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The autoimmune disease-associated IL2RA locus is involved in the clinical manifestations of systemic sclerosis

Lookup NU author(s): Professor Jaap Van Laar


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Regulatory T cells (T-regs) are crucial in the maintenance of the immune tolerance and seem to have an important role in systemic sclerosis (SSc). The interleukin 2 receptor alpha (IL2RA) is an important T-reg marker, and polymorphisms of IL2RA gene are associated with a number of autoimmune diseases. Therefore, we aimed to investigate for the first time the association of the IL2RA locus in SSc. For this purpose, a total of 3023 SSc patients and 2735 matched healthy controls, from six European Caucasian cohorts, were genotyped for the IL2RA gene variants rs11594656, rs2104286 and rs12722495 using the TaqMan allelic discrimination technology. The overall meta-analysis reached statistical significance when the three polymorphisms were tested for association with SSc, the limited subtype (lcSSc) and anti-centromere auto-antibodies (ACAs). However, no significant P-values were obtained when the ACA-positive patients were removed from the SSc and lcSSc groups, suggesting that these associations rely on ACA positivity. The strongest association signal with ACA production was detected for rs2104286 (P-FDR 2.07 x 10(-4,) odds ratio = 1.30 (1.14-1.47)). The associations of rs11594656 and rs12722495 were lost after conditioning to rs2104286, and allelic combination tests did not evidence a combined effect, indicating that rs2104286 best described the association between IL2RA and ACA presence in SSc. Genes and Immunity (2012) 13, 191-196; doi:10.1038/gene.2011.72; published online 20 October 2011

Publication metadata

Author(s): Martin JE, Carmona FD, Broen JCA, Simeon CP, Vonk MC, Carreira P, Rios-Fernandez R, Espinosa G, Vicente-Rabaneda E, Tolosa C, Garcia-Hernandez FJ, Castellvi I, Fonollosa V, Gonzalez-Gay MA, Saez-Comet L, Portales RG, de la Pena PG, Fernandez-Castro M, Diaz B, Martinez-Estupinan L, Coenen M, Voskuyl AE, Schuerwegh AJ, Vanthuyne M, Houssiau F, Smith V, de Keyser F, De Langhe E, Riemekasten G, Witte T, Hunzelmann N, Kreuter A, Palm O, Chee MM, van Laar JM, Denton C, Herrick A, Worthington J, Koeleman BPC, Radstake TRDJ, Fonseca C, Martin J, Spanish Scleroderma Grp

Publication type: Article

Publication status: Published

Journal: Genes and Immunity

Year: 2012

Volume: 13

Issue: 2

Pages: 191-196

Print publication date: 01/02/2012

ISSN (print): 1466-4879

ISSN (electronic): 1476-5470

Publisher: Nature Publishing Group


DOI: 10.1038/gene.2011.72


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Funder referenceFunder name
Consejo Superior de Investigaciones Cientificas (CSIC)
Dutch Association of Research (NWO)
GEN-FER from Spanish Society of Rheumatology
Scleroderma Society
Dutch Arthritis Foundation
Raynaud's and Scleroderma Association
CTS-180Junta de Andalucia
CTS-4977Junta de Andalucia
SAF2009-11110Spanish Ministry of Science
RD08/0075(RIER) from Instituto de Salud Carlos III (ISCIII), Spain
WI 1031/6.1DFG