title: Effect of MHC and non-MHC donor/recipient genetic disparity on the outcome of allogeneic HCT.
abstract: The outcome of allogeneic hematopoietic cell transplantation is influenced by donor/recipient genetic disparity at loci both inside and outside the MHC on chromosome 6p. Although disparity at loci within the MHC is the most important risk factor for the development of severe GVHD, disparity at loci outside the MHC that encode minor histocompatibility (H) antigens can elicit GVHD and GVL activity in donor/recipient pairs who are otherwise genetically identical across the MHC. Minor H antigens are created by sequence and structural variations within the genome. The enormous variation that characterizes the human genome suggests that the total number of minor H loci is probably large and ensures that all donor/recipient pairs, despite selection for identity at the MHC, will be mismatched for many minor H antigens. In addition to mismatch at minor H loci, unrelated donor/recipient pairs exhibit genetic disparity at numerous loci within the MHC, particularly HLA-DP, despite selection for identity at HLA-A, -B, -C, and -DRB1. Disparity at HLA-DP exists in 80% of unrelated pairs and clearly influences the outcome of unrelated hematopoietic cell transplantation; the magnitude of this effect probably exceeds that associated with disparity at any locus outside the MHC.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. ehwarren@u.washington.edu
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Xinyi Cindy
authors.initials: XC
authors.lastname: Zhang
authors.forename: Shuying
authors.initials: S
authors.lastname: Li
authors.forename: Wenhong
authors.initials: W
authors.lastname: Fan
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.forename: Jason W
authors.initials: JW
authors.lastname: Chien
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boeckh
authors.forename: Lue Ping
authors.initials: LP
authors.lastname: Zhao
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
mesh_terms: D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000276:immunology*; D011379:Prognosis; D014019:Tissue Donors; D014184:Transplantation, Homologous