Recent progress in understanding the pathogenesis of immune thrombocytopenia.
OBJECTIVE
Immune thrombocytopenia (ITP) is a bleeding disorder in which both antibody and cell-mediated autoimmune responses are directed against an individual's own platelets and/or megakaryocytes, leading to either enhanced platelet destruction and/or reduced platelet production, respectively. The cause of this platelet-specific autoimmunity remains unknown, but there has been a constant stream of recent publications that suggest ITP is the result of T-cell dysregulation.


RESULTS
In the last 18 months, a rich tapestry of studies has emerged that seems to clarify some immunopathologic issues in ITP while raising new questions related to ITP pathogenesis. The current view on the immunopathogenic mechanisms associated with ITP appears to particularly concentrate on how incompetent CD4+ T-regulatory cells (Tregs) allow autoimmune effector mechanisms to proceed and cause thrombocytopenia. There is a parallel body of recent literature focusing on molecular mimicry mechanisms, B-cell abnormalities, abnormal cytokine patterns and genetic studies in ITP. Of interest, one can recognize inter-relationships between these immune dysregulations.


CONCLUSIONS
This article will discuss the literature from the past 18 months pertaining to these observations and will show that whereas many of the T-cell defects have been clarified, new questions have also come to light and more immunopathological research is warranted.
Semple
John W
JW
Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Department of Pharmacology, University of Toronto, Canadian Blood Services, Toronto, Ontario, Canada. semplej@smh.toronto.on.ca
Provan
Drew
D
Garvey
M Bernadette
MB
Freedman
John
J
D001792:Blood Platelets / Q000276:immunology / Q000473:pathology; D006801:Humans; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D013921:Thrombocytopenia / Q000276:immunology* / Q000473:pathology*