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Semin Thromb Hemost 2011; 37(6): 631-639
DOI: 10.1055/s-0031-1291373
© Thieme Medical Publishers

Piecing Together the Humoral and Cellular Mechanisms of Immune Thrombocytopenia

Lisa J. Toltl1 , Ishac Nazi2 , Reza Jafari2 , Donald M. Arnold1 , 3
  • 1Department of Medicine, Hamilton, Ontario, Canada
  • 2Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada
  • 3Department of Canadian Blood Services, Hamilton, Ontario, Canada
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Publikationsdatum:
18. November 2011 (online)

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Abstract

The precise mechanisms leading to platelet-targeted autoimmunity in immune thrombocytopenia (ITP) are not known. Cellular checkpoints normally regulate immunological self-reactivity during the development of B and T cells through cell deletion, receptor editing, induction of anergy, and extrinsic cellular suppression. When these checkpoints fail, tolerance to self-antigens may be lost. In this review, we summarize the various immune mechanisms contributing to the development of ITP and relate them back to the checkpoint model of autoimmunity. These mechanisms, including increased levels of lymphocyte growth factors, resistance to death signals, and loss of T-regulatory function, result in an environment permissive to the development of platelet-reactive B and T cells. The mechanisms that lead to thrombocytopenia once tolerance for platelet antigens is lost are examined, including complement-dependent and apoptotic pathways. An improved understanding of ITP pathogenesis will ultimately guide the development of better therapies.

KEYWORDS

Immune thrombocytopenia - self-tolerance - platelets - megakaryocytes - autoantibody

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Donald M ArnoldM.D.C.M. M.Sc. 

Department of Medicine, McMaster University, 1280 Main Street West

HSC 3V50, Hamilton, ON L8S 4K1 Canada

eMail: arnold@mcmaster.ca