A7.9 Does Telomere Shortening in Women with Rheumatoid Arthritis Predict X Chromosome Inactivation Bias?. (25th February 2013)

• Record Type: Journal Article
• Authors: Kanaan, Sami Barna; Onat, Onur Emre; Balandraud, Nathalie; Azzouz, Doua F; Roudier, Jean; Ozcelik, Tayfun; Lambert, Nathalie C
• Is Part Of: Annals of the rheumatic diseases. Volume 72:Supplement 1(2013)
• Page Start: A51
• Page End: A51
• Publication Date: 2013-02-25
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2013-203221.9
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Rheumatoid Arthritis (RA), like most auto-immune diseases, is a female predominant disease. As a possible explanation for gender bias, we have previously shown that women with RA have non-random X chromosome inactivation (XCI) that could trigger autoimmunity (article in preparation). Intriguingly, this bias in XCI correlates with presence of the shared epitope (SE) and with disease duration. Also associated with presence of the SE, premature immunosenescence, characterised by shorter telomere length, has been described in peripheral blood cells from patients with RA [1]. Moreover, telomeric non coding RNAs have been reported to be enriched near the inactive X chromosome in mammals [2] indicating a potential link between telomere length and XCI. Objectives: In this context, we propose to test whether women with RA have shortened telomere length and whether that could influence the epigenetic mechanism of XCI. Methods: A total of 73 women with RA and 48 healthy women with no history of autoimmune diseases, who had previously been tested for XCI and HLA-genotyped, were evaluated for telomere length. The relative telomere length was estimated by real-time PCR as originally described by Cawthon [3] with the 2 - ∆∆ Ct method. Results: Preliminary results show that women with RA have smaller telomere length than healthy women, although the difference is modest (p = 0.07) and has to be adjusted for age on a larger cohort. Contrary to expectations, shorter telomere length is not correlated with skewed XCI status, disease duration or the presence of shared epitope in our small cohort. Conclusions: This preliminary study seems to confirm that women with RA have shorter telomeres than healthy women. Further telomere length measurements have to be done on a larger group of patients with RA and healthy controls, as well as HLA-genotyping them and evaluating their XCI status. This will be a step forward in understanding the relationship between immune senescence, female predisposition and genetic risk (SE) in RA. References: SO Schonland et al, Proc Natl Acad Sci U S A 100, 13471 (Nov 11, 2003). S Schoeftner, M A Blasco, Nat Cell Biol 10, 228 (Feb, 2008). RM Cawthon, Nucleic Acids Res 30, e47 (May 15, 2002).