The exposure of autoantigens by microparticles underlies the formation of potent inflammatory components: the microparticle-associated immune complexes.
Bottom Line: 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.
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.Show MeSH
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Mentions: Autoantibody/antigen binding comprises another plausible mechanism for formation of mpIC. Among the mechanisms that occur in RA SF and not in PA SF is citrullination, a process that generates neoepitopes recognized by autoantibodies present in abundance in many patients with RA (Yoshida et al, 2006). Specifically, citrullination is a posttranslational modification of peptidyl-arginine to peptidyl-citrulline by peptidyl arginine deiminase (PAD) enzymes; in RA SF, the PAD4 isoform levels are significantly elevated (Arita et al, 2004; Lundberg et al, 2005). Given that MPs are present in a milieu where citrullination is active, we hypothesized that the MP surface proteins may become citrullinated and give rise to autoantigens recognized by autoantibodies in RA patients and thereby promote mpIC formation. Using hs-FCM, we first evaluated whether platelet MPs are citrullinated in the course of RA pathogenesis. We find that, unlike platelet MPs generated in vitro and those in PA SF, the platelet MPs in RA SF contain citrullinated epitopes (Fig 5A and B), pointing to citrullination of MPs as a potential mechanism leading to recognition by autoantibodies.
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.