THU0015 TYPE I INTERFERON SIGNATURE PREDICTS PROGRESSION TO INFLAMMATORY ARTHRITIS IN ACPA+ AT-RISK INDIVIDUALS WITHOUT CLINICAL SYNOVITIS
Authors: L. Garcia-Montoya, Z. Wigston, A. Burska, K. Mankia, E. Vital, P. Emery
Journal: Annals of the Rheumatic Diseases (2020)

Background: Interferon (IFN) is known to play a role in the pathogenesis of many autoimmune diseases, among them, rheumatoid arthritis (RA). A study showed that two interferon-stimulated gene expression scores (IFN-Score-A and IFN-Score-B) can be used to predict progression to connective tissue disease (CTD) in at-risk individuals, positive for anti-nuclear antibodies (ANA+) [1]. This validated score could potentially be applied to individuals at-risk of RA. Objectives: To investigate the role of type I IFN in patients at-risk of RA and assess its potential role as a biomarker to predict progression to inflammatory arthritis (IA). Methods: PBMC samples were taken from 36 at-risk individuals positive for anti-citrullinated protein antibodies (ACPA+), with a non-specific musculoskeletal complaint but no clinical synovitis and a normal ultrasound scan at baseline (BL). 17 of them developed IA later on, and had a second sample taken at the moment of progression. The other 19 did not progress and had a second sample taken after 1 year. Expression of IFN stimulated genes was assessed using TaqMan. T-test was used to compare the expression of the genes at the two time points of each individual. Binary logistic regression was used to assess BL predictors of progression. Multivariable analysis was adjusted for confounders such as C-reactive protein (CRP) rheumatoid factor (RF) and ACPA titre. Results: Table 1 shows the list of tested genes. There were no differences in the gene expression of progressors at BL and at the moment of IA diagnosis. Similarly, no differences were found between the non-progressors at BL and after 1 year. Comparing BL samples from progressors and non-progressors, there was a trend to higher expression of IFN-score-B in the progressors (Mann Whitney p=0.055), whereas IFN-score-A was similarly expressed in both groups. This is similar to the results found in a cohort of ANA+ individuals at risk of progressing to CTD [1]. Multivariable analysis showed that IFN-score-B and RF titre were predictive for IA progression with an odds ratio (OR) of 2.18 (p=0.048) and OR 1.01 (p=0.035). Table 1. Interferon stimulated genes and scores A and B GENE IFN score GENE IFN score CCL8 BST2 CEACAM1 IFI16 CXCL10 IFIH1 GBP1 LAMP3 IFI27 NT5C3B IFI44 PHF11 IFI44L A SERPING1 B IFIT1 SOCS1 IRF7 SP100 ISG15 STAT1 RSAD2 TAP1 XAF1 TRIM38 UBE2L6 UNC93B1 Table 2. Baseline characteristics and predictors of progression Conclusion: These exploratory results suggest that IFN changes in IA progressors precede subclinical inflammation on ultrasound. A preliminary risk model shows that IFN-score-B could be useful to predict progression to IA in at-risk of RA individuals; however, these results require validation in a larger at-risk cohort. References: [1]Md Yusof MY. Ann. Rheum. Dis. 2018;77(10):1432-9. Disclosure of Interests: Leticia Garcia-Montoya: None declared, Zoe Wigston: None declared, Agata Burska: None declared, Kulveer Mankia: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp &amp; Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp &amp; Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor)