We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Donor-recipient mismatch for common gene deletion polymorphisms in graft-versus-host disease.
- Authors
McCarroll, Steven A.; Bradner, James E.; Turpeinen, Hannu; Volin, Liisa; Martin, Paul J.; Chilewski, Shannon D.; Antin, Joseph H.; Lee, Stephanie J.; Ruutu, Tapani; Storer, Barry; Warren, Edus H.; Bo Zhang; Lue Ping Zhao; Ginsburg, David; Soiffer, Robert J.; Partanen, Jukka; Hansen, John A.; Ritz, Jerome; Palotie, Aarno; Altshuler, David
- 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.
- Subjects
GRAFT versus host disease; IMMUNOLOGIC diseases; TRANSPLANTATION of organs, tissues, etc.; HUMAN genome; PREGNANCY; ANTIGENS; HEMATOPOIETIC stem cells
- Publication
Nature Genetics, 2009, Vol 41, Issue 12, p1341
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.490