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Volume 334:281-285 February 1, 1996 Number 5 Next

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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.

Source Information

From the Department of Immunohematology and Blood Bank (E.G., R.S., J.P., E.B.), the Department of Hematology (J.H.F.F.), the Department of Pediatrics (J.V.), the Department of Medical Statistics (H.C.H.), and Europdonor Foundation (J.J.R.), Leiden University Hospital, Leiden, the Netherlands; the Division of Hematology, Department of Research, Kantonsspital, Basel, Switzerland (A.G.); and Johns Hopkins Oncology Center, Baltimore (G.B.V.).

Address reprint requests to Dr. Goulmy at the Department of Immunohematology and Blood Bank, Leiden University Hospital, P.O. Box 9600, 2300 RC Leiden, the Netherlands.

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• GHREW, M H, RINGROSE, T, YOUNG, D, PETO, T (1999). Transfusion associated graft versus host disease. Heart 82: 255-256 [Full Text]  
• Eden, P. A., Christianson, G. J., Fontaine, P., Wettstein, P. J., Perreault, C., Roopenian, D. C. (1999). Biochemical and Immunogenetic Analysis of an Immunodominant Peptide (B6dom1) Encoded by the Classical H7 Minor Histocompatibility Locus. J. Immunol. 162: 4502-4510 [Abstract] [Full Text]  
• Mutis, T., Verdijk, R., Schrama, E., Esendam, B., Brand, A., Goulmy, E. (1999). Feasibility of Immunotherapy of Relapsed Leukemia With Ex Vivo-Generated Cytotoxic T Lymphocytes Specific for Hematopoietic System-Restricted Minor Histocompatibility Antigens. Blood 93: 2336-2341 [Abstract] [Full Text]  
• Dolstra, H., Fredrix, H., Maas, F., Coulie, P. G., Brasseur, F., Mensink, E., Adema, G. J., de Witte, T. M., Figdor, C. G., van de Wiel-van Kemenade, E. (1999). A Human Minor Histocompatibility Antigen Specific for B Cell Acute Lymphoblastic Leukemia. JEM 189: 301-308 [Abstract] [Full Text]  
• Middleton, P. G., Taylor, P. R.A., Jackson, G., Proctor, S. J., Dickinson, A. M. (1998). Cytokine Gene Polymorphisms Associating With Severe Acute Graft-Versus-Host Disease in HLA-Identical Sibling Transplants. Blood 92: 3943-3948 [Abstract] [Full Text]  
• Wolpert, E. Z., Grufman, P., Sandberg, J. K., Tegnesjo, A., Karre, K. (1998). Immunodominance in the CTL Response Against Minor Histocompatibility Antigens: Interference Between Responding T Cells, Rather than with Presentation of Epitopes. J. Immunol. 161: 4499-4505 [Abstract] [Full Text]  
• Malarkannan, S., Shih, P. P., Eden, P. A., Horng, T., Zuberi, A. R., Christianson, G., Roopenian, D., Shastri, N. (1998). The Molecular and Functional Characterization of a Dominant Minor H Antigen, H60. J. Immunol. 161: 3501-3509 [Abstract] [Full Text]  
• Maruya, E., Saji, H., Seki, S., Fujii, Y., Kato, K., Kai, S., Hiraoka, A., Kawa, K., Hoshi, Y., Ito, K., Yokoyama, S., Juji, T. (1998). Evidence That CD31, CD49b, and CD62L Are Immunodominant Minor Histocompatibility Antigens in HLA Identical Sibling Bone Marrow Transplants. Blood 92: 2169-2176 [Abstract] [Full Text]  
• Aractingi, S., Chosidow, O. (1998). Cutaneous Graft-versus-Host Disease. Arch Dermatol 134: 602-612 [Abstract] [Full Text]  
• Warren, E. H., Greenberg, P. D., Riddell, S. R. (1998). Cytotoxic T-Lymphocyte-Defined Human Minor Histocompatibility Antigens With a Restricted Tissue Distribution. Blood 91: 2197-2207 [Abstract] [Full Text]  
• den Haan, J. M., Meadows, L. M., Wang, W., Pool, J., Blokland, E., Bishop, T. L., Reinhardus, C., Shabanowitz, J., Offringa, R., Hunt, D. F., Engelhard, V. H., Goulmy, E. (1998). The Minor Histocompatibility Antigen HA-1: A Diallelic Gene with a Single Amino Acid Polymorphism. Science 279: 1054-1057 [Abstract] [Full Text]  
• Kernan, N. A., Dupont, B. (1996). Minor Histocompatibility Antigens and Marrow Transplantation. NEJM 334: 323-324 [Full Text]