PLATELET MEMBRANE GLYCOPROTEIN III (GPIII) IS KNOWN TO BE THE LOCUS FOR THE PLATELET ALLOANTIGEN PLA1.

PLATELET MEMBRANE GLYCOPROTEIN III (GPIII) IS KNOWN TO BE THE LOCUS FOR THE PLATELET ALLOANTIGEN PLA1. THIS ANTIGEN IS A GENE PRODUCT OF ONE ALLELE OF A BI-ALLELIC SYSTEM HAVING THE OBSERVED DISTRIBUTION OF: PLA1A1=0.69; PLA1A2= 0.28; AND PLA2A2=0.03. EXPOSURE TO THE PLA1 ANTIGEN CAN INDUCE ALLOIMMUNIZATION IN PLA2A2 INDIVIDUALS AFTER PLATELETTRANSFUSIONS OR DURING PREGNANCY IN PLA2A2 MOTHERS CARRYING PLA1A2 INFANTS. THIS ALLOIMMUNIZATION PRODUCES ANTI-PLA1 ANTIBODIES WHICH CAN RESULT IN SEVERE THROMBOCYTOPENIA IN BOTH POST-TRANSFUSION PURPURA OR IN IMMUNE NEONATAL THROMBO-CYTOPENIA. SINCE A LARGE FRACTION OF THE POPULATION IS PLA1A1, THEY MAY, IN A SIMILAR MANNER, DEVELOP ALLOANTI- BODIES TO THE PLA2 ANTIGEN. THIS PROCESS MAY ACCOUNT FOR PATIENTS WHO BECOME REFRACTORY TO PLATELET TRANSFUSION DURING PLATELET SUPPORT THERAPY AND WHO SHOW EVIDENCE OF PLATELET-SPECIFIC ANTIBODIES UNRELATED TO ANTI-HLA SENSITI- ZATION. THEREFORE, THERE IS A SIGNIFICANT CLINICAL USE FOR A SYSTEM WHICH CAN DETECT THE PRESENCE OF THESE SPECIFIC ANTI-PLATELET ANTIBODIES AND DETERMINE THE PHENOTYPE OF RECIPIENTS OF PLATELET TRANSFUSIONS AND OF EXPECTANT MOTHERS. A NEW, SIMPLE, SPECIFIC ASSAY TECHNIQUE FOR DETECTION OF THE ANTI-PLA1 OR -PLA2 ANTIBODIES IN PATIENT SERA HAS BEEN DEVELOPED; USING THE SAME TECHNOLOGY, AN ASSAYFOR QUANTITATION OF THESE TWO ANTIGENS ON PLATELET SURFACES TO DETERMINE THE PLATELET PLA1/A2 PHENOTYPE WAS ESTABLISHED.BOTH ASSAYS USE LABELED, PURIFIED GPIII IN A QUANTITATIVE IMMUNOPRECIPITATION ASSAY. THE PHASE I PLAN OF THIS PRO- POSAL WILL DEVELOP THIS ASSAY INTO A BIOTIN-AVIDIN LINKED SYSTEM HAVING A FORMAT COMPATIBLE WITH EXPANSION TO A COMMERCIAL KIT. PHASE II OF THE PROJECT WOULD INVOLVE DEVELOPMENT OF THIS ASSAY SYSTEM TO AN INEXPENSIVE KIT FORM AND PRODUCTION FOR USE IN CLINICAL EVALUATION.