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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Md Yusof, MY, Psarras, A, El-Sherbiny, YM ORCID: https://orcid.org/0000-0003-4791-3475, Hensor, EMA, Dutton, K, Ul-Hassan, S, Zayat, AS, Shalbaf, M, Alase, A, Wittmann, M, Emery, P and Vital, EM, 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), pp. 1432-1439. ISSN 0003-4967

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Official URL: http://doi.org/10.1136/annrheumdis-2018-213386

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.

Item Type:	Journal article
Publication Title:	Annals of the Rheumatic Diseases
Creators:	Md Yusof, M.Y., Psarras, A., El-Sherbiny, Y.M., Hensor, E.M.A., Dutton, K., Ul-Hassan, S., Zayat, A.S., Shalbaf, M., Alase, A., Wittmann, M., Emery, P. and Vital, E.M.
Publisher:	BMJ Group
Date:	2018
Volume:	77
Number:	10
ISSN:	0003-4967
Identifiers:	Number Type 10.1136/annrheumdis-2018-213386 DOI
Rights:	This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018.
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	06 Feb 2019 11:14
Last Modified:	06 Feb 2019 15:26
URI:	https://irep.ntu.ac.uk/id/eprint/35771