Immunopathology and therapeutic immuno-intervention

Directeur : 

Sébastien Lacroix-Desmazes

Directeur adjoint : 

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.

Thèmes scientifiques

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.

Principales publications

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

IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. 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. Nat Med 26: 1096-1101. PMID: 32483358 link

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

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

Intravenous immunoglobulin induces IL-4 in human basophils by signaling through surface-bound IgE. 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. J Allergy Clin Immunol. 144: 524-535. PMID: 30529242 link

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

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