RESTORE IMMUNE TOLERANCE IN RHEUMATOID ARTHRITIS
Phone: +33 4 67 33 57 21
Experimental Arthritis mouse models with clinical and immune monitoring
Phenotypic and functional characterization of DC and Treg subsets
Immunomonitoring of patients treated by biotherapies
Dendritic cell and Treg differentiation
The research aims of my group is focusing on:
- Development of novel and effective immunotherapeutic tools in Rheumatoid Arthritis
- Elucidating the role of DCs and/or regulatory cells in physiological and pathological conditions.
- Identifying biomarkers of response to biotherapies.
Restore immune tolerance without inducing global immune suppression using innovative antigen (Ag)-specific therapeutic molecule is the main issue of the CURE RA consortium (2018-2022), a collaborative project between 4 academic teams and the Arthritis R&D company. As a proof of concept, we demonstrated during the last 5 years, that an innovative hybrid molecule composed with a recombinant Fc region of an Ab, “clicked” with a citrullinated peptide, is able to specifically eliminate anti-citrullinated protein antibodies (ACPA)-positive B cells in vitro and in vivo, using antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) mechanisms. These unpublished results allowed us to deposit 3 patents. This innovative approach makes it possible to eliminate specific autoreactive ACPA+ B cells in RA patient. More importantly, our work opens up a new field of targeted treatment for systemic autoimmune diseases. However, the major limitation of our pilot study is that it showed in vitro and in vivo specific elimination of ACPA+ B cells and lacked substantial evidence to prove the therapeutic effects of the approach in vivo. The objective of the current project is to advance our understanding of the role of ACPA+ B cells in the pathophysiology of RA and to validate our therapeutic innovative approach to Cure RA. The 3 aims of the project are : 1-To address the safety of the therapeutic potential in immunocompetent mice. 2- To develop ACPA dependent experimental model of arthritis and evaluate the therapeutic potential of the elimination of ACPA+ B cell. 3- To determine the efficiency and specificity of the therapeutic approach in humanized mice model
- Immune tolerance induction using DC vaccination or adoptive Treg cell therapy
- Induction of Treg cells in patients treated by biotherapies
- Characterization of Myeloid cells in synovial fluid from JIA patients