The intestinal flora: The key to unraveling heterogeneity in immune thrombocytopenia?

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder characterized by enhanced platelet destruction and impaired platelet production, due to a loss of immune tolerance that leads to targeting of platelets and megakaryocytes by glycoprotein-autoantibodies and/or cytotoxic T cells. There is a high degree of heterogeneity in ITP patients signified by unpredictable disease trajectories and treatment responses. Initial studies in humans have identified intestinal microbiota perturbance in ITP. Recently, gut microbial perturbance has been linked to other autoimmune diseases. Based on these findings, we hypothesize that intestinal microbiota may influence ITP pathophysiology through several mechanisms, including induction of platelet-autoantibody production, increasing complement-dependent platelet cytotoxicity, disturbing T cell homeostasis, impairing megakaryocyte function, and increasing platelet-desialylation and -clearance. The pathophysiological heterogeneity of ITP may, at least in part, be attributed to a perturbed intestinal microbiota. Therefore, a better understanding of intestinal microbiota in ITP may result in a more personalized therapeutic approach.