The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis

• Published in: Annals of the rheumatic diseases Vol. 75; no. 8; pp. 1567 - 1573
• Main Authors: Brkic, Zana, van Bon, Lenny, Cossu, Marta, van Helden-Meeuwsen, Cornelia G, Vonk, Madelon C, Knaapen, Hanneke, van den Berg, Wim, Dalm, Virgil A, Van Daele, Paul L, Severino, Adriana, Maria, Naomi I, Guillen, Samara, Dik, Willem A, Beretta, Lorenzo, Versnel, Marjan A, Radstake, Timothy
• Format: Journal Article
• Language: English
• Published: England 01.08.2016
• Subjects: Adult; Aged; B-Cell Activating Factor - biosynthesis; B-Cell Activating Factor - genetics; Case-Control Studies; Female; Fibrosis; Gene Expression Regulation; Humans; Interferon Type I - biosynthesis; Interferon Type I - genetics; Male; Middle Aged; Monocytes - metabolism; Peptide Fragments - biosynthesis; Peptide Fragments - blood; Procollagen - biosynthesis; Procollagen - blood; RNA, Messenger - genetics; Scleroderma, Systemic - genetics; Scleroderma, Systemic - metabolism; Skin - pathology; Transcriptome; Systemic Sclerosis; Inflammation; Cytokines; Autoimmune Diseases
• ISSN: 0003-4967; 1468-2060; 1468-2060
• DOI: 10.1136/annrheumdis-2015-207392

BackgroundInterferon (IFN) signature has been reported in definite systemic sclerosis (SSc) but it has not been characterised in early SSc (EaSSc). We aim at characterising IFN type I signature in SSc before overt skin fibrosis develops.MethodsThe expression of 11 IFN type I inducible genes was tested in whole-blood samples from 30 healthy controls (HCs), 12 subjects with primary Raynaud's phenomenon (RP), 19 patients with EaSSc, 7 patients with definite SSc without cutaneous fibrosis, 21 limited cutaneous SSc and 10 diffuse cutaneous SSc subjects. The correlation between IFN activity in monocytes, B cell activating factor (BAFF) mRNA expression and type III procollagen N-terminal propeptide (PIIINP) serum levels was tested.ResultsIn all the SSc groups, higher IFN scores were observed compared with HC. An IFN score ≥7.09 discriminated HCs from patients with SSc (sensitivity=0.7, specificity=0.88, area under receiving operating characteristic (AUROC)=0.82); the prevalence of an elevated IFN score was: HC=3.3%; RP=33.3%, EaSSc=78.9%, definite SSc=100%, limited cutaneous SSc=42.9%, diffuse cutaneous SSc=70.0%. In monocytes an IFN score ≥4.12 distinguished HCs from patients with fibrotic SSc (sensitivity=0.62, specificity=0.85, AUROC=0.76). Compared with IFN-negative subjects, IFN-positive subjects had higher monocyte BAFF mRNA levels (19.7±5.2 vs 15.20±4.0, p=2.1×10−5) and serum PIIINP levels (median=6.0 (IQR 5.4–8.9) vs median=3.9 (IQR 3.3–4.7), p=0.0004).ConclusionsAn IFN type I signature is observed in patients with SSc from the earliest phases of the disease, even before overt skin fibrosis. The presence of IFN type I signature in monocytes is correlated with BAFF mRNA expression and serum PIIINP levels, supporting a contribution in the pathogenesis and progression of SSc.