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Prediction of autoimmune connective tissue disease in an at-risk cohort: prognostic value of a novel two-score system for interferon status
  1. Md Yuzaiful Md Yusof1,2,
  2. Antonios Psarras1,
  3. Yasser M El-Sherbiny1,3,
  4. Elizabeth M A Hensor1,2,
  5. Katherine Dutton1,
  6. Sabih Ul-Hassan1,
  7. Ahmed S Zayat1,
  8. Mohammad Shalbaf1,
  9. Adewonuola Alase1,
  10. Miriam Wittmann1,2,
  11. Paul Emery1,2,
  12. Edward M Vital1,2
  1. 1 Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds, UK
  2. 2 National Institute for Health Research (NIHR) Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
  3. 3 Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
  1. Correspondence to Dr Edward M Vital, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Chapel Allerton Hospital, Leeds LS7 4SA, UK; e.m.j.vital{at}leeds.ac.uk

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.

  • autoantibodies
  • autoimmune diseases
  • cytokines
  • sjøgren’s syndrome
  • systemic lupus erythematosus

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/

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Footnotes

  • MYMY and AP contributed equally.

  • Handling editor Josef S Smolen

  • Contributors MYMY, AP and EMV: substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data, drafting the work or revising it critically for important intellectual content, final approval of the version published and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. YME-S, EMAH, KD, SU-H, MS, AA, MW and PE: substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data, drafting the work or revising it critically for important intellectual content and final approval of the version published.

  • Funding This research was funded/supported by the National Institute for Health Research (NIHR) and NIHR Leeds Biomedical Research Centre based at Leeds Teaching Hospitals NHS Trust (DRF-2014-07-155 and CS-2013-13-032).

  • Disclaimer The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests EMV is an NIHR Clinician Scientist. He has received honoraria and research grant support from Roche, GSK and AstraZeneca. PE has received consultant fees from BMS, Abbott, Pfizer, MSD, Novartis, Roche and UCB. He has received research grants paid to his employer from Abbott, BMS, Pfizer, MSD and Roche. MW has received honoraria for educational activity and consultancy from Novartis, Janssen, Abbvie and Cellgene. ASZ has received honoraria from Roche/Chugai, BMS, Biogen and Menarini.

  • Patient consent Not required.

  • Ethics approval All individuals provided informed written consent and this research was carried out in compliance with the Declaration of Helsinki. The patients’ blood samples used for this study were collected under ethical approval, REC 10/H1306/88, National Research Ethics Committee Yorkshire and Humber–Leeds East, and healthy control participants’ peripheral blood was collected under the study number 04/Q1206/107. All experiments were performed in accordance with relevant guidelines and regulations. The University of Leeds was contracted with administrative sponsorship.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement None.

  • Correction notice This article has been corrected since it published Online First. The affiliations have been updated.

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