Enhanced phagocytosis of auto antibodies-opsonized blood cells by macrophages from virally infected mice. (INM3P.440)

Abstract

Abstract Autoimmune haemolytic anemia and idiopathic thrombocytopenic purpura are common immune disorders resulting from the phagocytosis of autoantibodies-opsonized blood cells. It has been reported that viral infection may be associated with autoimmune haemolytic anemia and idiopathic thrombocytopenic purpura in patients and may incriminate IgG and IgM antibody isotypes. Lactate Dehydrogenase-elevating Virus triggers the activation of immune cells although it does not induce usually any pathology in mice. Here we report that LDV infection increases the pathogenicity of IgM anti-platelet mAbs which is mediated by FcαμR. Interestingly, we show that this mechanism results from an enhanced Fc-dependent phagocytosis by macrophages rather than an increased expression of FcαμR. Our results also indicate that the pathogenicity of IgG anti-red blood cells is increased in virally infected mice. To date, three activating FcγR have been identified in mice, binding IgGs with different affinity : FcγRI, FcγRIII and FcγRIV. Since FcγRI has a high affinity for monomeric IgG2a, this receptor is poorly available for the binding of circulating-opsonized IgG2a. However we report an increased expression of each receptor by macrophages in contrast to FcamR whose expression is not regulated. Furthermore, we show the functional involment of these three receptors in the exacerbation of IgG-mediated anemia.