 81% and NCP 74% (p 0.5). There was neither a difference between the groups in BMI, RPE or in sitting hours/week (p>0.6). However, differences were found in the FABQ where in the PA scale those with CRP had worse scores compared with NCP (mean (SD) 11.2 (7.3) vs. 6.0 (6.0), p<0.001), the difference between CWP (mean (SD) 8.9 (6.7)) and NCP was p 0.06. In the work subscale of FABQ, CWP had worse scores compared with CRP (mean (SD) 18.9 (15.7) vs. 10.0 (12.5), p 0.002) and CRP had worse scores compared to those with NCP (mean (SD) 10.0 (12.5) vs. 6.5 (9.1), p<0.001).

    Conclusions In this sample of subjects with chronic pain or no pain, having widespread pain tended to affect the aerobic capacity negatively while self-reports of reaching recommended levels of physical activity did not differ between groups. Fear avoidance in relation to physical activity and especially in relation to work was more noticeable in subjects with chronic pain compared to those with no pain. Measures of aerobic capacity and information of fear avoidance beliefs might help health professionals to better tailor the non-pharmacological treatment for subjects with chronic pain.

    Disclosure of Interest None declared

    © 2018, Published by the BMJ Publishing Group Limited.

  • 122.
    Bremander, Ann
    et al.
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Bio- och miljösystemforskning (BLESS).
    Jacobsson, Lennart T. H.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bergman, Stefan
    Research and Development Centre Spenshult, Halmstad, Sweden.
    Haglund, Emma
    Research and Development Centre Spenshult, Halmstad, Sweden.
    Petersson, Ingemar
    Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden.
    Smoking is Associated with Worse and More Widespread Pain, Worse Fatigue, General Health and Quality of Life in a Swedish population Based Cohort of Patients with Psoriatic Arthritis2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S777-S778, artikel-id 1828Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background/Purpose: Smoking has been found to be associated with an increased risk of developing psoriatic arthritis (PsA)1. The purpose of this study was analyse possible associations of smoking habits with self-reported clinical features in a large population based cohort of patients with a diagnosis of PsA.

    Methods: All health care seeking subjects with a diagnose of PsA according to ICD 10 codes (given at least once by a rheumatologist/internist or twice by any other physician) were identified by a regional health care register during 2003-20072. In 2009 all identified subjects aged 18 years or older (n=2003) were invited to participate in a cross sectional questionnaire survey. The questionnaire included self-reported data on smoking (never smokers or ever smokers), age at disease onset, physical function (HAQ, 0-3 best to worst), pain, fatigue and global health (numerical rating scales 0-10 best to worst) health related quality of life (EQ-5D, 0-1 worst to best), and number of painful regions noted on a pain mannequin (0-16, best to worst). Linear regression analysis was performed and all data were controlled for sex and age.

    Results: Response rate was 77% whereof 369 patients (18%) declined participation and 1185 (59%) returned the questionnaire,  mean age 57.5 (SD 13.5) years and 58% were women. 1173 subjects responded to the smoking question whereof 448 (38%) were never smokers and 725 (62%) were ever smokers.

    Mean age at disease onset was 42.3 (SD 13.4) years in never smokers vs. 46.0 (SD 13.2) in ever smokers. Never smokers vs. ever smokers had mean HAQ 0.59 (SD 0.6) vs. 0.71 (SD 0.6),  mean pain 3.9 (SD 2.4) vs.4.4 (SD 2.5),  mean fatigue 4.4 (SD 2.8) vs. 5.0 (SD 2.7),  mean global health 3.9 (SD 2.4) vs. 4.4 (SD 2.3), mean EQ-5D 0.68 (SD 0.23) vs. 0.63 (SD 0.26) and mean no of painful regions were 7.2 (SD 4.0) vs. 7.9 (SD 4.3).

    The regression analysis showed that ever smokers had worse pain with age-sex adjusted parameter estimates (B) = 0.38 (95% CI 0.09 ; 0.67), worse fatigue B = 0.34 (95% CI 0.02 ; 0.66), worse global health B = 0.36 (95% CI 0.09 ; 0.64), worse EQ-5D B = -0.04 (95% CI -0.07 ; -0.01) and an increased no of painful regions B = 0.54 (95% CI 0.02 ; 1.07) compared with never smokers.

    Conclusion: In this population based PsA cohort, patients who were ever smokers reported worse clinical features compared with never smokers. Further longitudinal studies are needed to better understand cause and effect. However, smoking cessation should be recommended due to general health perspectives and also due to disease specific issues.

