title: Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants.
abstract: Interleukin 1 (IL-1) is involved in various autoimmune and inflammatory diseases. IL-1 receptor antagonist (IL-1Ra) is the naturally occurring antagonist to IL-1alpha and -1beta. Polymorphisms of IL-1beta have been associated with variations in IL-1beta production (nucleotides +3953 and -511). A variable number tandem repeat (VNTR) polymorphism in the IL-1Ra gene has been associated (allele 2) with increased IL-1Ra production. We examined these polymorphisms in human leucocyte antigen (HLA)-matched allogeneic bone marrow transplant patients and donors. IL-1Ra VNTR (allele 2) in the donor genotype was more frequent with milder acute graft-versus-host disease (aGvHD) grades 0-II (29 out of 59 transplants) than severe GvHD grades III-IV (2 out of 18 transplants) (P = 0.0032). This association was confirmed in a subgroup with cyclosporine monotherapy prophylaxis: donor possession of allele 2 was again associated with milder aGvHD, grades 0-II (19 out of 38 transplants), than grades III-IV (1 out of 14) (P = 0.0042) transplants. No association was found between the IL-1beta -511 or IL-1beta +3953 polymorphism and severity of GvHD. Recipient IL-1Ra VNTR genotype (allele 2) showed a strong trend towards association with aGvHD severity (P = 0.0697). Thus, the donor genotype for the IL-1Ra polymorphism has an apparent protective role against acute GvHD following transplantation and may be an additional factor for individual risk assessment for complications, including GvHD, post transplant.
authors.affiliation: The Leukaemia Research Fund (LRF) Laboratory, Cookson Building, The Medical School, Newcastle-upon-Tyne, UK. Hannah.Cullup@ncl.ac.uk
authors.forename: H
authors.initials: H
authors.lastname: Cullup
authors.forename: A M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: G H
authors.initials: GH
authors.lastname: Jackson
authors.forename: P R
authors.initials: PR
authors.lastname: Taylor
authors.forename: J
authors.initials: J
authors.lastname: Cavet
authors.forename: P G
authors.initials: PG
authors.lastname: Middleton
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation / Q000379:methods*; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D011110:Polymorphism, Genetic; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D020080:Tandem Repeat Sequences / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: D007375:Interleukin-1; D017472:Receptors, Interleukin-1