AB0041 Heterogeneity of the type i interferon signature in rheumatoid arthritis may account for differences in its clinical relevance
Authors: J. Rodríguez-Carrio, M. Alperi-López, P. López, F.J. Ballina-Garcia, A. Suárez
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> increased expression of interferon-responding genes (IRGs), the so-called IFN signature, has been reported in rheumatoid arthritis (RA) in peripheral blood and synovial tissue. However, some controversy exists concerning its clinical relevance, since longitudinal changes of the IFN signature have been reported upon different treatments and a physiological diversification of the type I IFN signature among different conditions has been recently described. Additionally, the relevance of the IFN signature in the very early stage of RA is unknown. <h3>Objectives</h3> to evaluate (i) whether quantitative and qualitative differences in the activation of the IFN signature can be found in RA patients depending on the clinical stage and (ii) if these differences may be linked to a clinical relevance of the IFN signature. <h3>Methods</h3> expression of IFI44, IFI44L, IFI6 and MX1 was determined in peripheral blood in 98 RA patients and 28 controls. RA patients were classified into groups according to their clinical stage and treatments received: very early RA (VERA, recruited at onset and not exposed to any treatment), bDMARD-naïve (patients on csDMARD treatment) and bDMARD (patients on biological treatment, all anti-TNFα agents). An additional group of 13 RA patients candidate for TNFα-blockade was also recruited and samples were taken before and after anti-TNFα treatment. The associations among IRGs were evaluated by network and principal component analyses. <h3>Results</h3> all IRGs was increased in RA, although differences were noted among them. The IFN score was increased in all RA groups (VERA, bDMARD-naïve and bDMARD), but differences in their degree of activation and in the relationships among IRGs were observed. VERA patients exhibited a lower activation of the IFN signature and a distinct picture of the structure of the IRG network (figure 1) compared to both their established disease-counterparts and the HC group. The IFN score correlated the accumulated DAS28 over one year (r=0.593, p=0.025) and it was found to be a predictor of a good clinical outcome (EULAR good clinical response) in VERA (AUC=0.917, p=0.004). However, no differences in the IFN score were observed between the bDMARD-naïve and bDMARD groups, but opposite associations with the clinical parameters were noted. Interestingly, the correlations among IRGs delineate different pictures between these two groups. The IFN score at baseline predicted poor clinical outcome upon TNFα-blockade. Although no absolute changes in the IFN score were found, TNFα-blockade shifted the associations among IRGs. These differences mirrored those found when comparing bDMARD-naïve and bDMARD groups. <h3>Conclusions</h3> a certain heterogeneity within the IFN signature can be recognised in RA, depending on the clinical stage. The structure of the IFN signature may be a potential explanation for the controversy in this field and may represent a limitation for its use as a clinical biomarker. <h3>Disclosure of Interest</h3> None declared