The therapeutic blockage of IL-6 with Tocilizumab (TCZ) alters PLT and the phenotype and function of monocytes in rheumatoid arthritis (RA). Platelets (PLT) bind to a significant percentage of circulating monocytes and this immunomodulatory interaction is increased in several inflammatory and autoimmune conditions. As ACPA can be detected several years before disease onset and activated platelets contribute to vascular permeability, these data implicate a possible role for ACPA-mediated activation of platelets in arthritis (onset). We now show for the first time that ACPA can mediate an FcyRIIa dependent activation of platelets. In addition, both expression of P-selectin as number of platelets correlated with DAS44, CRP levels and ACPA-status and ACPA levels. Pre-incubation of platelets with blocking antibodies directed against FcyRIIa, completely inhibited the ACPA-mediated activation. In accordance, an enhanced platelet activation was observed after incubation with ACPA(pos) plasma versus ACPA(neg) plasma. Furthermore, levels of P-selectin expression and sCD40L release correlated with high ACPA titers. Platelets isolated from healthy controls display markers of platelet activation in the presence of plasma derived from RA patients, as determined by P-selectin expression, formation of aggregates and secretion of sCD40L. Characteristics of platelets isolated from RA patients were correlated to disease activity. Platelets from healthy controls were incubated in the presence of either plasma of RA patients or age/gender matched healthy controls plasma from ACPA(neg) or ACPA(pos) patients or in the presence of plate-bound ACPA. We now set out to determine platelet phenotype in RA and studied whether this could be influenced by the presence of Anti-Citrullinated Protein Antibodies (ACPA). Although the role of platelets in rheumatoid arthritis (RA) is relatively unexplored, recent studies point towards a contribution of platelets in arthritis.
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