Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants

Interleukin 1 (IL-1) is involved in various autoimmune and inflammatory dis eases. IL 1 receptor antagonist (IL-1Ra) Is the naturally occurring antagon ist to IL-1 alpha and -1 beta. Polymorphisms of IL-1 beta have been associa ted with variations in IL-1 beta production (nucleotides +3953 and -511). A variable number tandem repeat (VNTR) polymorphism in the IL-1Ra gene has b een associated (allele 2) with increased IL-1Ra production. We examined the se polymorphisms in human leucocyte antigen (HLA)-matched allogeneic bone m arrow transplant patients and donors, IL-1Ra VNTR (allele 2) in the donor g enotype was more frequent with milder acute graft-versus-host disease (aGvH D) 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 s ubgroup with cyclosporine monotherapy prophylaxis: donor possession of alle le 2 was again associated with milder aGvHD, grades 0-II (19 out of 38 tran splants), than grades III-IV (1 out of 14) (P = 0.0042) transplants, No ass ociation was found between the IL-1 beta -511 or IL-1 beta +3953 polymorphi sm and severity of GVHD. Recipient IL-1Ra VNTR genotype (allele 2) showed a strong trend towards association with aGvHD severity (P = 0.0697). Thus, t he donor genotype for the IL-1Ra polymorphism has an apparent protective ro le against acute GVHD following transplantation and may be an additional fa ctor for individual risk assessment for complications, including GvHD, post transplant.