PS2:33 Microparticles from sle patients are a source of interferon-alpha

Systemic lupus erythematosus (SLE) is the prototype of systemic autoimmune disorders. Interferon alpha is a pleiotropic cytokine that can affect multiple cell types involved in lupus. Dendritic cells (DC) have a special role in the production of IFN and are the main sources of serum interferon. IFN has the potential to dramatically influence the development, progression, and pathogenesis of SLE as it can influence the function and activation state of most major immune cell subsets and function as a bridge between innate and adaptive immunity. Circulating microparticles (MPs) are ubiquitous in the blood of healthy individuals, These MPs play an active role in coagulation and intercellular communication and assist in activation or suppression of the immune system, depending on their parental cell origin. Changes in the concentration and/or composition of circulating Mps have been described in various autoimmune diseases, including rheumatoid arthritis (RA) systemic sclerosis (SSc) and SLE. For SLE, the reported microparticle-related changes remain somewhat inconclusive. To better understand the role of MPs in SLE patients, we analysed the presence of IFN-alpha on MPs surface. MPs were isolated from citrate-treated plasma; blood cells were removed by two steps of centrifugation process (2500 g for 15 min at 20 C two time). The resulting platelet-poor-plasma (PPP), was analysed by flow cytometry with specific antibody against IFN-alpha 20 consecutive SLE patients (10 with active lupus nephritis) and 10 sex- and age-matched healthy control subjects (HC) were included in the study. We found that MPs from SLE patients carry on their surface IFN alpha. Moreover, the percentage IFNalpha +MPs was higher in SLE patients and in lupus nephritis patients than in HC, but there was not significant difference between patients with and without renal involvement. The results of the present study show for the first time the presence of IFN-alpha on MPs surface. We may assume that INF+MPs derive from DC. In lupus nephritis patients the increased recruitment of DC was at tubular interstitial level, with subsequent IFN-alpha production. Interestingly, MPs (containing RNA and DNA) could stimulate type I IFN production in plasmacytoid dendritic cells and subsequently the release of MPs from DC.