Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo. Issue 4 (2nd December 2020)

• Record Type: Journal Article
• Authors: Menegatti, Silvia; Guillemot, Vincent; Latis, Eleonora; Yahia-Cherbal, Hanane; Mittermüller, Daniela; Rouilly, Vincent; Mascia, Elena; Rosine, Nicolas; Koturan, Surya; Millot, Gael A; Leloup, Claire; Duffy, Darragh; Gleizes, Aude; Hacein-Bey-Abina, Salima; Sellam, Jérémie; Berenbaum, Francis; Miceli-Richard, Corinne; Dougados, Maxime; Bianchi, Elisabetta; Rogge, Lars
• Other Names: author non-byline.; Abel Laurent author non-byline.; Alcover Andres author non-byline.; Aschard Hugues author non-byline.; Astrom Kalla author non-byline.; Bousso Philippe author non-byline.; Bruhns Pierre author non-byline.; Cumano Ana author non-byline.; Demangel Caroline author non-byline.; Deriano Ludovic author non-byline.; Santo James Di author non-byline.; Dromer Françoise author non-byline.; Eberl Gérard author non-byline.; Enninga Jost author non-byline.; Fellay Jacques author non-byline.; Gomperts-Boneca Ivo author non-byline.; Hasan Milena author non-byline.; Hercberg Serge author non-byline.; Lantz Olivier author non-byline.; Mouquet Hugo author non-byline.; Patin Etienne author non-byline.; Pellegrini Sandra author non-byline.; Pol Stanislas author non-byline.; Rausell Antonio author non-byline.; Rogge Lars author non-byline.; Sakuntabhai Anavaj author non-byline.; Schwartz Olivier author non-byline.; Schwikowski Benno author non-byline.; Shorte Spencer author non-byline.; Tangy Frédéric author non-byline.; Toubert Antoine author non-byline.; Trouvier Mathilde author non-byline.; Ungeheuer Marie-Noëlle author non-byline.; Duffy Darragh author non-byline.; Albert Matthew L author non-byline.; Quintana-Murci Lluis author non-byline.;
• Is Part Of: Annals of the rheumatic diseases. Volume 80:Issue 4(2021)
• Page Start: 475
• Page End: 486
• Publication Date: 2020-12-02
• Subjects: spondylitis -- ankylosing -- tumor necrosis factor inhibitors -- biological therapy -- immune system diseases; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2020-218304
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : 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.