Immunopathology and therapeutic immuno-intervention

Director : 

Sébastien Lacroix-Desmazes

Deputy Director : 

Jagadeesh Bayry

Our team develops multidisciplinary research activities with a focus on the immunology, immunopathology of autoimmune diseases and immunotherapy. We aim at understanding fundamental mechanisms underlying the development of chronic autoimmune diseases and the development of anti-drug antibodies. With thus include experts in the fields of “Immunogenicity of protein therapeutics” with a focus on hemophilia A (S. Lacroix-Desmazes), of “Canonical and non-canonical functions of immunoglobulins” (J. D. Dimitrov), and of systemic autoimmune disorders, including thrombotic thrombocytopenic purpura (P. Coppo), systemic sclerosis and vasculitis (L. Mouthon).

In these diseases, we identify molecular signatures in specific cell populations (e.g., fibroblasts, antigen-specific B cells) from cohorts of patients and using dedicated animal models, to better understand pathogenesis. We look for biomarkers of disease progression and/or response to treatment, and develop immuno-intervention strategies to confer specific immune tolerance, or, conversely, boost protective immune responses. Our ultimate goal is to develop a transversal research towards the development of more targeted therapies and personalized medicine. Our research is steered by a constant interplay between our previous research activities, the personal scientific interests of the PIs in the team, the identification of societal and clinical unmet needs and the progresses in our respective research fields.

Scientific Themes

Immunogenicity of protein therapeutics

We aim at understanding the reasons for unexpected immunogenicity of some therapeutic proteins and develop original methods to foster long-lasting and specific immune tolerance.

Canonical and non-canonical functions of immunoglobulins

Investigation of the physicochemical mechanisms of antibodies specificity and polyspecificity. Molecular mechanisms and biological consequences of the interaction of antibodies with low molecular weight cofactor molecules.

Thrombotic thrombocytopenic purpura

Systemic autoimmune diseases

Main publications

Sharma, M., Das, M., Stephen-Victor, E., Galeotti, C., Karnam, A., Maddur, M.S., Bruneval, P., Kaveri, S., Bayry, J. 2018. Regulatory T cells induce activation rather than suppression of human basophils. Science Immunol, 3 (23), pp.eaan0829 Link

Lecerf M, Kanyavuz A, Rossini S, Dimitrov JD. 2021. Interaction of clinical-stage antibodies with heme predicts their physiochemical and binding qualities. Commun Biol. 2021 Mar 23;4(1):391 Link

Coppo P et al. 2021. A regimen with caplacizumab, immunosuppression, and plasma exchange prevents unfavorable outcomes in immune-mediated TTP. Blood, 11;137(6):733-742 Link

Sekar, R., A. Mimoun, M. Bou-Jaoudeh, S. Loyau, S. Delignat, V. Daventure, P. Bonilla, A. S. Bahle, K. Venkataraman, J. Rayes, Y. Boulaftali, M. Jandrot-Perrus, V. Proulle, and S. Lacroix-Desmazes. 2024. High FVIII concentrations interfere with GPVI-mediated platelet activation in vitro. J. Thromb. Haemost. JTH S1538-7836(24)00062-X Link

Mimoun, A., M. Bou-Jaoudeh, S. Delignat, V. Daventure, A. Reyes Ruiz, M. Lecerf, A. Azam, R. Noe, I. Peyron, O. D. Christophe, P. J. Lenting, V. Proulle, J. McIntosh, A. C. Nathwani, J. D. Dimitrov, C. V. Denis, and S. Lacroix-Desmazes. 2023. Transplacental delivery of therapeutic proteins by engineered immunoglobulin G: a step toward perinatal replacement therapy. J. Thromb. Haemost. JTH 21: 2405–2417 Link

Bou-Jaoudeh, M., A. Mimoun, S. Delignat, I. Peyron, L. Capdevila, V. Daventure, C. Deligne, J. D. Dimitrov, O. D. Christophe, C. V. Denis, P. J. Lenting, V. Proulle, and S. Lacroix-Desmazes. 2023. Imlifidase, a new option to optimize the management of patients with hemophilia A on emicizumab. J. Thromb. Haemost. JTH 21: 2776–2783 Link

Bou-Jaoudeh, M., S. Delignat, V. Daventure, J. Astermark, H. Lévesque, J. D. Dimitrov, C. Deligne, V. Proulle, and S. Lacroix-Desmazes. 2023. The IgG-degrading enzyme, Imlifidase, restores the therapeutic activity of FVIII in inhibitor-positive hemophilia A mice. Haematologica 108: 1322–1334 Link

Russick, J., S. Delignat, P. Milanov, O. Christophe, G. Boros, C. V. Denis, P. J. Lenting, S. V. Kaveri, and S. Lacroix-Desmazes. 2020. Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII-encoding mRNA. Haematologica 105: 1129–1137 Link

Delignat, S., J. Rayes, S. Dasgupta, B. Gangadharan, C. V. Denis, O. D. Christophe, J. Bayry, S. V. Kaveri, and S. Lacroix-Desmazes. 2020. Removal of Mannose-Ending Glycan at Asn2118 Abrogates FVIII Presentation by Human Monocyte-Derived Dendritic Cells. Front. Immunol. 11: 393 Link

Leborgne, C., E. Barbon, J. M. Alexander, H. Hanby, S. Delignat, D. M. Cohen, F. Collaud, S. Muraleetharan, D. Lupo, J. Silverberg, K. Huang, L. van Wittengerghe, B. Marolleau, A. Miranda, A. Fabiano, V. Daventure, H. Beck, X. M. Anguela, G. Ronzitti, S. M. Armour, S. Lacroix-Desmazes*, and F. Mingozzi*. 2020. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med 26: 1096-1101. (*: co-corresponding authors) Link

Varthaman, A., Lacroix-Desmazes, S. Pathogenic immune response to therapeutic factor VIII: exacerbated response or failed induction of tolerance? 2019. Haematologica. 104 (2): 236-244 Link

All publications