TY - JOUR T1 - Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis SP - 475 LP - 486 DO - 10.1136/annrheumdis-2020-218304 VL - 80 IS - 4 AU - Silvia Menegatti AU - Vincent Guillemot AU - Eleonora Latis AU - Hanane Yahia-Cherbal AU - Daniela Mittermüller AU - Vincent Rouilly AU - Elena Mascia AU - Nicolas Rosine AU - Surya Koturan AU - Gael A Millot AU - Claire Leloup AU - Darragh Duffy AU - Aude Gleizes AU - Salima Hacein-Bey-Abina AU - Milieu Intérieur Consortium AU - Jérémie Sellam AU - Francis Berenbaum AU - Corinne Miceli-Richard AU - Maxime Dougados AU - Elisabetta Bianchi AU - Lars Rogge Y1 - 2021/04/01 UR - http://ard.bmj.com/content/80/4/475.abstract N2 - Objectives Antitumour necrosis factor (TNF) therapy has revolutionised treatment of several chronic inflammatory diseases, including spondyloarthritis (SpA). However, TNF inhibitors (TNFi) are not effective in all patients and the biological basis for treatment failure remains unknown. We have analysed induced immune responses to define the mechanism of action of TNF blockers in SpA and to identify immunological correlates of responsiveness to TNFi.Methods Immune responses to microbial and pathway-specific stimuli were analysed in peripheral blood samples from 80 patients with axial SpA before and after TNFi treatment, using highly standardised whole-blood stimulation assays. Cytokines and chemokines were measured in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, and gene expression was monitored using nCounter assays.Results Anti-TNF therapy induced profound changes in patients’ innate immune responses. TNFi action was selective, and had only minor effects on Th1/Th17 immunity. Modular transcriptional repertoire analysis identified prostaglandin E2 synthesis and signalling, leucocyte recirculation, macrophage polarisation, dectin and interleukin (IL)-1 signalling, as well as the nuclear factor kappa B (NF-kB) transcription factor family as key pathways targeted by TNF blockers in vivo. Analysis of induced immune responses before treatment initiation revealed that expression of molecules associated with leucocyte adhesion and invasion, chemotaxis and IL-1 signalling are correlated with therapeutic responses to anti-TNF.Conclusions We show that TNFi target multiple immune cell pathways that cooperate to resolve inflammation. We propose that immune response profiling provides new insight into the biology of TNF-blocker action in patients and can identify signalling pathways associated with therapeutic responses to biological therapies. ER -