Mismatches of minor histocompatibility antigens between HLA-identical donors and recipients and the development of graft-versus-host disease after bone marrow transplantation.
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 an 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, infinity; P = 0.02) in adults. One or more mismatches of HA-1, 2, 4, and 5 were also significantly associated with GVHD (odds ratio, infinity; 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.
Goulmy
E
E
Department of Immunohematology and Blood Bank, Leiden University Hospital, The Netherlands.
Schipper
R
R
Pool
J
J
Blokland
E
E
Falkenburg
J H
JH
Vossen
J
J
Gratwohl
A
A
Vogelsang
G B
GB
van Houwelingen
H C
HC
van Rood
J J
JJ
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D003601:Cytotoxicity Tests, Immunologic; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D006182:H-Y Antigen / Q000032:analysis; D006680:HLA Antigens / Q000032:analysis / Q000235:genetics; D015788:HLA-A1 Antigen / Q000032:analysis; D015789:HLA-A2 Antigen / Q000032:analysis; D006650:Histocompatibility Testing; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D008297:Male; D015778:Minor Histocompatibility Antigens / Q000032:analysis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic
D006182:H-Y Antigen; D006680:HLA Antigens; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D015778:Minor Histocompatibility Antigens