[HTML][HTML] Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone …
ELS Goulmy, R Schipper, J Pool… - … England Journal of …, 1996 - Mass Medical Soc
ELS Goulmy, R Schipper, J Pool, E Blokland, F Falkenburg, J Vossen, A Gratwohl…
New England Journal of Medicine, 1996•Mass Medical SocBackground 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 …
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 …
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.
The New England Journal Of Medicine