Assessment of CD25/CD4 in Idiopathic Thrombocytopenic Purpura

Abstract

P rimary immune thrombocytopenia, or idiopathic thrombocytopenic purpura (ITP), is an autoimmune disorder characterized by isolated thrombocytopenia due to accelerated platelet destruction and impaired platelet production. Autoantibodies against platelet surface glycoproteins (GP), such as GPIIb/IIIa and GPIb/IX complexes, play major roles in both platelet destruction and impaired platelet production. The diagnosis of ITP is a process of exclusion. First, it has to be determined that there are no blood abnormalities other than a low platelet count, and no physical signs other than bleeding. Then, secondary causes (5–10 percent of suspected ITP cases) should be excluded. Such secondary causes include leukemia, medications (e.g., quinine, heparin), lupus erythematosus, cirrhosis, HIV, hepatitis C, congenital causes, antiphospholipid syndrome, von Willebrand factor deficiency, onyalai and others. Although corticosteroids and splenectomy remain central to the treatment of ITP, a new class of drugs, i.e., thrombopoietin receptor agonists (TPO-RAs) and rituximab, have substantially broadened the therapeutic options for refractory ITP patients. Moreover, the success of TPO-RAs in ITP patients shows that reduced platelet production caused by impaired megakaryocytopoiesis plays a greater role in ITP than previously recognized. T cell-mediated cytotoxicity and T cell functional abnormalities may also be involved in its pathogenesis of ITP beside autoantibody-independent mechanisms by B cells. Regulatory T cells characterized by CD4, CD25, and transcription factor forkhead box P3, called Tregs, constitute approximately 5%-10% of T cells and play an important role in self-tolerance. Tregs contribute to maintenance of peripheral immune tolerance, and their defects are thought to play a role in the pathogenesis of various autoimmune diseases which one of them is ITP. ITP patients had reduced frequency of Tregs in circulation, bone marrow, and spleen, and Treg function is impaired. Treg dysregulation is improved after platelet count is recovered by treatment with dexamethasone, rituximab, or thrombopoietin receptor agonists.