MISMATCHES OF MINOR HISTOCOMPATIBILITY ANTIGENS BETWEEN HLA-IDENTICALDONORS AND RECIPIENTS AND THE DEVELOPMENT OF GRAFT-VERSUS-HOST DISEASE AFTER BONE-MARROW TRANSPLANTATION

Background. Graft-versus-host disease (GVHD) can be a major complicati on of allogeneic bone marrow transplantation even when the donor and r ecipient are siblings and share identical major histocompatibility ant igens. The explanation may be a mismatch of minor histocompatibility a ntigens. We previously characterized five minor histocompatibility ant igens, HA-1, 2, 3, 4, and 5, that are recognized by T cells in associa tion with the major histocompatibility antigens HLA-A1 and A2. Methods . We collected peripheral-blood leukocytes from 148 bone marrow recipi ents and their sibling donors, who were genotypically HLA identical. F ifty pairs were positive for HLA-A1, 117 were positive for HLA-A2, and 19 were positive for both. The pairs were typed with cytotoxic-T-cell clones specific for minor histocompatibility antigens HA-1, 2, 3, 4, and 5. Results. Mismatches of HA-3 were equally distributed among reci pients in whom GVHD developed and those in whom it did not. By contras t, a mismatch of only HA-1 was significantly correlated with GVHD of g rade II or higher (odds ratio, infinity; P = 0.02) in adults. One or m ore mismatches of HA-1, 2, 4, and 5 were also significantly associated with GVHD (odds ratio, infinity; P = 0.006) in adults. These associat ions were not observed in children. Conclusions. A mismatch of minor h istocompatibility antigen HA-1 can cause GVHD in adult recipients of a llogeneic bone marrow from HLA-identical donors. Prospective HA-1 typi ng may improve donor selection and identify recipients who are at high risk for GVHD. (C) 1996, Massachusetts Medical Society.