Markers in the promoter region of interleukin-10 (IL-10) gene in myasthenia gravis: implications of diverse effects of IL-10 in the pathogenesis of the disease.

摘要

Interleukin-10 (IL-10) is an important pleiotropic cytokine with both anti-inflammatory and B lymphocyte stimulating functions. The expression of IL-10 is tightly controlled. A bi-allelic polymorphism and 2 CA repeat microsatellites located in the promoter region of IL-10 gene were analysed in Swedish myasthenia gravis (MG) patients and ethnically matched healthy individuals. The prevalence of a 'high secretor' phenotype of IL-10 (IL-10 1 G/G) was higher in IL-1beta TaqI polymorphism allele 2 positive healthy individuals ('high secretor' phenotype for IL-1beta) than in healthy individuals negative for this allele. No such balance was found in MG patients. In one of the microsatellites, IL10.R, allele 112 was associated with patients having normal thymic histology. No relation of IL10.R allele 112 to proinflammatory cytokine gene polymorphisms and serum IgG, IgM and autoantibodies against nicotinic acetylcholine receptor (nAchR-Ab) was found. In another microsatellite, IL10.G, allele 134 was associated with patients having higher level of nAchR-Ab in their circulation. Our results demonstrated novel genetic markers within IL-10 gene indicating different mechanisms for IL-10 involved in the disease.