TY - JOUR
T1 - Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation
AU - Goulmy, Els
AU - Schipper, Ronald
AU - Pool, Jos
AU - Blokland, Els
AU - Falkenburg, J. H.Frederik
AU - Vossen, Jaak
AU - Gratwohl, Alois
AU - Vogelsang, Georgia B.
AU - Van Houwelingen, Hans C.
AU - Van Rood, Jon J.
PY - 1996/2/1
Y1 - 1996/2/1
N2 - 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.
AB - 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.
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U2 - 10.1056/NEJM199602013340501
DO - 10.1056/NEJM199602013340501
M3 - Article
C2 - 8532022
AN - SCOPUS:13344278000
SN - 0028-4793
VL - 334
SP - 281
EP - 285
JO - New England Journal of Medicine
JF - New England Journal of Medicine
IS - 5
ER -