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

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 α (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 × 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.

Association of increased telomere lengths in limited scleroderma, with a lack of age-related telomere erosion.

OBJECTIVES: Telomere erosion, a feature of biological ageing, is implicated in a wide range of diseases. Its impact on autoimmune diseases remains unclear although autoantibodies against many telomere nucleoprotein components are prevalent in these diseases. We aimed to assess if telomere biology was abnormal in a cohort of patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: Telomere lengths in peripheral blood leucocytes (PBL) were determined using Southern blotting methods in a cohort of lcSSc subjects (n=43; age range 37-80 years) and a control population (n=107; age range 21-65 years). RESULTS: Telomere lengths in lcSSc subjects were longer than controls (p<0.001), did not show age-related telomere erosion and differed significantly from age-matched controls only after 50 years of age (p<0.001). CONCLUSIONS: This is the first report of maintenance of telomere lengths in an autoimmune disease state. These data indicate aberrant telomere biology and irregular biological ageing from the fifth decade of life. These findings provide insight into compromised DNA damage repair in lcSSc. Whether these observations indicate a causal or consequential relationship requires further investigation. This in turn, may provide potential novel targets for therapeutic intervention.