Project

Go Back to Project List
#3747 : Defining the mechanisms of action of biologic therapies in spondyloarthritis
Topics: Transcriptomics (Illumina)
Origin: IP
Project type: Service

Name of Applicant: Lars Rogge
Date of application: 06-02-2020
Unit: Immunoregulation
Location: Metchnikoff – 5th floor – room 5022
Phone: 0140613822
@ Mail: lars.rogge@pasteur.fr

Project context and summary:

Spondyloarthritis (SpA) is a common chronic inflammatory rheumatic disease, with a prevalence of about 0.5%. In addition to the disabling rheumatic manifestations, some SpA patients develop severe extra-articular manifestations such as inflammatory bowel disease, uveitis and psoriasis. SpA mainly affects young adults and the functional consequences of inadequately controlled disease alter both their quality of life and their professional capacity with direct impact on healthcare costs.

The proinflammatory cytokines TNF and IL-17A are pivotal pathogenic cytokines in SpA and the introduction of biological therapies targeting these two cytokines has revolutionized the treatment of this disease. However, 30 to 40% of patients do not respond to these agents, and are exposed to the potential side-effects of the drugs without clinical benefit. The reasons underlying unresponsiveness are not known and it is currently not possible to predict therapeutic responses to these therapies. Defining the mechanisms of action of TNF-blockers and IL-17A inhibitors and developing personalized treatment strategies for patients affected by SpA and other chronic inflammatory diseases are therefore urgent medical and societal needs.

The premise of this project is that therapeutic outcome is defined by the unique interaction of the drug with the biological characteristics of each patient. Improved understanding of the molecular mechanisms of drug action in individual patients is key for the successful implementation of personalized treatment strategies and may identify novel therapeutic targets. In this project, we perform a comprehensive characterization of the cellular, functional and molecular effects of TNF-blockers and IL-17A-inhibitors on immune responses in SpA patients.


Related team publications:
H. Yahia-Cherbal, M. Rybczynska, D. Lovecchio, T. Stephen, C. Lescale, K. Placek, J. Larghero, L. Rogge, E. Bianchi, NFAT primes the human RORC locus for RORgammat expression in CD4(+) T cells. Nature communications 10, 4698 (2019).
S. Menegatti, E. Bianchi, L. Rogge, Anti-TNF Therapy in Spondyloarthritis and Related Diseases, Impact on the Immune System and Prediction of Treatment Responses. Front Immunol 10, 382 (2019).
M. Coffre, M. Roumier, M. Rybczynska, E. Sechet, H. K. Law, L. Gossec, M. Dougados, E. Bianchi, L. Rogge, Combinatorial control of Th17 and Th1 cell functions by genetic variations in genes associated with the interleukin-23 signaling pathway in spondyloarthritis. Arthritis and rheumatism 65, 1510-1521 (2013).
Service Delivery
Manager: valerie.briolat@pasteur.fr
Status: Closed


Go Back to Project List