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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2013, Vol. 7 Issue (4) : 418-424     DOI: 10.1007/s11684-013-0297-8
REVIEW |
Advances in immunopathogenesis of adult immune thrombocytopenia
Xinguang Liu1, Yu Hou2, Jun Peng1()
1. Department of Hematology, Qilu Hospital, Shandong University, Jinan 250012, China; 2. Shandong University School of Medicine, Jinan, 250012, China
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Abstract  

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immune-mediated accelerated platelet destruction and/or suppressed platelet production. Although the development of autoantibodies against platelet glycoproteins remains central in the pathophysiology of ITP, several abnormalities involving the cellular mechanisms of immune modulation have been identified, and the pathways behind the immune-mediated destruction of platelets have opened new avenues for the design of specific immunotherapies in an attempt to reduce the platelet destruction. This review is primarily focused on the recent literature with respect to immunopathological mechanisms in patients with ITP.

Keywords primary immune thrombocytopenia      B lymphocytes      T lymphocytes      antigen-presenting cells      cytokines     
Corresponding Authors: Peng Jun,Email:junpeng88@sina.com.cn   
Issue Date: 05 December 2013
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-013-0297-8     OR     http://academic.hep.com.cn/fmd/EN/Y2013/V7/I4/418
Fig.1  Simplified representation of the pathophysiology of ITP. The primary mechanism for the loss of tolerance in ITP is still unknown. Autoantibody-mediated platelet clearance remains the central pathogenetic mechanism. IgG-coated platelets are phagocytized by macrophages through Fcγ receptors. Platelet glycoproteins are cleaved to peptides and expressed on the antigen-presenting cell (APC) surface via MHC-II molecules. A number of new or cryptic epitopes are generated by APCs through epitope spreading. The T cell receptor (TCR) of Th cells can bind the peptide-MHC complex and then signal activation that upregulates CD154 to interact with CD40 of the APC and cause additional costimulatory interaction to occur. Binding of CD28 expressed on Th cells with the CD80 molecule overexpressed on the APC membrane of ITP patients could induce an additional co-stimulatory signal. By secreting interleukin-2 and interferon-γ, the activated Th cells can promote B cell differentiation and autoantibody production. Autoantibodies may also induce suppressed megakaryocyte maturation and platelet production. Autoreactive cytotoxic T cell-mediated platelet lysis and dysmegakariocytopoiesis constitute another alternative pathway of platelet destruction and decreased production.
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