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Thromb Haemost 2013; 110(06): 1250-1258
DOI: 10.1160/TH13-04-0354
Platelets and Blood Cells
Schattauer GmbH

Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia

Conglei Li
1   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
,
Pingguo Chen
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
3   Canadian Blood Services, Toronto, Ontario, Canada
,
Brian Vadasz
1   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
,
Li Ma
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
,
Hui Zhou
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
,
Sean Lang
1   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
3   Canadian Blood Services, Toronto, Ontario, Canada
,
John Freedman
1   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
4   Department of Medicine, University of Toronto, Ontario, Canada
,
Heyu Ni
1   Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
2   Toronto Platelet Immunobiology Group, and Department of Laboratory Medicine, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
3   Canadian Blood Services, Toronto, Ontario, Canada
4   Department of Medicine, University of Toronto, Ontario, Canada
5   Department of Physiology, University of Toronto, Ontario, Canada
› Author Affiliations Financial support: This work was supported by Canadian Institutes of Health Research (MOP 68986 and MOP 119551); Equipment Funds from St. Michael’s Hospital, Canadian Blood Services, Canada Foundation for Innovation. Conglei Li is a recipient of the Connaught Scholarship, and Laboratory Medicine and Pathobiology Departmental Fellowships, University of Toronto; Sean Lang is a recipient of the Heart and Stroke Foundation of Canada (Ontario) Master’s Studentship Award; Brian Vadasz is a recipient of graduate student scholarship award from Li Ka Shing Knowledge Institute of St. Michael’s Hospital, and Laboratory Medicine and Pathobiology Departmental Fellowship, University of Toronto.
Further Information

Publication History

Received: 29 April 2013

Accepted after major revision: 19 August 2013

Publication Date:
30 November 2017 (online)

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Summary

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. Integrin αIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

Keywords

Alloimmune thrombocytopenia - platelets - β3 integrin - GPIbα - infection

 

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