The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes
Article first published online: 11 DEC 2012
Copyright © 2013 EMBO Molecular Medicine
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 5, Issue 2, pages 235–249, February 2013
How to Cite
Cloutier, N., Tan, S., Boudreau, L. H., Cramb, C., Subbaiah, R., Lahey, L., Albert, A., Shnayder, R., Gobezie, R., Nigrovic, P. A., Farndale, R. W., Robinson, W. H., Brisson, A., Lee, D. M. and Boilard, E. (2013), The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes. EMBO Mol Med, 5: 235–249. doi: 10.1002/emmm.201201846
- Issue published online: 4 FEB 2013
- Article first published online: 11 DEC 2012
- Accepted manuscript online: 19 NOV 2012 06:30AM EST
- Manuscript Accepted: 5 NOV 2012
- Manuscript Revised: 17 OCT 2012
- Manuscript Received: 8 AUG 2012
- immune complexes;
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 extracellular vesicles termed microparticles (MP) are present in the synovial fluid from patients affected with autoimmune arthritis. We examined MPs in rheumatoid arthritis (RA) using high sensitivity flow cytometry and electron microscopy. We find that the MPs in RA synovial fluid are highly heterogeneous in size. The observed larger MPs were in fact MP-containing ICs (mpICs) and account for the majority of the detectable ICs. These mpICs frequently express the integrin CD41, consistent with platelet origin. Despite expression of the Fc receptor FcγRIIa by platelet-derived MPs, we find that the mpICs form independently of this receptor. Rather, mpICs display autoantigens vimentin and fibrinogen, and recognition of these targets by anti-citrullinated peptide antibodies contributes to the production of mpICs. Functionally, platelet mpICs are highly pro-inflammatory, eliciting leukotriene production by neutrophils. Taken together, our data suggest a unique role for platelet MPs as autoantigen-expressing elements capable of perpetuating formation of inflammatory ICs.