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Antibodies against cyclic citrullinated peptide (CCP) and levels of cartilage oligomeric matrix protein (COMP) in very early arthritis: relation to diagnosis and disease activity
Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Rheumatology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Rheumatology in Östergötland.
Rheumatism Foundation Hospital, Heinola, Finland.
Department of Medicine, Division of Rheumatology, Helsinki University Central Hospital, Huch, Finland.
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2004 (English)In: Scandinavian Journal of Rheumatology, ISSN 0300-9742, Vol. 33, no 3, 185-188 p.Article in journal (Refereed) Published
Abstract [en]

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

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

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

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

Place, publisher, year, edition, pages
2004. Vol. 33, no 3, 185-188 p.
Keyword [en]
anti-CCP antibodies, COMP, rheumatoid arthritis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14376DOI: 10.1080/03009740310004856OAI: oai:DiVA.org:liu-14376DiVA: diva2:23358
Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31
In thesis
1. A population-based study on early arthritis in southern Sweden: Incidence, preceding infections, diagnostic markers and economic burden
Open this publication in new window or tab >>A population-based study on early arthritis in southern Sweden: Incidence, preceding infections, diagnostic markers and economic burden
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The total annual incidence of arthritis in this prospective cross-sectional study on adults was 115/100 000. The annual incidence of rheumatoid arthritis (RA) was 24/100 000, 29/100 000 for women, and 18/100 000 for men. For reactive arthritis (ReA) the annual incidence was slightly higher, 28/100 000, and for undifferentiated arthritis 41/100 000. The annual incidence of Lyme disease and sarcoid arthritis was low. The annual incidence of arthritis in this study compares well with findings in earlier reports from both registers and case review studies. Almost 50% of the patients in the series of 71 patients with arthritis of less than 3 months’ duration had a preceding infection. Campylobacter jejuni ReA dominated the enteric ReA group. We found only a few patients with preceding Chl. trachomatis, Chl. pneumoniae, Borrelia burgdorferi or parvovirus B19 infections. The arthritis patients with a preceding infection went into remission more often than the patients without a preceding infection. The disease specificity of anti-CCP antibodies for RA was high, 96%, confirming earlier results. Anti-CCP antibodies differentiated RA from other arthritides. Several patients in the different diagnosis groups had raised serum COMP levels, indicating cartilage involvement very early in the disease, even in mild and self-limiting disease with good prognosis. The economic burden of early joint inflammation was found to be considerable already during the first few months of the arthritis irrespective of diagnosis. Surprisingly, patients with ReA generated almost as high costs as patients with RA during thefirst few months of the disease, even though most of the ReA patients had a relatively mild disease. Sick leave accounted for about 50% of the costs. The distribution of costs in the different patient groups was skewed. The median cost per patient for the group of patients with RA was US$4385, for ReA US$4085, for other types of specified arthritis US$3361, and for undifferentiated arthritis US$1482. This underlines the necessity of quick referral and therapy, not only to decrease the inflammation and prevent functional impairment, but also to decrease the costs of early arthritis.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2003. 100 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 824
Keyword
Arthritis diagnosis, arthritis economics, Biological markers blood, Extracellular matrix proteins blood, Cost of illness
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-5225 (URN)91-7373-506-X (ISBN)
Public defence
2003-11-21, Elsa Brändströmsalen, Campus US, Linköpings universitet, Linköping, 13:00 (English)
Opponent
Supervisors
Available from: 2003-12-16 Created: 2003-12-16 Last updated: 2015-08-31Bibliographically approved
2. Autoantibodies and genetic variation in rheumatoid arthritis: aspects on susceptibility and disease course
Open this publication in new window or tab >>Autoantibodies and genetic variation in rheumatoid arthritis: aspects on susceptibility and disease course
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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

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

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

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

Place, publisher, year, edition, pages
Institutionen för molekylär och klinisk medicin, 2007. 73 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 990
Keyword
Rheumatoid arthritis, autoantibodies, single-nucleotide polymorphisms, disease course
National Category
Rheumatology and Autoimmunity
Identifiers
urn:nbn:se:liu:diva-8618 (URN)978-91-85715-39-8 (ISBN)
Public defence
2007-04-20, Berzeliussalen, CampUS, Universitetssjukhuset i Linköping, Linköping, 09:00 (English)
Opponent
Supervisors
Available from: 2007-04-20 Created: 2007-04-20 Last updated: 2015-08-31

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Söderlin, MariaKastbom, AlfStrandberg, GunnarSkogh, Thomas

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Rheumatology Faculty of Health SciencesDepartment of Rheumatology in Östergötland
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