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 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.