Identification of new KLF1 and LU alleles during the resolution of Lutheran typing discrepancies.

BACKGROUND: The Lu(b) antigen is expressed on red blood cells (RBCs) of the majority of individuals in all populations. Its absence in transfused patients may lead to alloantibody production and mild-to-moderate transfusion reactions, and in pregnancies to mild hemolytic disease of the fetus and newborn. This report describes the results of discrepancy resolution between apparent LU*A/LU*B or LU*B/LU*B genotypes and apparent Lu(b-) or Lu(b+ weak) phenotypes in one Asian and 10 Caucasian blood donors. STUDY DESIGN AND METHODS: Whole blood samples were analyzed by molecular methods to resolve discrepancies between Lu(b-) phenotypes detected by serology and Lu(b+) phenotypes predicted by genotyping. RBC agglutination assays were performed with commercial and patient antisera by tube or gel column methods. Genotyping was performed on commercial arrays that target the LU*A/LU*B polymorphism at Position c.230. The discrepancies were resolved by sequencing of genomic DNA and in some cases by sequencing of cloned DNA fragments. RESULTS: Eleven new alleles with coding sequence variants were identified, seven in the KLF1 gene, which are presumed to act dominantly to silence LU expression, and four in the LU gene itself. The alleles are KLF1*114delC, KLF1*298T, KLF1*304C,484insC, KLF1*304C,1000del2, KLF1*621G, KLF1*948delC, KLF1*1040A,1045delT, LU*B(559T,711T,714T), LU*B(611A,638T), LU*B(1049del2ins3), and LU*B(1306T,1340T,1671T,1742T). CONCLUSION: Besides confirming common phenotypes and detecting rare antigen-negative phenotypes, the use of molecular methods in blood donor typing can prompt the identification of new alleles through discrepancy resolution.