  • 123.
    Bremander, Ann
    et al.
    Department of Clinical Sciences, Lund, Section of Rheumatology, Lund, Sweden & R&D Centre, Spenshult, Halmstad, Sweden.
    Malm, K.
    R&D Centre, Spenshult, Halmstad, Sweden.
    Andersson, M. L.
    Department of Clinical Sciences, Lund, Section of Rheumatology, Lund, Sweden & R&D Centre, Spenshult, Halmstad, Sweden.
    Physical Activity in Established RA and Variables Associated with Physical Activity Maintenance Over a Seven Year Period2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, nr Suppl. 2, s. 188-188, artikel-id OP0280-HPRArtikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Interventions to promote a healthy lifestyle also in patients with rheumatoid arthritis (RA) have been in focus over the last years. Physical activity (PA) defined as moderate-to-vigorous physical activity (MVPA) has the possibility to reduce disease burden in RA and may contribute to improved quality of life (QoL). It is well known that a large number of patients with RA have a sedentary life style and are less active than their healthy peers. However, less information is known about the long term change of MVPA and possible associated variables.

    Objectives: To study self-reported change of MVPA over seven years in a well-defined RA cohort.

    Methods: A lifestyle questionnaire was sent twice to patients in the BARFOT cohort, in 2010 (n 1525) and in 2017 (n 1046) with a response rate of 73% and 68% respectively and 950 patients responded to both questionnaires. All patients fulfilled the ACR criteria for classification of RA and had a disease duration at inclusion (1992 to 2006) of ≤12 months. Patients were dichotomized as being active on recommended levels of MVPA (MVPArec ;physically active on a moderate level ≥150 min/week (MPA) or on an intense level ≥75 min/week (VPA)) or not (sedentary). The patients reported body mass index, smoking habits, tender (TJC) and swollen joint count (SJC, 28-joints), patient global assessment (PatGA), pain intensity (NRS) and distribution (pain mannequin), fatigue (NRS), physical function (HAQ), health related QoL (EQ5D), comorbidities and medical treatment. Possible associated variables with meeting MVPArec at both time points or not (dependent variable) was studied by using a logistic regression analysis. All variables were adjusted for age, gender and smoking habits.

    Results: Forty-one percent (n 389) of the patients met MVPArec at both occasions, and they reported better EQ5D scores compared with the sedentary group (mean 0.77 (SD 0.18) vs 0.68 (0.27). The patients who met MVPArec were younger, (mean age (SD) 5913 years vs 6213 years, p<0.001) and were to higher extent never smokers 46% vs 38%, p=0.021. There was a negative association with meeting MVPArec and being overweight (OR 0.58, 95% CI: 0.43 to 0.96) or obese (OR 0.38, 95% CI: 0.25 to 0.59), the presence of cardiovascular (OR 0.56, 95% CI: 0.41 to 0.75) and pulmonary diseases (OR 0.51, 95% CI: 0.31 to 0.85), TJC (OR 0.98, 95% CI: 0.95 to 0.995), high pain intensity (OR 0.99, 95% CI: 0.987 to 0.998), and pain distribution (OR 0.93, 95% CI: 0.90 to 0.96), worse fatigue (OR 0.99, 95% CI: 0.998 to 0.997) and a worse physical function (HAQ, OR 0.58, 95% CI: 0.45 to 0.76). Patients with higher values in QoL (EQ5D, OR 3.1, 95% CI: 1.52 to 6.2) were positively associated with meeting MVPArec. In 2010 there were no differences in medical treatment between the groups, p=0.377. In 2017 the group meeting MVPArec included a lower number of untreated patients compared to 2010 (25% vs 34%, p=0.017).

    Conclusions: Only four out of ten patients with established RA reported to maintain recommended levels of PA over a seven year period. Experiencing high quality of life seems to be important for PA maintenance together with lower levels of pain, fatigue and better physical function. Health care professionals need to take the patient perspective into account andsupport maintenance of physical activities accordingly.

    Disclosure of Interest: None declared

  • 124.
    Bremander, Ann
    et al.
    Högskolan i Halmstad, Akademin för ekonomi, teknik och naturvetenskap, Bio- och miljösystemforskning (BLESS), Biomekanik och biomedicin. Research and Development Centre, Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden.
    Petersson, Ingemar F.
    Department of Orthopedics, Clinical Sciences Lund, Lund University, Lund, Sweden.
    Haglund, Emma
    Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden.
    Bergman, Stefan
    Research and Development Centre, Spenshult Hospital for Rheumatic Diseases, Halmstad, Sweden.
    Jacobsson, Lennart T.H.
    Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
    Smoking Is Associated with Worse and More Widespread Pain, Worse Disease Activity, Function, Fatigue and Health Related Quality of Life in Patients with Axial Spondyloarthritis: Results From a Population Based Cohort2012Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 64, nr S10, s. S43-S43, artikel-id 95Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: In subjects with early axial Spondyloarthritis (SpA) smoking has recently been associated with earlier onset of disease, worse lesions of the sacroiliac joints and in later stages syndesmophyte progression. The aim was to study associations of smoking habits with self-reported information in a large population based cohort of patients with axial SpA.

