Rare Antigens in Neonatal Alloimmune Thrombocytopenia

Versiti Wisconsin, Inc., Milwaukee WI

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): This R21 application is in response to PA-03-171. Neonatal alloimmune thrombocytopenia (NATP), a significant cause of morbidity and mortality in newborn infants, is the result of maternal immunization against platelet-specific alloantigens inherited from the father. Early diagnosis and treatment (pre-natal or postnatal) of this condition can greatly improve the outcome. "Common" platelet antigens known to induce antibodies that cause NATP can now be typed for and the corresponding antibodies can by detected reliably by referral laboratories. However, maternal immunization against these antigens can be documented only in about one-third of cases. We have obtained preliminary evidence that an important reason for the low diagnostic yield is that many mothers are immunized against "private" (rare) platelet-specific alloantigens not previously reported or described only in single case reports. In this application, studies are proposed to facilitate early diagnosis of NATP and to enable improved pre-natal and post-natal management with these objectives: 1. Characterize the extent to which NATP is caused by maternal immunization against low frequency platelet-specific alloantigens by typing DNA from fathers of unresolved NATP cases for recognized "rare" alloantigens. 2. Define the role of previously undescribed alloantigens as immunogens in NATP utilizing archived DNA samples from the same patient population. 3. Estimate the prevalence of "rare" platelet-specific alloantigens in the normal population using high throughput, DNA-based screening methods. 4. Generate soluble recombinant platelet glycoproteins carrying "rare" platelet alloantigens to provide a tool for rapid detection and identification of antibodies in mothers who are immunized against these antigens