Utility of DRB1 subtyping: a case report

The purpose of presenting this case is to illustrate the importance of high-resolution DNA Class 2 typing when assignment of MHC antigens is of extreme importance (i.e. bone marrow transplantation); suggest this test as a substitute for the mixed lymphocyte culture (MLC), and provide evidence that DRB1 subtype mismatches may be clinically significant. Initial serological and monoclonal HLA Class 1 and low-resolution DNA-SSP Class 2 typing of a potential bone marrow transplant patient and two sisters revealed all to be HLA identical with apparent homozygosity for DRB1 x 04. High-resolution DNA-SSP Class 2 typing was then performed and revealed electrophoretic banding patterns which were not specific for any DRB1 x 04 subtype. One sister and the patient had identical patterns, while the other sister had a different pattern. Complete HLA Class 1 and high-resolution DNA-SSP Class 2 typing of the parents was performed. The mother was found to be heterozygous for Class 1 and Class 2 antigens and possess the DRB1 x 0404, 0405 subtypes. In contrast, the father was found to be homozygous for Class 1 antigens, heterozygous for Class 2 antigens and possess the DRB1 x 0404, 0407 subtypes. This led to the initial false assumption of HLA identity for the patient and her two sisters. However, assignment of haplotypes revealed one sister to be HLA identical with the patient and the other sister to be a one-haplotype five-antigen match with the patient, mismatching for one DRB1 allele. Bone-marrow transplantation was performed utilizing the latter sister, which resulted in intractable acute graft vs. host disease that resulted in the patient's demise.