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Autoantibody against integrin αβ contributes to thrombocytopenia by blocking the migration and adhesion of megakaryocytes
Author(s): ,
D. F. Zeng
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China. Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
,
F. Chen
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
,
S. Wang
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
Correspondence: Junping Wang, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan
,
S. L. Chen
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
,
Y. Xu
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
,
M. Q. Shen
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
,
C. H. Du
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
,
C. Wang
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
Correspondence: Junping Wang, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan
,
P. Y. Kong
Affiliations:
Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
,
T. M. Cheng
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
,
Y. P. Su
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
J. P. Wang
Affiliations:
State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, China
Correspondence: Junping Wang, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan
ISTH Academy. Wang J. Sep 4, 2018; 230972
Junping Wang
Junping  Wang

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Journal Abstract
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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 MKs’ 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‐αIIbβ3 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 MKs, 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 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‐αvβ3 antibody. In in vivo studies, we showed that injection with anti‐α antibody delayed platelet recovery in a mouse model of ITP.
Conclusions
These findings demonstrate that the autoantibody against integrin αβ 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.
Keyword(s)
adhesion, anti‐αvβ3 autoantibody, immune thrombocytopenic purpura, megakaryocytes, migration
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