Prediction of autoimmune connective tissue disease in an at-risk cohort: Prognostic value of a novel two-score system for interferon status

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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-naive). Bloods and skin biopsy (non-lesional) were analysed for two interferonstimulated 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 nonprogressors, 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 AICTD. These interferon scores may allow stratification of individuals At-Risk of AI-CTD permitting early intervention for disease prevention and avoid irreversible organ damage.

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Yusof, M. Y. M., Psarras, A., El-Sherbiny, Y. M., Hensor, E. M. A., Dutton, K., Ul-Hassan, S., … Vital, E. M. (2018). Prediction of autoimmune connective tissue disease in an at-risk cohort: Prognostic value of a novel two-score system for interferon status. Annals of the Rheumatic Diseases, 77(10), 1432–1439. https://doi.org/10.1136/annrheumdis-2018-213386

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