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

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: N/A
Agency Tracking Number: 4984
Amount: $44,000.00
Phase: Phase I
Program: SBIR
Awards Year: 1986
Solicitation Year: N/A
Solicitation Topic Code: N/A
Solicitation Number: N/A
Small Business Information
Po Box 7539, Columbia, MO, 65205
DUNS: N/A
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 MARK E SMITH
 PRINCIPAL INVESTIGATOR
 (314) 874-2481
Business Contact
Phone: () -
Research Institution
N/A
Abstract
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.

* Information listed above is at the time of submission. *

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