Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status. Issue 10 (21st June 2018)

• Record Type: Journal Article
• Authors: Md Yusof, Md Yuzaiful; Psarras, Antonios; El-Sherbiny, Yasser M; Hensor, Elizabeth M A; Dutton, Katherine; Ul-Hassan, Sabih; Zayat, Ahmed S; Shalbaf, Mohammad; Alase, Adewonuola; Wittmann, Miriam; Emery, Paul; Vital, Edward M
• Is Part Of: Annals of the rheumatic diseases. Volume 77:Issue 10(2018)
• Page Start: 1432
• Page End: 1439
• Publication Date: 2018-06-21
• Subjects: autoantibodies -- autoimmune diseases -- cytokines -- sjøgren's syndrome -- systemic lupus erythematosus; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-213386
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objective: To evaluate clinical, interferon and imaging predictors of progression from 'At Risk' to autoimmune connective tissue diseases (AI-CTDs). Methods: A prospective observational study was conducted in At-Risk of AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months and treatment-naïve). Bloods and skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously described (IFN-Score-A and IFN-Score-B). Forty-nine healthy controls (HCs) and 114 SLE were used as negative and positive controls. Musculoskeletal ultrasound was performed. Progression was defined by meeting classification criteria for AI-CTDs at 12 months. Results: 118 individuals with 12-month follow-up were included. Of these, 19/118 (16%) progressed to AI-CTD (SLE=14, primary Sjogren's=5). At baseline, both IFN scores differed among At-Risk, HCs and SLE groups (p<0.001) and both were elevated in At-Risk who progressed to AI-CTD at 12 months versus non-progressors, to a greater extent for IFN-Score-B (fold difference (95% CI) 3.22 (1.74 to 5.95), p<0.001) than IFN-Score-A (2.94 (1.14 to 7.54); p=0.018). Progressors did not have significantly greater baseline clinical characteristics or ultrasound findings. Fold difference between At-Risk and HCs for IFN-Score-A was markedly greater in skin than blood. In multivariable logistic regression, only family history of autoimmune rheumatic disease, OR 8.2 (95% CI 1.58 to 42.53) and IFN-Score-B, 3.79 (1.50–9.58) increased the odds of progression. Conclusion: A two-factor interferon score and family history predict progression from ANA positivity to AI-CTD. These interferon scores may allow stratification of individuals At-Risk of AI-CTD permitting early intervention for disease prevention and avoid irreversible organ damage.