The Centenary of Immune Thrombocytopenia - Part 1: Revising Nomenclature and Pathogenesis

Abstract

The natural history of the immune thrombocytopenia (ITP) is interesting and intriguing because it traces different steps underlying autoimmune diseases. The review points out the main steps that have accompanied the stages of its history and the consequential changes related to its terminology. ITP is an autoimmune disease resulting from platelet antibody-mediated destruction and impaired megakaryocyte and platelet production. However, research advances highlight that a complex dysregulation of the immune system is involved in the pathogenesis of this condition. The review examines the role of the multiple immune components involved in the autoimmunity process, focusing on the more recent mechanisms, which could be new promising therapeutic targets for ITP patients.

Keywords: autoimmune disease; immune thrombocytopenia; megakaryocytopoiesis; pathogenesis; platelets.

Figure 1

Old and new definition of the different stages of disease (immune thrombocytopenia).

Figure 2

Picture of interplay of contributing factors in ITP. The triggering event for ITP is substantially unknown. Genetic factors may play an important role in the development of the disease, being associated with increased susceptibility to infections or predisposition to autoimmune diseases. The generalized immune dysregulation, with an imbalance between the immunoregulatory elements (cells, receptors, cytokines, and other signaling molecules), regulatory and effector T cells, drives pathogenic T and B cell effector responses against platelets and megakaryocytes.

Figure 3

Pathogenic loop in immune thrombocytopenia. Schematic picture of a continuous pathogenic loop carried out by APC, autoreactive CD4⁺ T cells, and autoantibody-producing B cells that maintains antiplatelet antibody production in ITP patients. A defect in the immune regulatory compartment (DCs, Tregs, Bregs) did not suppress the interaction between APC and autoreactive CD4⁺ T cells, resulting in prevention from a trigger of the pathogenic loop. APC, antigen presenting cell; GP, glycoprotein.

Figure 4

Schematic cell imbalance in ITP. Dysregulation of T cell activity and cytokine abnormalities are critical for ITP development. The unbalanced type 1/type 2 ratio leads to autoreactive B cell differentiation. Reduced number and/or impaired function of Tregs, Bregs, and tolerogenic DCs may contribute to enhance the immune activation. Bregs, B regulatory cells; pDCs, plasmacytoid dendritic cells; Tregs, T regulatory cells; Th, T helper cells; Tc, T cytotoxic cells.