IFN-γ treated monocyte/macrophage phagocytosis of red cells sensitized with IgG1 and IgG3 Anti-D containing identical immunoglobulin variable region genes

Cytokines play a major role in the immune response by activating mononuclear phagocytes. The aim of this study was to determine the effects of cytokines on Fc-gamma receptor (FcgammaR)-mediated phagocytosis of IgG1- or IgG3-sensitized red blood cells (RBCs). The results show a large variation in human monocyte phagocytosis independent of IgG subclass. The work suggests that current markers used to predict immune-mediated extravascular hemolysis (e.g. ITP or HDN), such as antibody amount/titre or immunoglobulin subclass, fail to take into account the immune environment. Of the cytokines studied, monocytes displayed a clear dose-dependant increased phagocytic response to interferon-gamma (IFN-gamma). More importantly, using anti-D with identical immunoglobulin variable region genes, but either IgG1 or IgG3 heavy chain isotopes, the change in phagocytosis can increase fourfold after cytokine treatment. Previous studies have shown an important role of FcgammaR II and III recruitment in phagocytosis and the importance of IgG subclass interactions with FcgammaR allotypic variants. There is an increased interest in effects of IFN-gamma on monocyte phagocytosis in the context of proinflammatory disease states. Future aims are directed towards identifying cytokine variants that regulate monocyte phagocytosis.