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

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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‐1α and ‐1β. Polymorphisms of IL‐1β have been associated with variations in IL‐1β 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‐1β−511 or IL‐1β+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.

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