    Methods: A cross-sectional questionnaire survey performed in 2009 included all health care seeking subjects aged >18 years with a diagnosis of SpA according to ICD 10 codes identified by a regional health care register (n=3711). Smoking habits were studied in patients with ankylosing spondylitis (AS, ICD M45) and in patients who fulfilled criteria for “non AS axial SpA” (without having one of AS). Criteria for non AS axial SpA were based on data from the questionnaire: pain for 3 months or more during the last 12 months together with 2 or more features out of 5 (inflammatory back pain, history of psoriasis, uveitis/tendinitis, inflammatory bowel disease or heredity). The questionnaire included data on smoking (never smokers vs. ever smokers), disease activity (BASDAI) physical function (BASFI), general health (BAS-G) all measured with numerical rating scales 0-10 (best to worst), health related quality of life (EQ-5D, 0-1 worst to best), pain, fatigue (numerical rating scales 0-10 best to worst) and number of painful regions noted on a pain mannequin (0-16 best to worst). Linear regression analysis was performed and all data were controlled for sex and age.

    Results:

    Response rate was 76% whereof 2167 (58%) returned the questionnaire and 18% declined participation in the study. 598 subjects had an AS diagnose and 572 fulfilled the criteria for non AS axial SpA.

    The AS group had a mean age of 54 (SD14) years and 35% were women. Never smokers constituted 48% of the AS group. Ever smokers had worse scores in all studied variables compared with never smokers.

    The linear regression analysis showed that ever smokers in the AS group had worse self-reported scores in BASDAI with age-sex adjusted parameter estimate (B) = 0.60 (95% CI 0.21 ; 1.00), BASFI B = 0.51 (95% CI 0.11 ; 0.91) and fatigue B = 0.51 (95% CI  0.06 ; 1.00) . There was a tendency to worse scores for ever smokers also in EQ-5D B = -0.04 (95% CI -0.09 ; 0.001)

    Mean age in the non AS axial SpA group was 55 (SD 14) years and 68% were women. Never smokers constituted 38% of this group. Also in the non AS axial SpA group the linear regression analysis showed that ever smokers had worse self-reported scores in BASDAI with age-sex adjusted parameter estimate (B) = 0.59 (95% CI 0.23 ; 0.94), BASFI B = 0.59 (95% CI 0.17 ; 1.00), pain B = 0.45 (95% CI 0.08 ; 0.82) and fatigue B = 0.43 (95% CI  0.03 ; 0.83), no of painful areas B = 0.73 (95% CI  0.06 ; 1.46) and also in EQ-5D B = -0.06 (95% CI -0.11 ; -0.002).                                                                                                                                                

    Conclusion: In a large population based axial SpA cohort, both patients with AS and non AS axial SpA who were ever smokers reported worse clinical features compared with never smokers. Further longitudinal studies are needed to better understand cause and effect. However, smoking cessation should be recommended not only due to general health perspectives but also due to disease specific issues.

    References

    1Smokers in early axial spondyloarthritis have earlier disease onset, more disease activity, inflammation and damage, and poorer function and health-related quality of life: results from the DESIR cohort. Chung HY, Machado P, van der Heijde D, D'Agostino MA, Dougados M. Ann Rheum Dis. 2012 Jun;71(6):809-16.

  • 125.
    Brink, M.
    et al.
    Umea Univ, Rheumatol, Publ Hlth & Clin Med, Umea, Sweden..
    Hansson, M.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Mathsson Alm, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Cornillet, M.
    Univ Toulouse, INSERM, U 1056, Toulouse, France..
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Skriner, K.
    Charite, Med, Berlin, Germany..
    Serre, G.
    Univ Toulouse, INSERM, U 1056, Toulouse, France..
    Holmdahl, R.
    Karolinska Inst, Med Inflammat Res, Stockholm, Sweden..
    Klareskog, L.
    Karolinska Inst, Dept Med, Rheumatol Unit, Stockholm, Sweden..
    Rantapaa-Dahlqvist, S.
    Umea Univ, Rheumatol, Publ Hlth & Clin Med, Umea, Sweden..
    Acpa Against Different Citrullinated Peptides Identify Specific Phenotypes Of Rheumatoid Arthritis2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 792-792Artikel i tidskrift (Övrigt vetenskapligt)
  • 126. Brink, M.
    et al.
    Verheul, M. K.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Holmdahl, R.
    Toes, R. E. M.
    Klareskog, L.
    Trouw, L. A.
    Dahlqvist, S. R.
    The presence of anti-carbamylated protein antibodies prior to onset of symptoms of rheumatoid arthritis (RA) is associated with radiological progression in early RA2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr S127, s. 21-22Artikel i tidskrift (Övrigt vetenskapligt)
  • 127. Brink, M.
    et al.
    Verheul, M. K.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Toes, R. E.
    Klareskog, L.
    Trouw, L. L.
    Dahlqvist, S. Rantapaa
    Anti-Carbamylated Protein Antibodies Precede the Onset of Symptoms of Rheumatoid Arthritis in A Swedish Biobank Cohort2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, nr S2, s. 397-398Artikel i tidskrift (Övrigt vetenskapligt)
  • 128.
    Brink, Mikael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Presence of immunological markers preceding the onset of rheumatoid arthritis2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Rheumatoid arthritis (RA) is a chronic inflammatory disease with an unknown aetiology characterized by joint destruction. Both genetic and environmental factors contribute to the disease development with HLA-DRB1* alleles and smoking identified as most important. The disease is characterized by the presence of autoantibodies, originally by rheumatoid factor (RF) and more recently by anti citrullinated protein/peptide antibodies (ACPA) and antibodies against carbamylated peptides (CarP). These autoantibodies are present, not only after the onset of disease, but also prior to the onset of symptoms. The development of RA is a gradual process lasting several years before the onset of any joint symptom, but when and if there is a temporal difference in the development both between and within the different antibody systems is currently unknown. B-cells produce the antibodies, and a subset of B-cells, i.e., B-regulatory (Breg) cells, produces interleukin-10, and thus have the ability to down-regulate pro-inflammatory cytokines. Whether the Breg cells are involved in the pathogenesis of RA is, as yet, unknown.

