Effect of major histocompatibility complex haplotype matching by C4 and MICA genotyping on acute graft versus host disease in unrelated hematopoietic stem cell transplantation

We explored whether matching of human leukocyte antigen (HLA) haplotypes between the recipient and donor of hematopoietic stem cell transplantation (HSCT) predicted by C4 and MICA typing is associated with the incidence of acute graft versus host disease (aGVHD). DNA preparations collected from a total of 81 recipient and donor pairs were used for PCR-based C4 subtyping and/or MICA sequence-based typing. Incidences of aGVHD were compared according to C4 and MICA matching. The six most common MICA alleles were MICA*008:01, *010:01, *002:01, *004, *009:01/049, and *012:01. Among the 59 unrelated pairs, HLA alleles were matched in 34 (57.6%). C4 subtypes were identical between the recipient and donor in 28 (82.4%) HLA-matched unrelated pairs, while MICA genotypes were matched in all HLA-matched unrelated pairs. In the 22 HLA-matched related pairs, all recipients showed identical C4 subtypes with their respective donors. In multivariate analysis, C4 mismatch was a significant risk factor associated with the development of aGVHD in unrelated HSCT (hazard ratio = 3.24, P = 0.006). PCR-based C4 subtyping is a simple method for assessing the genetic identity of the HLA region between a recipient and unrelated donor. This test would be also useful for prediction of aGVHD in HSCT.