Introduction: IFNa has been largely implicated in the ethiopathogenesis of autoimmune diseases but only recently it has\r\nbeen linked to endothelial damage and accelerated atherosclerosis in autoimmunity. In addition, proinflammatory\r\nconditions are supposed to be implicated in the cardiovascular status of these patients. Since a role for IFNa in endothelial\r\ndamage and impaired Endothelial Progenitor Cell (EPC) number and function has been reported in other diseases, we aimed\r\nto evaluate the potential associations of IFNa serum levels on EPC populations and cytokine profiles in Rheumatoid Arthritis\r\n(RA) patients.\r\nMethods: pre-EPC, EPC and mature EPC (mEPC) populations were quantified by flow cytometry analyzing their differential\r\nCD34, CD133 and VEGFR2 expression in blood samples from 120 RA patients, 52 healthy controls (HC), and 83 systemic\r\nlupus erythematosus (SLE) patients as disease control. Cytokine serum levels were measured by immunoassays and clinical\r\nand immunological data, including cardiovascular (CV) events and CV risk factors, were retrospectively obtained by\r\nreviewing clinical records.\r\nResults: Long-standing, but not recent onset RA patients displayed a significant depletion of all endothelial progenitor\r\npopulations, unless high IFNa levels were present. In fact, the IFNhigh RA patient group (n = 40, 33%), showed increased EPC\r\nlevels, comparable to SLE patients. In addition, high IFNa serum levels were associated with higher disease activity (DAS28),\r\npresence of autoantibodies, higher levels of IL-1b, IL-6, IL-10 and MIP-1a, lower amounts of TGF-b, and increased mEPC/EPC\r\nratio, thus suggesting higher rates of endothelial damage and an endothelial repair failure. Finally, the relationship between\r\nhigh IFNa levels and occurrence of CV events observed in RA patients seems to support this hypothesis.\r\nConclusions: IFNa serum marker could be used to identify a group of RA patients with increased disease activity, EPC\r\nimbalance, enhanced proinflammatory profile and higher cardiovascular risk, probably due, at least in part, to an impaired\r\nendothelial repair.
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