Platelet FcγRIIA in immunity and thrombosis: Adaptive immunothrombosis

Sepsis and autoimmune diseases remain major causes of morbidity and mortality. The last decade has seen a new appreciation of platelets in host defense, in both immunity and thrombosis. Platelets are first responders in the blood to microbes or non-microbial antigens. The role of platelets in physiologic immunity is counterbalanced by their role in pathology, for example, microvascular thrombosis. Platelets encounter microbes and antigens via both innate and adaptive immune processes; platelets also help to shape the subsequent adaptive response. FcγRIIA is a receptor for immune complexes opsonized by IgG or pentraxins, and expressed in humans by platelets, granulocytes, monocytes and macrophages. With consideration of the roles of IgG and Fc receptors, the host response to microbes and autoantigens can be called adaptive immunothrombosis. Here we review newer developments involving platelet FcγRIIA in humans and humanized mice in immunity and thrombosis, with special attention to heparin-induced thrombocytopenia, systemic lupus erythematosus, and bacterial sepsis. Human genetic diversity in platelet receptors and the utility of humanized mouse models are highlighted.