title: The IL-4 receptor alpha-chain variant Q576R is strongly associated with decreased kidney allograft survival.
abstract: 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 alpha-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.
authors.affiliation: Institute of Clinical Immunology and Transfusion Medicine, Justus-Liebig-University, Giessen, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hackstein
authors.forename: H
authors.initials: H
authors.lastname: Klüter
authors.forename: L
authors.initials: L
authors.lastname: Fricke
authors.forename: J
authors.initials: J
authors.lastname: Hoyer
authors.forename: G
authors.initials: G
authors.lastname: Bein
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D005838:Genotype; D006084:Graft Rejection / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D016030:Kidney Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014181:Transplantation Immunology / Q000235:genetics*; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D019948:Receptors, Interleukin-4