    The aim of this thesis was to increase knowledge of the pathophysiological processes in the development of RA through identification of factors involved. The analyses involved detection of autoantibodies to post-translationally modified peptides/proteins in addition to RF isotypes, cell surface markers on immune cells in asymptomatic individuals, who have an increased risk of developing RA. In a co-analysis of the registers of patients with RA attending the Department of Rheumatology, with the registers from population based screening programmes within the Biobank of Northern Sweden, blood samples collected from individuals prior to the onset of symptoms were identified, as were those from population control subjects. A cohort of pre-symptomatic individuals also donated samples at the time of receiving a diagnosis of RA. First-degree relatives (FDR) of patients with RA were also identified and included for analyses.

    The levels of ten different ACPAs, i.e., (fibrinogen (Fib) α563-583(573), Fibα580-600(591), Fibβ62-81a(72), Fibβ62-81b(74), Fibβ36-52, a-enolase (CEP-1), triple helical collagen type II (citC1III), filaggrin (Fil307-324), vimentin (Vim) 2-17, and Vim60-75) were measured using the ImmunoCAP ISAC system (Phadia/ThermoFischer, Uppsala, Sweden) in blood samples from individuals before the onset of symptoms and when diagnosed with RA in comparison with those in population based controls. In a subset of samples, the levels of anti-CarP antibodies were measured using ELISA coated with anti-CarP-FCS, as well as analysis of RF of IgM, IgG and IgA isotype using the EliA assay (Phadia, Uppsala, Sweden). Breg cells were analysed both with and without stimulation ex vivo along with other cell types using flow cytometry in samples from patients with RA, their first degree relatives (FDR) and healthy controls.

    In paper I it was shown that levels of ACPA were initially restricted to a few antibodies but disseminated over time to involve additional different antibodies. The levels of antibodies to CEP-1, Fibß36-52, and filaggrin were significantly increased. In paper II, anti-CarP antibodies were positive in 5-13% of the individuals negative for the various ACPA studied. The presence of anti-CarP antibodies was significantly related to radiological destruction of joints at baseline, at follow-up after 24 months and to the radiological progress between baseline and 24months. In paper III, the relationships between the frequencies of RF isotypes, the ten different ACPA, anti-CCP2 and anti-CarP antibodies before the onset of any symptoms and the presence of certain combinations of antibodies were associated with a very high risk of developing RA. In paper IV Breg cells from patients with RA are functionally impaired and FDR showed a similar pattern by responding less to stimulation ex vivo than cells from healthy controls.

    In conclusion, individuals who subsequently develop RA have an increased number and amount of ACPAs, anti-CarP antibodies and RF of IgM, IgG and IgA isotype, several years before symptom onset. Most of the different antibodies analysed remain associated with disease development after adjustments for each separate antibody. In FDRs, Breg cells were functionally altered in that they produce less IL-10 and consequently contribute to a more inflammation-prone status, as in their relatives with RA. These findings contribute to information about the development of RA as well as a given individual’s risk(s) of developing RA and its progression.

  • 129.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Bokarewa, Maria
    Erlandsson, Malin
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Survivin But Not Fms-Like Tyrosine Kinase Ligand Is Up-Regulated Before Onset Of Rheumatoid Arthritis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S589-S589, Meeting Abstract: 1393Artikel i tidskrift (Övrigt vetenskapligt)
  • 130.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hansson, M.
    Mathson-Alm, L.
    Cornillet, M.
    Ronnelid, J.
    Skriner, K.
    Serre, G.
    Holmdahl, R.
    Klareskog, L.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Acpa against different citrullinated peptides identify specific phenotypes of rheumatoid arthritis2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 792-792Artikel i tidskrift (Övrigt vetenskapligt)
  • 131.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hansson, M
    Mathsson-Alm, L
    Wijayatunga, Priyantha
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Verheul, M.K
    Trouw, L.A
    Holmdahl, R
    Rönnelid, J.
    Klareskog, L.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rheumatoid Factor Isotypes in Relation to Antibodies Against Citrullinated Peptides and Anti-Carbamylated Antibodies in Individuals Before the Onset of Rheumatoid Arthritis2016Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 18, artikel-id 43Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. 

    Methods: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. 

