Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.

The IRF7 Region Is Associated with Anti-Centromere Autoantibody Production in Systemic Sclerosis Patients.

Carmona1,  F. David, Gutala2,  Ramana, Simeon3,  Carmen P., Carreira4,  Patricia E., Ortego-Centeno5,  Norberto, Vicente-Rabaneda6,  Esther, Garcia-Hernandez7,  Francisco J.

Consejo Superior de Investigaciones Científicas, Armilla (Granada), Spain
Gregorio Marañón Hospital, Madrid, Spain
Hospital de Cruces, UPV/EHU, Barakaldo, Spain, Barakaldo, Spain
UTHSC-Houston Medical School, Houston, TX
University of Texas Health Science Center at Houston, Houston, TX
Univ of Texas Health Science, Houston, TX
Consejo Superior de Investigaciones Científicas, Granada, Spain
The University of Texas Health Science Center, Houston, TX
Hospital Valle de Hebron, Barcelona, Spain
Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, Spain
Hospital Clínico San Cecilio, Granada, Spain
Hospital de la Princesa, Madrid, Spain
Hospital Virgen del Rocío, Sevilla, Spain
Hospital Universitario Madrid Norte Sanchinarro, Madrid, Spain
Hospital Puerta de Hierro, Madrid, Spain


The interferon (IFN) pathway plays a key role in the susceptibility to autoimmunity. For instance, type I IFNs were reported to have a central aetiopathogenic role in the development and progression of systemic lupus erythematosus (SLE), and a type I IFN signature has been also observed in patients with systemic sclerosis (SSc). Recent studies have reported an association between IRF7 and autoantibody production in SLE. To further explore the potential role of this genomic region in SSc, we studied whether five single-nucleotide polymorphisms (SNPs) within this locus were implicated in the susceptibility to the disease and its main specific features.


Two case-control sets of Caucasian origin from the US and Spain were analysed, comprising a total of 2316 SSc cases and 2347 healthy controls. A meta-analysis was performed to test the overall effect of these genetic variants on SSc.


The Mantel-Haenszel test under an allelic model revealed strong association signals in the ACA analysis for rs1131665 (PFDR=6.14×10-4, OR=0.78, CI 95% 0.68–0.89), rs4963128 (PFDR=6.14×10-4, OR=0.79, CI 95% 0.70–0.90), rs702966 (PFDR=3.83×10-3, OR=0.82, CI 95% 0.72–0.93) and rs2246614 (PFDR=3.83×10-3, OR=0.83, CI 95% 0.73–0.94). Significant P-values also were obtained when the global disease was tested; however, the statistical significance was lost when the ACA+ patients were excluded from the study, suggesting that these associations rely on ACA positivity. In addition, the combined analysis of the ACA+/ACA- comparison showed statistically significant differences between both SSc subgroups for rs1131665 (PFDR=0.015, OR=0.80, CI 95% 0.69–0.93), rs4963128 (PFDR=0.035, OR=0.85, CI 95% 0.74–0.98), and rs702966 (PFDR=0.029, OR=0.83, CI 95% 0.72–0.96). Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant.


Our data show that variation in the IRF7 genomic region is clearly associated with ACA susceptibility in SSc patients and, hence, it may represent a common risk factor for autoantibody production in autoimmune diseases.

To cite this abstract, please use the following information:
Carmona, F. David, Gutala, Ramana, Simeon, Carmen P., Carreira, Patricia E., Ortego-Centeno, Norberto, Vicente-Rabaneda, Esther, et al; The IRF7 Region Is Associated with Anti-Centromere Autoantibody Production in Systemic Sclerosis Patients. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1492

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