(Auto)immunity to cartilage matrix proteins - a time bomb?

Raimund W Kinne

doi:10.1186/ar4123

Abstract

Geng and colleagues consolidate and detail the role of cartilage oligomeric matrix protein (COMP) as a (potential) autoantigen in experimental and human arthritis, a finding also supported by the detection of COMP fragments and anti-COMP antibodies in rheumatoid arthritis serum and/or synovial fluid and by synovial B-cell responses against COMP. The reactivity to COMP is yet another example of how, in addition to collagen II and the large aggregating proteoglycan, cartilage-specific proteins can induce arthritis and contribute to autoimmunity. Progression of cartilage damage and degradation in disease is believed to promote the autoimmune reaction to cartilage components. However, Geng and colleagues show that anti-COMP mAbs bind in vivo to undamaged cartilage, as previously also observed for anti-collagen II antibodies. Whether this autoimmunity also involves modifications of cartilage matrix proteins, such as citrullination, remains to be further investigated. Latent, subpathogenic (auto)immune reactions directed against cartilage matrix proteins may thus eventually contribute to the outbreak of human arthritis.

Highlights

Geng and colleagues consolidate and detail the role of cartilage oligomeric matrix protein (COMP) as a autoantigen in experimental and human arthritis, a finding supported by the detection of COMP fragments and anti-COMP antibodies in rheumatoid arthritis serum and/or synovial fluid and by synovial B-cell responses against COMP
They convincingly show that mice immunized with mouse recombinant full-length COMP or COMP fragments produce a rapid and strong IgG response to these proteins/fragments beginning on day 14
The response continues over day 35, given that onset of COMP-induced arthritis occurs on days 36 to 38 [2] and peaks on day 50

Summary

Introduction

Geng and colleagues consolidate and detail the role of cartilage oligomeric matrix protein (COMP) as a (potential) autoantigen in experimental and human arthritis, a finding supported by the detection of COMP fragments and anti-COMP antibodies in rheumatoid arthritis serum and/or synovial fluid and by synovial B-cell responses against COMP. In a previous issue of Arthritis, Research & Therapy, Geng and collaborators from the laboratory of Rikard Holmdahl expand on the topic of cartilage oligomeric matrix protein (COMP) as an autoantigen in arthritis [1].

Results

Conclusion