    Results: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p < 0.0001). In samples collected >= 15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [a-enolase (CEP-1/Eno(5-21))], fibrinogen (Fib)beta(36-52), Fiba(580-600), filaggrin (CCP-1/Fil(307-324)) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p < 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. 

    Conclusions: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies.

  • 132.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hansson, Monika
    Mathsson, Linda
    Jakobsson, Per-Johan
    Holmdahl, Rikard
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stenlund, Hans
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Rönnelid, Johan
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Multiplex analyses of antibodies against citrullinated peptides in individuals prior to development of rheumatoid arthritis2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr 4, s. 899-910Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: The presence of antibodies against cyclic citrullinated peptides has been demonstrated to precede the symptom onset of rheumatoid arthritis (RA) by several years. Antibodies against 10 citrullinated autoantigen-derived peptides were analysed for reactivity before onset of symptoms. METHODS: In the Medical Biobank of Northern Sweden 409 individuals were identified, of whom 386 provided 717 samples, obtained before onset of symptoms of RA (median time 7.4 (IQR 9.3) years); 1305 population based controls were also identified. Antibodies to 10 citrullinated peptides; fibrinogen (Fib) Fibα573, Fibα591, Fibß36-52, Fibß72, Fibß74, α-enolase (CEP-1), Type II Collagen citC1(III) , filaggrin, vimentin (Vim)2-17, and Vim60-75 were analysed using a microarray system. RESULTS: The antibody fluorescence intensity of Fibß36-52, Fibß74, CEP-1, citC1(III) , and filaggrin was significantly increased in pre-disease individuals compared with controls (p<0.001). The levels of the earliest detectable antibodies (Fibα591 and Vim60-75) fluctuated over time, with only a slight increase after onset of disease. Antibodies against Fibß36-52, CEP-1 and filaggrin increased gradually reaching the highest levels of all antibodies before symptom onset. A cluster of antibodies, citC1(III) , Fibα573 and Fibß74 increased only slightly before onset of symptoms but prominently after disease onset. The odds ratio for development of RA with a combination of CEP-1 and Fibß36-52 antibodies (<3.35 years pre-dating) was 38.8 (CI95%14.5-103.5) compared with having either. CONCLUSION: Development of an immune response towards citrullinated peptides is initially restricted but expands with time to induce a more specific response with increasing levels towards onset of symptoms, particularly invoving antibodies against CEP-1, Fibß36-52 and filaggrin.

  • 133. Brink, Mikael
    et al.
    Hansson, Monika
    Mathsson-Alm, Linda
    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.
    Klareskog, Lars
    Rantapaa-Dahlqvist, Solbritt
    Rheumatoid Factor Isotypes in Relation to Antibodies Against Citrullinated Peptides in Individuals before Onset of Rheumatoid Arthritis2014Ingår i: Arthritis & Rheumatology, ISSN 2326-5191, Vol. 66, nr S10, s. S191-S191, artikel-id 447Artikel i tidskrift (Övrigt vetenskapligt)
  • 134.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hansson, Monika
    Ronnelid, Johan
    Klareskog, Lars
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, nr 7Artikel i tidskrift (Refereegranskat)
  • 135. Brink, Mikael
    et al.
    Hansson, Monika
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Klareskog, Lars
    Dahlqvist, Solbritt Rantapaa
    The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Antibodies against uncitrullinated peptides seem to occur prior to the antibodies to the corresponding citrullinated peptides2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, nr 7Artikel i tidskrift (Refereegranskat)
  • 136.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Johansson, L.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Nygren, E.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Arlestig, L.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Vitamin D in individuals before onset of rheumatoid arthritis: relation to vitamin D binding protein and its associated genetic variants2018Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 47, s. 23-24Artikel i tidskrift (Övrigt vetenskapligt)
  • 137.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Johansson, L.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Nygren, E.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, L.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Hultdin, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Vitamin d in individuals before onset of rheumatoid arthritis: relation to vitamin d binding protein and its associated genetic variants2018Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 77, s. 282-282Artikel i tidskrift (Övrigt vetenskapligt)
  • 138.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt M.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    B-Regulatory-, CD19(+)CD20(+) CD24(high)CD38(high) -Cells Are Functionally Impaired In Patients With Rheumatoid Arthritis and Healthy First Degree Relatives Compared With Controls2013Ingår i: Arthritis and Rheumatism, ISSN 0004-3591, E-ISSN 1529-0131, Vol. 65, nr Special issue, Supplement 10, s. S393-S394, Meeting Abstract: 917Artikel i tidskrift (Övrigt vetenskapligt)
  • 139. Brink, Mikael
    et al.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Hansson, Monika
    Mathsson, Linda
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Serre, Guy
    Jakobsson, Per-Johan
    Holmdahl, Rikard
    Klareskog, Lars
    Dahlqvist, Solbritt Rantapaa
    Antibodies against native collagen and citrullinated proteins precede the development of rheumatoid arthritis with a consecutive pattern2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, s. A22-A22Artikel i tidskrift (Övrigt vetenskapligt)
  • 140.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Verheul, M. K.
    Ronnelid, J.
    Holmdahl, R.
    Toes, R. E. M.
    Klareskog, L.
    Trouw, L. A.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    The presence of anti-carbamylated protein antibodies prior to onset of symptoms of rheumatoid arthritis (RA) is associated with radiological progression in early RA2014Ingår i: Scandinavian Journal of Rheumatology, ISSN 0300-9742, E-ISSN 1502-7732, Vol. 43, nr Suppl. 127, Meeting Abstract: PP109, s. 21-22Artikel i tidskrift (Övrigt vetenskapligt)
  • 141.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Verheul, M. K.
    Ronnelid, J.
    Toes, R. E.
    Klareskog, L.
    Trouw, L. L.
    Rantapää Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Anti-carbamylated protein antibodies precede the onset of symptoms of rheumatoid arthritis in a Swedish biobank cohort2014Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 73, s. 397-398Artikel i tidskrift (Övrigt vetenskapligt)
  • 142. Brink, Mikael
    et al.
    Verheul, Marije K.
    Rönnelid, Johan
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Klinisk immunologi.
    Berglin, Ewa
    Holmdahl, Rikard
    Toes, Rene E. M.
    Klareskog, Lars
    Trouw, Leendert A.
    Rantapaa-Dahlqvist, Solbritt
    Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage2015Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, artikel-id 25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P < 0.001) and also increased significantly after disease onset (P < 0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P < 0.05, all). Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.

