Interleukin-35 is upregulated in systemic sclerosis and its serum levels are associated with early disease. (31st July 2015)

• Record Type: Journal Article
• Authors: Tomcik, Michal; Zerr, Pawel; Palumbo-Zerr, Katrin; Storkanova, Hana; Hulejova, Hana; Spiritovic, Maja; Kodet, Ondrej; Stork, Jiri; Becvar, Radim; Vencovsky, Jiri; Pavelka, Karel; Filkova, Maria; Distler, Jörg H. W.; Senolt, Ladislav
• Is Part Of: Rheumatology. Volume 54:Number 12(2015:Dec.)
• Page Start: 2273
• Page End: 2282
• Publication Date: 2015-07-31
• Subjects: interleukin-35 -- systemic sclerosis -- TGF-β -- disease duration -- capillaroscopy; Rheumatism -- Periodicals; Rheumatology -- Periodicals; 616.723005
• DOI: 10.1093/rheumatology/kev260
• Languages: English
• ISSNs: 1462-0324

Abstract

Abstract: Objectives. IL-35 is a member of the IL-12 family consisting of p35/IL-12a and EBI3/IL-27b subunits. IL-35 exerts immunomodulatory activities in experimental and human autoimmune inflammatory conditions. Our aim was to assess IL-35 expression in the skin and circulation of SSc patients and to characterize its potential association with SSc-related features. Methods. Expression of IL-35 in skin and dermal fibroblasts was quantified by quantitative PCR, immunohistochemistry and immunofluorescence. Serum levels of IL-35 (by ELISA), CRP (by turbidimetry), ANA (by immunofluorescence) and autoantibodies of the ENA complex (by immunoblot) were measured in 40 SSc patients. Serum IL-35 was determined in 40 age- and sex-matched healthy controls. Results. IL-35 expression was increased in SSc skin and dermal fibroblasts in a TGF-β-dependent manner. IL-35 induced an activated phenotype in resting fibroblasts and enhanced the release of collagen. IL-35 serum levels were increased in patients with SSc compared with healthy controls [median 83.9 (interquartile range 45.1–146.1) vs 36.2 (interquartile range 17.2–49.4) pg/ml, P < 0.0001]. Serum IL-35 was negatively correlated with disease duration ( r = −0.4339, P = 0.0052). In line with this finding, serum IL-35 was increased in patients with an early SSc pattern on capillaroscopy assessment compared with those with active and late SSc patterns. Conclusion. The present study demonstrates overexpression of IL-35 in SSc skin, dermal fibroblasts and serum. TGF-β induces IL-35, which in turn activates resting fibroblasts and enhances the release of collagen, thereby contributing to aberrant TGF-β signalling in SSc. Increased serum IL-35 is associated with early, inflammatory stages of SSc.