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Persistence of rituximab-resistant memory B cells contributes to relapses in adult patients with immunologic thrombocytopenia

Press release | 15 Apr 2021 - 11h00 | By INSERM PRESS OFFICE
Cell biology, development and evolution | Circulation, metabolism, nutrition

lymphocytes B

Image of a persistent germinal center (mouse spleen, 4 months after immunization), comprising B lymphocytes or memory B cells (green), strongly interacting with follicular dendritic cells (CD35, red), and follicular T helper cells (CD4, blue). ©Inserm/Reynaud, Claude-Agnès

Teams of Prof. Matthieu Mahévas from the reference center for autoimmune cytopenias in adults and the Mondor Biomedical Research Institute (Henri-Mondor AP-HP / Inserm / Université Paris-Est Créteil), Prof. Jean- Claude Weill and Dr Claude-Agnès Reynaud at the Institut Necker-Enfants Malades (Inserm / CNRS / University of Paris) studied the presence of self-reactive memory B lymphocytes before and after treatment with rituximab in adult patients with thrombocytopenia immunologic disease (ITP), a rare autoimmune disease.

The results of this study, which is the subject of a publication in the journal Science Translational Medicine on April 14, 2021 , show in particular that a fraction of memory B lymphocytes self-reactive towards platelet antigens resist treatment with rituximab, persist in the spleen for several months and participates in relapses. The discovery of these cells could open up new therapeutic avenues.    

Patients with B cell mediated autoimmune diseases, such as immunologic thrombocytopenia (ITP), may benefit from treatment with the anti-CD20 antibody, targeting B cells, rituximab. However, a significant proportion of patients relapse after this treatment.

The teams of Prof. Matthieu Mahévas from the internal medicine department of Henri-Mondor AP-HP hospital (Prof. Godeau and Prof. Michel), from the “Transfusion and red blood cell diseases” research unit of the Mondor Research Institute Biomedical (UPEC / Inserm), Prof. Jean-Claude Weill and Dr. Claude-Agnès Reynaud from the Necker-Enfants Malades Institute (Inserm / CNRS / University of Paris), in collaboration with numerous clinicians from the National Center for Auto Cytopenias -immunes of adults (CERECAI), sought to understand why by studying the presence of memory B lymphocytes reactive towards platelets in the spleen of patients splenectomized for a relapse of immunological thrombocytopenia after treatment with rituximab.

Several innovative experimental approaches have been carried out by Dr Crickx and Chappert in order to determine the phenotype, the transcriptional program and the specificity of these B cells capable of secreting anti-platelet antibodies in the spleen of patients during relapses. This work has made it possible to demonstrate that cells newly generated after B lymphocyte reconstitution and memory cells that have resisted treatment participate in relapses.

It thus appears that these pathogenic cells, resistant to rituximab, have lost the expression of CD20 on their surface but preserved the expression of CD19, specifically expressed by B lymphocytes, which could therefore constitute a new potential therapeutic target in this disease.

The persistence of immune memory is generally studied for the benefit it provides in terms of anti-infectious protection. This work demonstrates that memory cells can also persist during periods of remission of an autoimmune disease and contribute to subsequent relapses, suggesting new avenues to be explored to promote prolonged remissions in autoimmune diseases.

This work benefited from ANR funding (Auto-Immuni-B – ANR-18-CE15-0001).
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Press release – Inserm press room Persistence of rituximab-resistant memory B cells contributes to relapses in adult patients with immunologic thrombocytopenia Link : https://presse.inserm.fr/en/persistence-of-rituximab-resistant-memory-b-cells-contributes-to-relapses-in-adult-patients-with-immunologic-thrombocytopenia/42661/
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Rituximab-resistant splenic memory B cells and newly-engaged naive B cells fuel relapses in patients with immune thrombocytopenia

Etienne Crickx*, Pascal Chappert*, Aurélien Sokal, Sandra Weller, Imane Azzaoui, Alexis Vandenberghe, Guillaume Bonnard, Geoffrey Rossi, Tatiana Fadeev, Sébastien Storck, Jehane Fadlallah, Véronique Meignin, Etienne Rivière, Sylvain Audia, Bertrand Godeau, Marc Michel, Jean-Claude Weill, Claude-Agnès Reynaud, and Matthieu Mahévas

* These authors contributed equally

DOI : 10.1126/scitranslmed.abc3961

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