Ann Rheum Dis

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Published Online First: 13 October 2006. doi:10.1136/ard.2006.064782
Annals of the Rheumatic Diseases 2007;66:537-541
Copyright © 2007 BMJ Publishing Group Ltd & European League Against Rheumatism

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CONCISE REPORT

High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset

Mohammed Mullazehi 1, Linda Mathsson 1, Jon Lampa 2, Johan Rönnelid 1

1 Unit of Clinical Immunology, Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala, Sweden
2 Unit of Rheumatology, Department of Medicine, Karolinska Institute, Stockholm, Sweden

Correspondence to:
Correspondence to:
Dr J Rönnelid
Unit of Clinical Immunology, Rudbeck Laboratory C5, SE-75185 Uppsala, Sweden; johan.ronnelid{at}klinimm.uu.se


ABSTRACT
Objective: To investigate whether the cytokine-inducing properties of surface-bound collagen type II (CII)-containing immune complexes (IC), which were reported earlier, have any clinical impact.

Methods: Anti-CII serology was analysed in 274 patients with early rheumatoid arthritis (RA). Patients with increased levels of anti-CII were followed serially for 1–5 years with regard to anti-CII IC-induced levels of tumour necrosis factor (TNF){alpha}, interleukin (IL)1ß and IL8. Levels of antibodies and IC-induced cytokines were compared with clinical indices over 5 years of follow-up.

Results: 5/100 healthy controls and 24/274 (8.8%) patients with RA exhibited increased levels (>29 arbitrary units (AU)/ml) of anti-native CII antibodies, a non-significant difference. 9/274 (3.3%) patients with RA and no controls comprised a discrete group with high anti-CII levels >450 AU/ml. These high anti-CII level sera were associated with induction of pro-inflammatory cytokines by anti-CII-containing IC formed in vitro. 8/9 patients with high baseline anti-CII levels exhibited a parallel decline in antibody levels, IC-induced cytokines, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Anti-CII-positive patients had significantly increased levels of CRP and ESR at baseline, but not later during the follow-up.

Conclusions: Anti-native CII-positive patients with RA have a distinct clinical phenotype characterised by an early acute phase response that might be driven by anti-CII-containing IC in joint cartilage.


Abbreviations: AU, arbitrary unit; BSA, bovine serum albumin; CII, collagen type II; CRP, C reactive protein; DAS, disease activity score; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; IC, immune complex; IL, interleukin; OD, optical density; PBMC, peripheral blood mononuclear cell; PBS, phosphate-buffered saline; RA, rheumatoid arthritis; RF, rheumatoid factor; TNF, tumour necrosis factor




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Immune Complex Pathophysiology
Ann. N.Y. Acad. Sci., August 1, 2007; 1109(1): 66 - 83.
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