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.

Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas

“…ITP is an autoimmune disease characterized by both platelet destruction and impaired megakaryocyte and platelet production . The pathogenesis of the immune dysregulation resulting in ITP is incompletely understood, and likely quite complex.…”

“…Since Harrington's seminal 1951 experiment in which the transfusion of ITP plasma into healthy people induced thrombocytopenia, ITP has been known as a humoral disease . In ITP, autoantibodies targeting platelet surface glycoproteins (GPs) lead to platelet clearance by the mononuclear phagocytic system, primarily that of the spleen . However, it is now recognized that antibody‐mediated destruction is not the sole mechanism of platelet clearance.…”

“…However, it is now recognized that antibody‐mediated destruction is not the sole mechanism of platelet clearance. T cells play a central role in platelet destruction in ITP . A proinflammatory Th1, Th17, and Th22 cytokine milieu predominates in many ITP patients that together promote macrophage function, autoreactive B‐cell development, and T‐cell cytotoxicity .…”

“…T cells play a central role in platelet destruction in ITP . A proinflammatory Th1, Th17, and Th22 cytokine milieu predominates in many ITP patients that together promote macrophage function, autoreactive B‐cell development, and T‐cell cytotoxicity . Furthermore, immune regulators that normally serve to maintain self‐tolerance, like T and B regulatory cells, are dysfunctional in ITP, allowing the autoimmune response to persist .…”

Human platelet antigens and primary immune thrombocytopenia

“…Environmental and genetic factors, such as cytokine gene polymorphisms, human leukocyte antigens (HLAs) and human platelet antigens (HPAs) seem to play a role 9, 10, 11, 12. HPAs are polymorphisms of platelet surface Gps which result in alloantigen expression, leading to alloimmunization mainly after transfusions and pregnancies 13 .…”