title: Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease.
abstract: Transplantation and pregnancy, in which two diploid genomes reside in one body, can each lead to diseases in which immune cells from one individual target antigens encoded in the other's genome. One such disease, graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation (HSCT, or bone marrow transplant), is common even after transplants between HLA-identical siblings, indicating that cryptic histocompatibility loci exist outside the HLA locus. The immune system of an individual whose genome is homozygous for a gene deletion could recognize epitopes encoded by that gene as alloantigens. Analyzing common gene deletions in three HSCT cohorts (1,345 HLA-identical sibling donor-recipient pairs), we found that risk of acute GVHD was greater (odds ratio (OR) = 2.5; 95% confidence interval (CI) 1.4-4.6) when donor and recipient were mismatched for homozygous deletion of UGT2B17, a gene expressed in GVHD-affected tissues and giving rise to multiple histocompatibility antigens. Human genome structural variation merits investigation as a potential mechanism in diseases of alloimmunity.
authors: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA. mccarroll@genetics.med.harvard.edu
authors: Steven A
authors: SA
authors: McCarroll
authors: James E
authors: JE
authors: Bradner
authors: Hannu
authors: H
authors: Turpeinen
authors: Liisa
authors: L
authors: Volin
authors: Paul J
authors: PJ
authors: Martin
authors: Shannon D
authors: SD
authors: Chilewski
authors: Joseph H
authors: JH
authors: Antin
authors: Stephanie J
authors: SJ
authors: Lee
authors: Tapani
authors: T
authors: Ruutu
authors: Barry
authors: B
authors: Storer
authors: Edus H
authors: EH
authors: Warren
authors: Bo
authors: B
authors: Zhang
authors: Lue Ping
authors: LP
authors: Zhao
authors: David
authors: D
authors: Ginsburg
authors: Robert J
authors: RJ
authors: Soiffer
authors: Jukka
authors: J
authors: Partanen
authors: John A
authors: JA
authors: Hansen
authors: Jerome
authors: J
authors: Ritz
authors: Aarno
authors: A
authors: Palotie
authors: David
authors: D
authors: Altshuler
mesh_terms: D016026:Bone Marrow Transplantation; D015331:Cohort Studies; D005260:Female; D017353:Gene Deletion; D015894:Genome, Human; D014453:Glucuronosyltransferase / Q000235:genetics; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D015778:Minor Histocompatibility Antigens; D011110:Polymorphism, Genetic
chemical_list: D006680:HLA Antigens; D015778:Minor Histocompatibility Antigens; D014453:Glucuronosyltransferase; C500513:UGT2B17 protein, human