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Anti-type II collagen antibodies are associated with early erosions in Rheumatoid Arthritis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. (Autoimmunity)
Department of Radiology, Innsbruck Medical University, Innsbruck, Austria.
Department of Medicine, Unit of Rheumatology, Karolinska Institutet, Solna.
Department of Medicine, Unit of Rheumatology, Karolinska Institutet, Solna. (Rheumatology)
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(English)Manuscript (Other academic)
Abstract [en]

AbstractIntroduction: We have previously reported that high levels of antibodies specific for type II collagen (anti-CII) were associated with early inflamma-tion and immune complex (IC)-associated pro-inflammatory cytokine pro-duction in vitro. In contrast, antibodies specific for cyclic citrullinated pep-tides (anti-CCP) were associated with late inflammation and late erosions in the same group of RA patients. We therefore hypothesized that anti-CII are also associated with early erosions in this patient group. Patients and Methods: Two-hundred-and-fifty-six patients from an early RA cohort were included. The Larsen score was used to score 32 joints. The results were obtained at baseline and after one and two years, respectively.Results: Anti-CII antibodies were significantly associated with increased Larsen score at disease onset using a high cut-off based on biological effects of anti-CII IC-associated cytokine production in vitro. Sizeable differences between the groups were sustained at all investigated time points. A sizeable but non-significant difference at baseline between anti-CII positive and anti-CII negative patients with RA was recorded using a conventional 95th per-centile cut-off. These differences were not evident after 1 or 2 years.Conclusion: In contrary to anti-CCP, anti-CII positive patients with RA have increased joint destruction at baseline. Anti-CII thus characterizes an early inflammatory/destructive phenotype, in contrast to the late appearance of an inflammatory/destructive phenotype in anti-CCP positive RA patients.

Keyword [en]
Rheumatoid Arthritis, Type II collagen (CII), Collagen antibodies (Anti-CII), Immune complex (IC), Erosion, Larsen score, Anti-CCP, RF
National Category
Immunology in the medical area
Research subject
Clinical Immunology; Pediatrics; Orthopaedics
URN: urn:nbn:se:uu:diva-100414OAI: oai:DiVA.org:uu-100414DiVA: diva2:210270
Available from: 2009-03-31 Created: 2009-03-31 Last updated: 2010-01-14
In thesis
1. Anti-Collagen Type II Autoantibodies in an Acute Phenotype of Early Rheumatoid Arthritis
Open this publication in new window or tab >>Anti-Collagen Type II Autoantibodies in an Acute Phenotype of Early Rheumatoid Arthritis
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Rheumatoid arthritis (RA) is an autoimmune disease with systemic inflammatory features that primarily affects small peripheral joints. Type II collagen (CII), is the most abundant collagen type in joint cartilage. Antibodies against CII (anti-CII) are found in a subpopulation of RA patients. Anti-CII can form surface-bound immune complexes (IC) in inflamed joints, which might intensify joint inflammation and destruction. In this thesis I have studied the functional effects of surface-bound anti-CII–containing IC in vitro and correlated the results to clinical parameters.

Anti-CII IC induced TNF-α, IL-1β and IL-8 production from monocytes via FcγRIIa. Anti-CII levels were dichotomously distributed in RA patients where a small outlier group (3.3%) with very high anti-CII levels showed in vitro induction of pro-inflammatory cytokines by anti-CII-containing IC. These patients also had a distinct phenotype with elevated laboratory signs of inflammation and increased radiological erosions at the time of diagnosis.

In another in vitro model, co-cultured macrophages and RA synovial fibroblasts stimulated with anti-CII IC induced the production of matrix metalloproteinases (MMP)-1 and MMP-8, enzymes responsible for the initial cleavage of CII during cartilage degradation. This was mediated via production of TNF-α and IL-1β, and especially anti-CII IC-induced IL-1β sup-ported the production of MMP-1. The presence of anti-CII antibodies in patients with early synovitis was not predictive for future RA development.

In summary, I have shown how anti-CII-containing IC may explain part of the early pathogenesis and can define a distinct clinical phenotype in RA patients with high levels of anti-CII.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 74 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 444
National Category
Immunology in the medical area
Research subject
Clinical Immunology
urn:nbn:se:uu:diva-100483 (URN)978-91-554-7486-7 (ISBN)
Public defence
2009-05-13, Rudbecksalen, Rudbeck Laboratory, Dag Hammarskjöldsv. 20, Uppsala, 09:15 (English)
Available from: 2009-04-22 Created: 2009-04-01 Last updated: 2010-05-28Bibliographically approved

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