Cloutier, N, Tan, S, Boudreau, LH, Cramb, C, Subbaiah, R, Lahey, L, Albert, A, Shnayder, R, Gobezie, R, Nigrovic, PA, Farndale, RW, Robinson, WH, Brisson, A, Lee, DM and Boilard, E (2013) The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: The microparticle-associated immune complexes. EMBO Molecular Medicine. pp. 235-249.

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 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 FcRIIa 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. In rheumatoid arthritis, immunocomplexes are commonly described as immunoglobulin-, antigen- and complement-containing structures. The authors establish that ICs can also be composed of microparticles, which form pro-inflammatory complexes. 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO

Item Type:	Article
Additional Information:	pubid: 218 nvp_institute: NIBR contributor_address: (Cloutier, Boudreau, Albert, Boilard) Faculte de Medecine de l'Universite Laval, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Quebec, Quebec, QC, Canada (Tan, Brisson) Molecular Imaging and NanoBioTechnology, IECB, UMR-CBMN University Bordeaux-1, Pessac, France (Cramb, Lahey, Robinson) Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, United States (Subbaiah) Department of Orthopaedics, Case Western Reserve University, School of Medicine, Cleveland, OH, United States (Shnayder, Nigrovic, Lee) Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States (Gobezie) The Cleveland Shoulder Institute, University Hospitals of Cleveland, Cleveland, OH, United States (Nigrovic) Division of Immunology, Boston Children's Hospital, Harvard Medical School, Boston, MA, United States (Farndale) Department of Biochemistry, University of Cambridge, Downing Site, Cambridge, United Kingdom (Lee) Novartis Institutes for Biomedical Research, Basel, Switzerland
Date Deposited:	13 Oct 2015 13:12
Last Modified:	13 Oct 2015 13:12
URI:	https://oak.novartis.com/id/eprint/22033