Autoantibody against integrin v3 contributes to thrombocytopenia by blocking the migration and adhesion of megakaryocytes

Background The pathogenesis of immune thrombocytopenia (ITP) has not been fully clarified. Anti-v3 integrin autoantibody is detected in chronic ITP patients, but its contribution to ITP is still unclear. Objectives To clarify the potential role of anti-v3 integrin autoantibody in chronic ITP and the related mechanism. Methods Relationship between levels of anti-v3 autoantibody and platelets in chronic ITP patients was evaluated. The influence of anti-v3 antibody on megakaryocyte (MK) survival, differentiation, migration and adhesion was assessed, and the associated signal pathways were investigated. Platelet recovery and MKs' distribution were observed in an ITP mouse model pretreated with different antibodies. Result In this study, we showed that the anti-v3 autoantibody usually coexists with anti-IIb3 autoantibody in chronic ITP patients, and patients with both autoantibodies have lower platelets. In invitro studies, we showed that the anti-v3 antibody had no significant effect on the survival and proliferation of MKs, whereas it decreased formations of proplatelet significantly. Anti-v3 antibody impeded stromal cell derived facor-1 alpha (SDF-1)- mediated migration and inhibited the phosphorylation of protein kinase B. Anti-v3 antibody significantly inhibited MKs' 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 MKs were pretreated with anti-v3 antibody. In invivo studies, we showed that injection with anti-(v) antibody delayed platelet recovery in a mouse model of ITP. Conclusions These findings demonstrate that the autoantibody against integrin (v3) 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.