OLIGOTYPING OF HLA-A2, HLA-A3, AND HLA-B44 SUBTYPES - DETECTION OF SUBTYPE INCOMPATIBILITIES BETWEEN PATIENTS AND THEIR SEROLOGICALLY MATCHED UNRELATED BONE-MARROW DONORS

We have set up a simple PCR-SSO oligotyping procedure that is able to discriminate ten HLA-A2 (2 PCR/11 probes), two HLA-A3 (1 PCR/1 probe), and two HLA-B44 subtypes (1 PCR/2 probes). The frequency of these sub types has been determined in a large panel of local blood donors and l eukemic patients in combination with their unrelated potential donors. A0201 and A*0301 were the predominant subtypes (> 95%) for A2 and A3 , respectively. B4402 occurred twice as frequently as B*4403. A2 and B44 subtype mismatches were analyzed in a group of 30 patients and the ir 116 unrelated potential donors who were matched serologically (low- stringency matching: AB without splits, DR1-10). For seven patients (2 1%) at least one A2- or B44-subtype-mismatched donor was found. For tw o of these patients (7%), the subtype-mismatched donor would have been considered as compatible on the basis of high stringency matching (AB splits, DRB1 subtypes, DRB3/B5). For one patient of Mediterranean ori gin, all five donors recruited from a north European registry (matched with high stringency) appeared to be subtype incompatible (A0201/A*0 205). The rather low percentage of A2- and B4-subtype mismatches in DR B1/B3/B5 matched combinations confirms the significance of linkage dis equilibria of HLA antigens. Because unrelated donor selection is done through international registries, however, class I subtyping might be necessary when individuals originate from different geographic areas.