Immunopathology and therapeutic immuno-intervention

Director : 

Sébastien Lacroix-Desmazes

Deputy Director : 

Jagadeesh Bayry

Our research focuses on immunoglobulin G (IgG) and pro-coagulant factor VIII (FVIII), derived from human plasma, which are used for therapeutic purposes. We Investigate their interactions with the immune system (i.e., their capacity to regulate or to be the target of immune responses), and with molecules in the microenvironment (co-factors, molecules of the complement system).

 

We are particularly interested in the putative consequences of these interactions on their structure, function and immunogenicity. Our aim is to translate our basic findings to the clinic, by developing new therapeutic molecules, or altering the existing protein therapeutics to reduce their immunogenicity.

Scientific Themes

Regulatory functions of normal IgG and regulatory cells in physiopathology

We investigate the role of IgG and regulatory T cells in immune homeostasis, immunotherapy of inflammatory diseases and vaccine response.

Cofactor-binding antibodies

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.

Immunogenicity of protein therapeutics

We investigate why some drug generate an immune response and we elaborate strategies to avoid or prevent it.

Main publications

Russick, J., S. Delignat, P. Milanov, O. Christophe, G. Boros, C. V. Denis, P. J. Lenting, S. V. Kaveri, and S. Lacroix-Demazes. 2020. Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII-encoding mRNA. Haematologica 105: 1129-1137. PMID: 31289204

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. PMID: 32483358

Rossini S, Noé R, Daventure V, Lecerf M, Justesen S, Dimitrov JD. 2020. V Region of IgG Controls the Molecular Properties of the Binding Site for Neonatal Fc Receptor. J Immunol. 205(10):2850-2860. PMID: 24404896

Kanyavuz A, Marey-Jarossay A, Lacroix-Desmazes S, Dimitrov JD. 2019. Breaking the law: unconventional strategies for antibody diversification. Nat Rev Immunol. Jun;19(6):355-368. PMID: 30718829

Galeotti C, Stephen-Victor E, Karnam A, Das M, Gilardin L, Maddur MS, Wymann S, Vonarburg C, Chevailler A, Dimitrov JD, Benveniste O, Bruhns P, Kaveri SV and Bayry J. 2019. Intravenous immunoglobulin induces IL-4 in human basophils by signaling through surface-bound IgE. J Allergy Clin Immunol. 144: 524-535. PMID: 30529242

Sharma M, Das M, Stephen-Victor E, Galeotti C, Karnam A, Maddur MS, Bruneval P, Kaveri SV and Bayry J. 2018. Regulatory T cells induce activation rather than suppression of human basophils. Science Immunology 3: Article number eaan0829. PMID: 29802207

All publications

Fundings