Novel genetic association of Wegener's granulomatosis with the interleukin 10 gene.

Abstract

Wegener's granulomatosis (WG) is a necrotizing vasculitis characterized by clonal expansions of T cells and production of antibodies against proteinase 3. The disease is associated with expanded dinucleotide repeats in the cytotoxic T lymphocyte antigen 4 (CTLA-4) gene, suggesting that genetic variation(s) in T cell related gene(s) could contribute to the T cell hyperactivity in WG. We investigated the polymorphisms in the genes of 2 cytokines, interleukin 4 (IL-4) and IL-10, which are essential for the polarization of T cells towards Th2 development and for the Ig production by B cells. Polymorphisms in the genes coding for IL-10 and IL-4 were analyzed in 32-36 Swedish Caucasian patients and 109 ethnically matched healthy individuals. There was no association with the IL-4 gene. A CA repeat polymorphism in IL-10 gene, IL-10.G, was associated with the disease. This polymorphism has earlier been associated with high autoantibody production. Our results indicate that the IL-10 gene may influence the disease, perhaps by influencing the production of autoantibodies.