title: The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes.
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 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.
authors.affiliation: Faculté de Médecine de l'Université Laval, Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, Québec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Cloutier
authors.forename: Sisareuth
authors.initials: S
authors.lastname: Tan
authors.forename: Luc H
authors.initials: LH
authors.lastname: Boudreau
authors.forename: Catriona
authors.initials: C
authors.lastname: Cramb
authors.forename: Roopashree
authors.initials: R
authors.lastname: Subbaiah
authors.forename: Lauren
authors.initials: L
authors.lastname: Lahey
authors.forename: Alexandra
authors.initials: A
authors.lastname: Albert
authors.forename: Ruslan
authors.initials: R
authors.lastname: Shnayder
authors.forename: Reuben
authors.initials: R
authors.lastname: Gobezie
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Richard W
authors.initials: RW
authors.lastname: Farndale
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Alain
authors.initials: A
authors.lastname: Brisson
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.forename: Eric
authors.initials: E
authors.lastname: Boilard
mesh_terms: D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D010316:Particle Size; D013582:Synovial Fluid / Q000737:chemistry / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D001324:Autoantigens