Research ArticleTransplantation

MHC-Resident Variation Affects Risks After Unrelated Donor Hematopoietic Cell Transplantation

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Science Translational Medicine  25 Jul 2012:
Vol. 4, Issue 144, pp. 144ra101
DOI: 10.1126/scitranslmed.3003974

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SNPing Away at Graft-Versus-Host Disease

The major histocompatibility complex (MHC) governs the acceptance or rejection of grafts. Donor-recipient matching of human leukocyte antigens (HLAs), which are found in the MHC, is critical not only to prevent transplant rejection but also to limit graft-versus-host disease (GVHD)—a side effect of blood cell transplant where the donor blood cells attack the recipient. GVHD is the leading cause of early complications and death after unrelated donor hematopoietic cell transplantation Transplants from related donor are preferred, because up to 80% of recipients of fully HLA-matched, but unrelated, donors develop GVHD. Now, Petersdorf et al. identify single-nucleotide polymorphisms (SNPs) within the MHC, but not in the HLA, that may contribute to the development of GVHD.

The authors scanned more than 4000 samples in HLA-matched donor-recipient pairs for MHC region SNPs that were not in the HLA. Outcome did not depend on the total number of SNPs; rather, specific SNPs contributed disproportionately. Of these, two SNPs were markers of disease-free survival and acute GVHD. Moreover, on the basis of the currently available donor pool, recipients may be able to further match SNPs before transplant to decrease their risk of GVHD. Thus, non-HLA SNP screening could improve patient outcome after hematopoietic transplantation.