The IL-4 receptor α-chain variant Q576R is strongly associated with decreased kidney allograft survival

The involvement of the interleukin-4 (IL-4) pathway in B-lymphocyte activation and induction of a T helper 2 (Th2) cell response prompted us to investigate the influence of a recently described gain-of function mutation in the IL-4 receptor a-chain gene (IL-4R alpha; CD 124) on renal allograft survival. We developed a genotyping assay for the IL-4R alpha variant Q576R and investigated 203 renal transplant patients, all of whom underwent transplantation surgery at a single institution. The overall frequency of the IL-4R alpha variant Q576R in this group was 38.9% (79/203). The Kaplan-Meier method was used to estimate the graft survival of 156 patients with complete follow-up time of 24 months. Significantly higher graft survival rates (P=0.012, log-rank test) were found in patients with the wild-type IL-4 receptor (2-year graft survival 78.8%) as compared to patients with the IL-4R alpha variant Q576R (2-year graft survival 60.6%). Multifactorial cox regression analysis showed that this effect was independent of HLA matching, sex of donor and recipient, age of recipient, year of transplantation and preformed antibodies (P=0.017). These results indicate a strong association of the IL-4R alpha variant Q576R with kidney allograft loss. Genotyping of kidney allograft recipients for the IL-4R alpha variant may offer a simple method to identify high-risk patients in the post-transplantation period.