Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation

Els Goulmy, Ronald Schipper, Jos Pool, Els Blokland, J. H.Frederik Falkenburg, Jaak Vossen, Alois Gratwohl, Georgia B. Vogelsang, Hans C. Van Houwelingen, Jon J. Van Rood

Research output: Contribution to journalArticlepeer-review

Abstract

Background. Graft-versus-host disease (GVHD) can be a major complication of allogeneic bone marrow transplantation even when the donor and recipient are siblings and share identical major histocompatibility antigens. The explanation may be a mismatch of minor histocompatibility antigens. We previously characterized five minor histocompatibility antigens, HA-1, 2, 3, 4, and 5, that are recognized by T cells in association with the major histocompatibility antigens HLA-A1 and A2. Methods. We collected peripheral- blood leukocytes from 148 bone marrow recipients and their sibling donors, who were genotypically HLA identical. Fifty 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 recipients in whom GVHD developed and those in whom it did not. By contrast, a mismatch of only HA-1 was significantly correlated with GVHD of grade II or higher (odds ratio, ∞; P=0.02) in adults. One or more mismatches of HA-1, 2, 4, and 5 were also significantly associated with GVHD (odds ratio, ∞; P=0.006) in adults. These associations were not observed in children. Conclusions. A mismatch of minor histocompatibility antigen HA-1 can cause GVHD in adult recipients of allogeneic bone marrow from HLA- identical donors. Prospective HA-1 typing may improve donor selection and identify recipients who are at high risk for GVHD.

Original languageEnglish (US)
Pages (from-to)281-285
Number of pages5
JournalNew England Journal of Medicine
Volume334
Issue number5
DOIs
StatePublished - Feb 1 1996

ASJC Scopus subject areas

  • Medicine(all)

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