  • 143.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Verheul, Marije K.
    Rönnelid, Johan
    Berglin, Ewa
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Holmdahl, Rikard
    Toes, Rene E. M.
    Klareskog, Lars
    Trouw, Leendert A.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Anti-carbamylated protein antibodies in the pre-symptomatic phase of rheumatoid arthritis, their relationship with multiple anti-citrulline peptide antibodies and association with radiological damage2015Ingår i: Arthritis Research & Therapy, ISSN 1478-6354, E-ISSN 1478-6362, Vol. 17, artikel-id 25Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The presence of a new autoantibody system, anti-carbamylated protein (anti-CarP) antibodies, has been identified in rheumatoid arthritis (RA). The presence of anti-CarP antibodies was evaluated in samples taken from individuals who subsequently developed RA before and after onset of symptoms and related to previously analysed antibodies against citrullinated peptides (ACPA specificities) and anti-CCP2. Methods: A total of 252 individuals, with 423 samples from before onset of symptoms of RA, and 197 population controls were identified as donors to the Medical Biobank of Northern Sweden; 192 of them were also sampled at the time of diagnosis. All samples were analysed for anti-CarP IgG and anti-CCP2 antibodies using ELISAs. Ten different antibody reactivities against citrullinated antigens (ACPA specificities) were analysed using a custom-made microarray based on the ImmunoCAP ISAC system (Phadia). Results: The concentration of anti-CarP antibodies was significantly increased in the pre-symptomatic individuals compared with controls (P < 0.001) and also increased significantly after disease onset (P < 0.001). The sensitivity for anti-CarP antibodies in the pre-symptomatic individuals was 13.9% (95% CI: 11 to 17.6) and 42.2% (95% CI: 35.4 to 49.3) following development of RA. Anti-CarP antibody positivity was found in 5.1% to 13.3% of individuals negative for anti-CCP2 or ACPA specificities. Presence of anti-CarP antibodies was significantly related to radiological destruction at baseline, at 24 months and also to radiological change (P < 0.05, all). Conclusions: The results indicate that anti-CarP antibodies are associated with disease development, even after adjusting for the presence of different ACPA fine specificities, and in anti-CCP2 negative individuals and contribute to the identification of a subset of patients with worse radiological progression of the disease independent of ACPA.

