Domestic and foreign donor candidates result in differential probability of matching minor histocompatibility antigens – relevance of selection for hematopoietic stem cell transplantation

Mismatches between patient and donor at minor histocompatibility antigens (minor H antigens) account for most of the genetic component of histocompatibility problems in human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantations (HSCTs). There are usually more genetic differences outside the matched HLA region between unrelated donors and patients than in transplantations between related individuals. Also, foreign unrelated donors may differ from domestic donors at several loci as allele frequencies vary between populations. To unravel differences in minor H antigen matching when using unrelated donors from various registries worldwide, we genotyped 10 minor H antigen loci for 143 consecutive Finnish patients and 424 unrelated donor candidates. We observed that probability of matching specific minor H antigens was different for domestic and foreign donor candidates. HA-2 and HA-3 minor H antigens were significantly more often mismatched with Finnish donor candidates ( P  = 0.0003 for HA-2 and P = 0.004 for HA-3), whereas ACC1 and ACC2 minor H antigens were significantly more often mismatched with foreign donor candidates ( P  = 0.04 for ACC1 and P  = 0.03 for ACC2). This observation is of clinical importance when specific minor H antigens are intended to match or mismatch in the future to minimize the risk for graft- vs -host disease or to maximize the graft- vs -malignancy effect in HLA-matched HSCT from an unrelated donor.