IL10R1 loss-of-function alleles in rheumatoid arthritis and systemic lupus erythematosus

• Published in: Clinical and experimental rheumatology 2009-07, Vol.27 (4), p.603-608
• Main Authors: HERMANN, J, GRUBER, S, NEUFELD, J. B, GRUNDTNER, P, GRANINGER, M, GRANINGER, W. B, BERGHOLD, A, GASCHE, C
• Format: Article
• Language: English
• Subjects: Antigens, CD - genetics; Antigens, CD - metabolism; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Biological and medical sciences; Clone Cells; Diseases of the osteoarticular system; Female; Gene Expression; Gene Silencing; Genetic Predisposition to Disease; HeLa Cells; Humans; Inflammatory joint diseases; Interleukin-10 - genetics; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signaling Lymphocytic Activation Molecule Family Member 1; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins - genetics; Suppressor of Cytokine Signaling Proteins - metabolism; Transfection
• ISSN: 0392-856X; 1593-098X

IL-10 is a pleiotropic cytokine involved in the regulation of innate and cell-mediated immunity and a key mediator within the disturbed SLE immune system. IL-10 binds to IL10R1, which is expressed on a variety of immune cells and activates the JAK-STAT pathway. Two (out of several known) genetic IL10R1 variants may alter IL-10 binding or signal transduction. Here we investigate the differential activity of these IL10R1 variants and their possible association with RA or SLE susceptibility. IL10R1-wt, IL10R1-S138G, IL10R1-G330R, or IL10R1- S138G +G330R were cloned into pIRESpuro3 and transfected into HeLa cells. Single cell clones were tested for IL-10-induced SOCS3- and SLAM gene expression by real-time PCR. DNA from 182 RA patients, 222 SLE patients, and 250 healthy controls was genotyped by allele-specific PCR. A biphasic increase of SOCS3 mRNA was observed that peaked at 15 minutes and 4 hours after IL-10 stimulation. The presence of IL10R1 S138G and G330R showed a weaker induction of both SOCS3 and SLAM upon stimulation with IL-10. In RA a homozygous G330R genotype was more commonly present than in controls (15.4% vs. 7.6%; p