  • 144.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lejon, K
    B-regulatory cells are functionally impaired in patients with rheumatoid arthritis and in their first degree relativesArtikel i tidskrift (Övrigt vetenskapligt)
  • 145.
    Brink, Mikael
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Ärlestig, Lisbeth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Lejon, Kristina
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Immunologi/immunkemi.
    B Regulatory Cells are Functionally Impaired in Patients with Rheumatoid Arthritis and in Their First-Degree Relatives Compared with Controls2014Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 79, nr 6, s. 450-450Artikel i tidskrift (Övrigt vetenskapligt)
  • 146.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Barcelona, Spain.;Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey..
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J-E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A. A.
    UMC, Utrecht, Netherlands..
    Park, S-H
    Kvarnstrom, M.
    Karolinska Inst, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Alunno, A.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hosp Valle De Hebron, Barcelona, Spain..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Suzuki, Y.
    Univ Kanazawa, Kanazawa, Ishikawa, Japan..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Wiland, P.
    Med Hosp, Wroclaw, Poland..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    UFES, Vitoria, Spain..
    Giacomelli, R.
    Univ Aquila, Laquila, Italy..
    Seror, R.
    Univ Sud, Paris, France..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombardieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Minniti, A.
    Sapienza Univ, Rome, Italy..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Baseline Essdai/ Das Scores In 8061 Patients With Primary Sjögren Syndrome: Characterization Of Systemic Disease2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 464-465Artikel i tidskrift (Övrigt vetenskapligt)
  • 147.
    Brito-Zeron, P.
    et al.
    Hosp CIMA Sanitas, Barcelona, Spain.;Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey..
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J-E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A. A.
    UMC, Utrecht, Netherlands..
    Park, S-H
    Kvarnstrom, M.
    Karolinska Instit, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hasp Vall Hebron, Barcelona, Spain..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Suzuki, Y.
    Univ Kanazawa, Kanazawa, Ishikawa, Japan..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Sebastian, A.
    Med Hosp, Wroclaw, Poland..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    Univ Fed Espirito Santo, Vitoria, Brazil..
    Giacomelli, R.
    Univ Nagasaki, Nagasaki, Japan.;Univ Aquila, Laquila, Italy..
    Seror, R.
    Univ Paris Sud, Paris, France..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombaidieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ Hasp, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Paris Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Predicting Survival In 6240 Patients With Primary Sjögren' Syndrome (Big Data Sjögren Project)2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 311-311Artikel i tidskrift (Övrigt vetenskapligt)
  • 148.
    Brito-Zeron, P.
    et al.
    Hosp Clínic, Barcelona, Spain.
    Acar-Denizli, N.
    Msgsu, Istanbul, Turkey.
    Zeher, M.
    Univ Debrecen, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Univ Paris Sud, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Anhui, Peoples R China..
    Baldini, C.
    Univ Pisa, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    CMC, Vellore, Tamil Nadu, India..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Quartuccio, L.
    Santa Maria, Udine, Italy..
    Hernandez-Molina, G.
    INCMNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMC, Utrecht, Netherlands..
    Park, S. -H
    Catholic Univ Korea, Seoul, South Korea..
    Kvarnstrom, M.
    Karolinska Inst, Stockholm, Sweden..
    Praprotnik, S.
    UMCL, Ljubljana, Slovenia..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Univ Perugia, Perugia, Italy..
    Solans, R.
    Hosp Valle De Hebron, Barcelona, Spain..
    Suzuki, Y.
    Univ Hosp, Kanazawa, Ishikawa, Japan..
    Isenberg, D.
    UCL, London, England..
    Rischmueller, M.
    TQEH, Adelaide, SA, Australia..
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Fraile, G.
    Hosp Ramon & Cajal, Madrid, Spain..
    Sebastian, A.
    Med Hosp, Wroclaw, Poland..
    Vissink, A.
    Univ Groningen, Groningen, Netherlands..
    Nakamura, T.
    Univ Nagasaki, Nagasaki, Japan..
    Valim, V.
    Univ Fed Espirito Santo, Vitoria, Brazil..
    Giacomelli, R.
    Univ Aquila, Laquila, Italy..
    Devauchelle-Pensec, V.
    Univ Brest, Brest, France..
    Hofauer, B.
    TUM, Munich, Germany..
    Bombardieri, M.
    QMUL, London, England..
    Trevisani, V.
    Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Carsons, S. E.
    Sch Med SBU, Mineola, NY USA..
    Pasoto, S. G.
    Univ Sao Paulo, Sao Paulo, Brazil..
    Morel, J.
    Univ Montpellier, Montpellier, France..
    Retamozo, S.
    INICSA, Cordoba, Argentina..
    Gheita, T. A.
    Cairo Univ, Cairo, Egypt..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Mariette, X.
    Univ Paris Sud, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Analysis Of 9302 Patients From The Big Data International Primary Sjogren Syndrome Cohort: Clinical Presentation At Diagnosis Of European Vs Non-European Patients2017Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 76, s. 886-887Artikel i tidskrift (Övrigt vetenskapligt)
