Neonatal alloimmune thrombocytopenia; prevention of the maternal immune response may decrease fetal morbidity and mortality.

Severe NAIT is present in 1:1,500 newborns and 1:12,500 newborns are reported to experience intracranial hemorrhage leading to death or severe life long disability. NAIT is in most cases (80%) caused by maternal antibodies reactive with the fetal platelet alloantigen HPA 1a. Anti-HPA 1a antibodies cross the placenta and bind to fetal platelets. Sensitized platelets are destroyed rendering the fetus thrombocytopenic and at risk for bleeding. The antibodies are well characterized, but the underlying cellula r immune response resulting in antibody formation, including HPA 1a-specific T cell responses, is not studied so far. This study follows up a large prospective study of >100,000 pregnancies, where it was shown that identification of pregnancies at risk an d simple clinical follow up, decrease morbidity and mortality in the newborns. The new study is aimed at preventing maternal immunization with HPA 1a and thereby preventing/reducing incidence of NAIT. We propose two different approaches: (1) To prevent im munization by passive administration of anti-HPA 1a antibodies to non-immunized HPA 1bb women immediately after delivery of an HPA 1a-positive fetus. Two different sources of anti-HPA 1a antibodies will be tested: polyclonal native IgG purified from poole d sera of HPA 1a-immunized women, and recombinant monoclonal antibodies constructed from antibody genes isolated from immortalized B lymphocytes from the immunized women. (2) To prevent HPA 1a immunization by inhibiting HPA 1a-specific T cell activation. The underlying cellular immune responses that lead to production of anti-HPA 1a antibodies, especially the role of T cells, will be studied. We have recently been able to clone unique HPA 1a-specific T cell lines that will allow detailed studies of immune responses associated with NAIT, and also provide new ways of measuring immunization in affected women.