High-Throughput DNA Analysis for Red Blood Cell Antigens Facilitates the Transfusion Support with Antigen-Matched Blood in Sickle Cell Disease Patients.

Background: Transfusion dependent patients as those with Sickle Cell Disease (SCD) patients become alloimmunized and have the potential to form additional antibodies with such frequency that antigen-negative blood is preferred to prevent further alloimmunization. Blood group genotyping is playing a supporting role in the routine blood banks, especially for provision of antigen-matched blood for these patients. However, current techniques for genomic typing are all labor-intensive and require manual set up and analysis by gel electrophoresis. As a result, DNA microarrays are being developed for the single nucleotide polymorphisms (SNPs) detection in the blood group genes to provide a fast procedure and an automated analysis of numerous blood group polymorphisms. We evaluated the usefulness of DNA microarray to provide a means to precisely match donor blood to the antigen-negative type of SCD patients. Method: A total of 12 DNA samples from patients with SCD (homozygous for HbS) and 84 DNA samples from blood donors, were analyzed by the HEA Beadchip (Hashmi et al, 2005) containing a total of 18 SNPs (FYA/B, FY-GATA, FY265, DOA/B (nt 378, 624, 793), COA/B, LWA/B, DIA/B, SC1/SC2, M/N, S/s, LUA/B, KEL1/2, JKA/B, DO323, DO350, HgbS) in a single reaction. Results: A genotype result was obtained for all SNPs tested on 96 samples within 4 hours of the start of testing. Results obtained by Beadchip analysis in donors were used to provide antigen-matched blood for FYA/B, FY-GATA, FY265, DOA/B, M/N, S/s KEL1/2, JKA/B, for all 12 SCD patients. This technology provided a fast procedure and facilitated the transfusion support with antigen-matched blood in SCD patients allowing the reduction of alloimunization to blood group antigens. Conclusion: This high-throughput DNA analysis has the potential not only to increase the inventory of antigen-negative blood but also to facilitate the matching of RBC component to the recipient’s blood type. It also contributes to the management of transfusions in SCD patients by allowing a more accurate selection of donor units. The application of microarray technology in transfusion medicine may have a tremendous impact on further improvement of the safety of blood transfusion.