  • 149.
    Brito-Zeron, P.
    et al.
    Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Mimar Sinan Univ, Istanbul, Turkey..
    Zeher, M.
    Debrecen Univ, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Paris Sud Univ, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Peoples R China..
    Baldini, C.
    Rheumatol Clin, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Hernandez-Molina, G.
    INNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMCU, Utrecht, Netherlands..
    Valim, V.
    Espirito Santo Univ, Vitoria, Spain..
    Kvarnstrom, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Bartoloni, E.
    Perugia Univ, Perugia, Italy..
    Praprotnik, S.
    Clin Ctr Univ, Ljubljana, Slovenia..
    Isenberg, D.
    UCL, London, England..
    Solans, R.
    Vall Hebron Hosp, Barcelona, Spain..
    Rischmueller, M.
    Queen Elizabeth Hosp, Woodville, SA, Australia..
    Kwok, S. -K
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Suzuki, Y.
    Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Giacomelli, R.
    Laquila Univ, Laquila, Italy..
    Devauchelle-Pensec, V.
    Brest Univ Hosp, Brest, France..
    Bombardieri, M.
    QMUL, London, England..
    Hofauer, B.
    Rechts Isar Hosp, Munich, Germany..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands.;Haukeland Hosp, Bergen, Norway..
    Hammenfors, D.
    Fraile, G.
    Ramon Cajal Hosp, Madrid, Spain..
    Carsons, S.
    SUNY Stony Brook, Mineola, NY USA..
    Gheita, T.
    Cairo Univ, Cairo, Egypt..
    Morel, J.
    Montpellier Hosp, Montpellier, France..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Retamozo, S.
    Privado Hosp, Cordoba, Argentina..
    Horvath, I. -F
    Sivils, K.
    OMRF, Oklahoma City, OK USA..
    Theander, E.
    Lund Univ, Malmo, Sweden..
    Sandhya, P.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    De Vita, S.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Sanchez-Guerrero, J.
    INNSZ, Mexico City, DF, Mexico..
    van der Heijden, E.
    UMCU, Utrecht, Netherlands..
    Moca-Trevisano, V.
    Sao Paulo Fed Univ, Sao Paulo, Brazil..
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Mariette, X.
    Paris Sud Univ, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Worldwide Heterogeneous Diagnostic Approach To Primary Sjögren Syndrome in 8315 Patients (EULAR-SS Task Force Big Data Sjögren Project)2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 314-315Artikel i tidskrift (Övrigt vetenskapligt)
  • 150.
    Brito-Zeron, P.
    et al.
    Hosp Clin Barcelona, Barcelona, Spain..
    Acar-Denizli, N.
    Mimar Sinan Univ, Istanbul, Turkey..
    Zeher, M.
    Debrecen Univ, Debrecen, Hungary..
    Rasmussen, A.
    OMRF, Oklahoma City, OK USA..
    Seror, R.
    Paris Sud Univ, Paris, France..
    Mandl, T.
    Lund Univ, Malmo, Sweden..
    Li, X.
    Anhui Hosp, Hefei, Peoples R China..
    Baldini, C.
    Rheumatol Clin, Pisa, Italy..
    Gottenberg, J. -E
    Danda, D.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    Quartuccio, L.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Priori, R.
    Sapienza Univ, Rome, Italy..
    Hernandez-Molina, G.
    INNSZ, Mexico City, DF, Mexico..
    Kruize, A.
    UMCU, Utrecht, Netherlands..
    Valim, V.
    Espirito Santo Univ, Vitoria, Brazil..
    Kvarnstrom, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Sene, D.
    Lariboisiere Hosp, Paris, France..
    Gerli, R.
    Perugia Univ, Perugia, Italy..
    Praprotnik, S.
    Clin Ctr Univ, Ljubljana, Slovenia..
    Isenberg, D.
    UCL, London, England..
    Solans, R.
    Vall Hebron Hosp, Barcelona, Spain..
    Rischmueller, M.
    Queen Elizabeth Hosp, Woodville, SA, Australia..
    Park, S. -H
    Nordmark, Gunnel
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Reumatologi.
    Suzuki, Y.
    Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Giacomelli, R.
    LAquila Univ, Laquila, Italy..
    Saraux, A.
    Brest Univ Hosp, Brest, France..
    Bombardieri, M.
    QMUL, London, England..
    Hofauer, B.
    Rechts Isar Hosp, Munich, Germany..
    Bootsma, H.
    Univ Groningen, Groningen, Netherlands..
    Hammenfors, D.
    Haukeland Hosp, Bergen, Norway..
    Fraile, G.
    Ramon Cajal Hosp, Madrid, Spain..
    Carsons, S.
    SUNY Stony Brook, Mineola, NY USA..
    Gheita, T.
    Cairo Univ, Cairo, Egypt..
    Morel, J.
    Montpellier Hosp, Montpellier, France..
    Vollenveider, C.
    German Hosp, Buenos Aires, DF, Argentina..
    Atzeni, F.
    L Sacco Univ, Milan, Italy..
    Retamozo, S.
    Privado Hosp, Cordoba, Argentina..
    Horvath, I. -F
    Sivils, K.
    OMRF, Oklahoma City, OK USA..
    Theander, E.
    Lund Univ, Malmo, Sweden..
    Sandhya, P.
    Christian Med Coll & Hosp, Vellore, Tamil Nadu, India..
    De Vita, S.
    Santa Maria Misericordia Hosp, Udine, Italy..
    Sanchez-Guerrero, J.
    INNSZ, Mexico City, DF, Mexico..
    van der Heijden, E.
    UMCU, Utrecht, Netherlands..
    Moca-Trevisano, V.
    Sao Paulo Fed Univ, Sao Paulo, Brazil..
    Wahren-Herlenius, M.
    Karolinska Univ Hosp, Stockholm, Sweden..
    Mariette, X.
    Paris Sud Univ, Paris, France..
    Ramos-Casals, M.
    Hosp Clin Barcelona, Barcelona, Spain..
    Ethnic Differences Strongly Influence The Phenotypic Expression of Primary Sjögren: Study of 7887 Patients from 20 Countries on 5 Continents (EULAR-SS Task Force Big Data Sjögren Project)2016Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 75, s. 772-772Artikel i tidskrift (Övrigt vetenskapligt)
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