Polymorphisms of protein tyrosine phosphatase CD148 influence FcγRIIA-dependent platelet activation and the risk of heparin-induced thrombocytopenia. - Archive ouverte HAL Access content directly
Journal Articles Blood Year : 2012

Polymorphisms of protein tyrosine phosphatase CD148 influence FcγRIIA-dependent platelet activation and the risk of heparin-induced thrombocytopenia.

(1, 2) , (2, 1) , (3) , (2, 1) , (4) , (5) , (2, 6) , (3, 7) , (2, 1)
1
2
3
4
5
6
7

Abstract

Heparin-induced thrombocytopenia (HIT) is due primarily to IgG antibodies specific to platelet factor 4/heparin complexes (PF4/Hs) that activate platelets via FcγRIIA. CD148 is a protein tyrosine phosphatase that regulates Src kinases and collagen-induced platelet activation. Three polymorphisms affecting CD148 (Q276P, R326Q, and D872E) were studied in HIT patients and 2 control groups, with or without antibodies to PF4/Hs. Heterozygote status for CD148 276P or 326Q alleles was less frequent in HIT patients, suggesting a protective effect of these polymorphisms. Aggregation tests performed with collagen, HIT plasma, and monoclonal antibodies cross-linking FcγRIIA showed consistent hyporesponsiveness of platelets expressing the 276P/326Q alleles. In addition, platelets expressing the 276P/326Q alleles exhibited a greater sensitivity to the Src family kinases inhibitor dasatinib in response to collagen or ALB6 cross-linking FcγRIIA receptors. Moreover, the activatory phosphorylation of Src family kinases was considerably delayed as well as the phosphorylation of Linker for activation of T cells and phospholipase Cγ2, 2 major signaling proteins downstream from FcγRIIA. In conclusion, this study shows that CD148 polymorphisms affect platelet activation and probably exert a protec-tive effect on the risk of HIT in patients with antibodies to PF4/Hs.

Dates and versions

inserm-00726838 , version 1 (31-08-2012)

Identifiers

Cite

Jérôme Rollin, Claire Pouplard, Marie-Pierre Gratacap, Dorothée Leroux, Marc-Antoine May, et al.. Polymorphisms of protein tyrosine phosphatase CD148 influence FcγRIIA-dependent platelet activation and the risk of heparin-induced thrombocytopenia.. Blood, 2012, 120 (6), pp.1309-16. ⟨10.1182/blood-2012-04-424044⟩. ⟨inserm-00726838⟩
199 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More