Year of publication:
Journal title abbreviated:
J ALLERGY CLIN IMMUN
Journal title long:
Journal of allergy and clinical immunology
Abstract:This study presents the first genetic risk factor for the nonatopic type of eczema and indicates a primary role of IL-31-induced pruritus in the initiation of this disease, thus proposing a new target for the prevention and therapy of eczema.Our results lend strong support to an important role of IL-31 in the pathogenesis of nonatopic eczema.We found significant association of a common IL31 haplotype with the nonatopic type of eczema in all 3 study populations (combined P = 4.5 x 10(-5)). Analysis of PBMCs in healthy individuals revealed a strong induction IL31 mRNA expression on stimulation with anti-CD3 and anti-CD28 that was 3.8-fold higher in individuals homozygous for the risk haplotype (AA) in contrast to non-A haplotype carriers, suggesting that altered regulation of IL-31 gene expression is the disease-causing factor.We sequenced the entire IL-31 gene, including the promoter region, and determined the haplotype structure. Single nucleotide polymorphisms tagging the main haplotypes were genotyped in 3 independent European populations comprising 690 affected families. An association analysis of IL31 gene variants with atopic and nonatopic eczema was performed.We aimed to evaluate the importance of polymorphisms in the human IL-31 gene (IL31) in the genetic susceptibility to eczema.IL-31 is a novel cytokine that, when overexpressed in transgenic mice, induces severe itching dermatitis resembling human eczema.