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Autoantibody against integrin α v β 3 contributes to thrombocytopenia by blocking the migration and adhesion of megakaryocytes
Author(s) -
Zeng D. F.,
Chen F.,
Wang S.,
Chen S. L.,
Xu Y.,
Shen M. Q.,
Du C. H.,
Wang C.,
Kong P. Y.,
Cheng T. M.,
Su Y. P.,
Wang J. P.
Publication year - 2018
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.14214
Subject(s) - autoantibody , pathogenesis , antibody , platelet , immunology , medicine , megakaryocyte , immune thrombocytopenia , immune system , biology , microbiology and biotechnology , haematopoiesis , stem cell
SummaryEssentials The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. We analyzed the role of anti‐αvβ3 autoantibody in the pathogenesis of ITP in patients. Anti‐αvβ3 autoantibody impeded megakaryocyte migration and adhesion to the vascular niche. Anti‐α v β 3 autoantibody potentially contributes to the pathogenesis of refractory ITP.Summary Background The pathogenesis of immune thrombocytopenia ( ITP ) has not been fully clarified. Anti‐αvβ3 integrin autoantibody is detected in chronic ITP patients, but its contribution to ITP is still unclear. Objectives To clarify the potential role of anti‐αvβ3 integrin autoantibody in chronic ITP and the related mechanism. Methods Relationship between levels of anti‐αvβ3 autoantibody and platelets in chronic ITP patients was evaluated. The influence of anti‐αvβ3 antibody on megakaryocyte ( MK ) survival, differentiation, migration and adhesion was assessed, and the associated signal pathways were investigated. Platelet recovery and MK s’ distribution were observed in an ITP mouse model pretreated with different antibodies. Result In this study, we showed that the anti‐αvβ3 autoantibody usually coexists with anti‐α II bβ3 autoantibody in chronic ITP patients, and patients with both autoantibodies have lower platelets. In in vitro studies, we showed that the anti‐αvβ3 antibody had no significant effect on the survival and proliferation of MK s, whereas it decreased formations of proplatelet significantly. Anti‐αvβ3 antibody impeded stromal cell derived facor‐1 alpha ( SDF ‐1α)‐ mediated migration and inhibited the phosphorylation of protein kinase B. Anti‐αvβ3 antibody significantly inhibited MK s’ adhesion to endothelial cells and Fibrogen. The phosphorylation of focal adhesion kinase and proto‐oncogene tyrosine‐protein kinase Src induced by adhesion was inhibited when MK s were pretreated with anti‐αvβ3 antibody. In in vivo studies, we showed that injection with anti‐α v antibody delayed platelet recovery in a mouse model of ITP . Conclusions These findings demonstrate that the autoantibody against integrin α v β 3 may aggravate thrombocytopenia in ITP patients by impeding MK migration and adhesion to the vascular niche, which provides new insights into the pathogenesis of ITP .