Microparticle-associated immune complexes predominate in rheumatoid arthritis synovial fluid
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Lee, David and Boilard, Eric (2012) Microparticle-associated immune complexes predominate in rheumatoid arthritis synovial fluid. EMBO molecular medicine, 4. pp. 1-15. ISSN 1757-4676
Abstract
Immunoglobulins, antigens and complement can assemble to form immune complexes (IC). ICs can be detrimental as they propagate inflammation in autoimmune diseases. Like ICs, submicron vesicles termed microparticles (MP) can be detected in the synovial fluid from patients affected with autoimmune inflammatory arthritis. In this study, we examined MPs in rheumatoid and psoriatic arthritis using high sensitivity flow cytometry and transmission electron microscopy. Compared to those in psoriatic arthritis, we found that MPs in rheumatoid arthritis synovial fluids were more abundant and that they also displayed apparent larger dimensions. The observed larger MPs were in fact MP-containing ICs (mpICs) and accounted for the majority of the detectable ICs. These mpICs frequently expressed the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcgRIIa by platelet-derived MPs, we find that the mpICs in rheumatoid arthritis synovial fluid can form independently of the immunoglobulin receptor. Rather, mpICs display surface autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs in rheumatoid arthritis. Functionally, platelet mpICs were highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data demonstrate a unique role for platelet MPs as autoantigen-expressing elements for inflammatory ICs in rheumatoid arthritis.
| Item Type: | Article |
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| Additional Information: | Can archive post-print (ie final draft post-refereeing) or publisher's version/PDF |
| Keywords: | arthritis, immune complex, microparticle, platelet |
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| Date Deposited: | 13 Oct 2015 13:14 |
| Last Modified: | 13 Oct 2015 13:14 |
| URI: | https://oak.novartis.com/id/eprint/8108 |