Project #16636
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#16636 : Defining the effects of TNF-blockers and IL-17A-inhibitors on immune responses in spondyloarthritis patients, analysis of protein and gene expression signatures
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Name of Applicant : Lars Rogge
Date of application : 30-12-2020
Unit : Immunoregulation
Location : Metchnikoff, 5th floor, room 5022
Phone : 0786139836
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Project context and summary :

Anti-TNF therapy has proven effective to reduce inflammation and clinical symptoms in SpA, however, the high rate of non-responsiveness (30-40%) to TNFi exposes a substantial fraction of patients to side effects without clinical benefit, and it is still not possible to determine which patients will respond to TNF inhibitors (TNFi) before treatment initiation. The recent introduction of antibodies blocking IL-17A has expanded the therapeutic options for axial SpA (axSpA), as well as psoriasis and psoriatic arthritis. It is therefore important to develop tools to guide treatment decisions for patients affected by SpA and other chronic inflammatory diseases, to optimize clinical care and contain health care costs. This project builds on our recent work performed in collaboration with the Bioinfo Hub, in which we have defined the mechanisms of action of TNF-blockers and identified immune signatures correlating with therapeutic responses to anti-TNF therapy in SpA patients (Menegatti et al., 2020). We have measured whole blood immune responses to microbial and pathway-specific stimuli using TruCulture assays in 20 axSpA patients before or after treatment with IL-17A-inhibitors and 20 patients before and after anti-TNF therapy. Proteins in supernatants have been measured by Olink technology for protein profiling. Gene expression in cell pellets has been analyzed by RNA sequencing at the Biomics platform. A preliminary analysis of the RNA-Seq data has been performed by Etienne Kornobis and Thomas Cokelaer.

Related team publications :
Immune response profiling of patients with spondyloarthritis reveals signalling networks mediating TNF-blocker function in vivo. Menegatti S, Guillemot V, Latis E, Yahia-Cherbal H, Mittermüller D, Rouilly V, Mascia E, Rosine N, Koturan S, Millot GA, Leloup C, Duffy D, Gleizes A, Hacein-Bey-Abina S; Milieu Intérieur Consortium, Sellam J, Berenbaum F, Miceli-Richard C, Dougados M, Bianchi E, Rogge L. Ann Rheum Dis. 2020 Dec 2:annrheumdis-2020-218304. doi: 10.1136/annrheumdis-2020-218304. Online ahead of print.
Cellular and molecular profiling of T-cell subsets at the onset of human acute GVHD. Latis E, Michonneau D, Leloup C, Varet H, Peffault de Latour R; CRYOSTEM Consortium, Bianchi E, Socié G, Rogge L. Blood Adv. 2020 Aug 25;4(16):3927-3942. doi: 10.1182/bloodadvances.2019001032.
NFAT primes the human RORC locus for RORγt expression in CD4+ T cells. Yahia-Cherbal H, Rybczynska M, Lovecchio D, Stephen T, Lescale C, Placek K, Larghero J, Rogge L, Bianchi E. Nat Commun. 2019 Oct 16;10(1):4698. doi: 10.1038/s41467-019-12680-x.
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Project Type : Medium
Status : In Progress

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