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

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.
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Blood, American Society of Hematology, 2012, 120 (6), pp.1309-16. 〈10.1182/blood-2012-04-424044〉
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http://www.hal.inserm.fr/inserm-00726838
Contributeur : Marie Francoise Simon <>
Soumis le : vendredi 31 août 2012 - 13:38:07
Dernière modification le : jeudi 4 octobre 2018 - 09:50:10

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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, American Society of Hematology, 2012, 120 (6), pp.1309-16. 〈10.1182/blood-2012-04-424044〉. 〈inserm-00726838〉

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