title: B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.
abstract: B cells are involved in immune thrombocytopenia (ITP) pathophysiology by producing antiplatelet auto-antibodies. However more than a half of ITP patients do not respond to B cell depletion induced by rituximab (RTX). The persistence of splenic T follicular helper cells (TFH) that we demonstrated to be expanded during ITP and to support B cell differentiation and antiplatelet antibody-production may participate to RTX inefficiency. Whereas it is well established that the survival of TFH depends on B cells in animal models, nothing is known in humans yet. To determine the effect of B cell depletion on human TFH, we quantified B cells and TFH in the spleen and in the blood from ITP patients treated or not with RTX. We showed that B cell depletion led to a dramatic decrease in splenic TFH and in CXCL13 and IL-21, two cytokines predominantly produced by TFH. The absolute count of circulating TFH and serum CXCL13 also decreased after RTX treatment, whatever the therapeutic response. Therefore, we showed that the maintenance of TFH required B cells and that TFH are not involved in the inefficiency of RTX in ITP.
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France; Laboratory of Translational Immunology, University Medical Center, Utrecht, The Netherlands; Department of Internal Medicine and Clinical Immunology, Competence Center for Autoimmune Cytopenia, University Hospital, Dijon, France. Electronic address: sylvain.audia@u-bourgogne.fr.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.affiliation: Laboratory of Translational Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Marzia
authors.initials: M
authors.lastname: Rossato
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Trad
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France; Department of Internal Medicine and Clinical Immunology, Competence Center for Autoimmune Cytopenia, University Hospital, Dijon, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Samson
authors.affiliation: Laboratory of Translational Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Kim
authors.initials: K
authors.lastname: Santegoets
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France.
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Gautheron
authors.affiliation: Laboratory of Translational Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: Bekker
authors.affiliation: Department of Surgery, University Hospital, Dijon, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Facy
authors.affiliation: Department of Surgery, University Hospital, Dijon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cheynel
authors.affiliation: Department of Surgery, University Hospital, Dijon, France.
authors.forename: Pablo
authors.initials: P
authors.lastname: Ortega-Deballon
authors.affiliation: Department of Pharmacy, University Hospital, Dijon, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Boulin
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Competence Center for Autoimmune Cytopenia, University Hospital, Dijon, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Berthier
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Competence Center for Autoimmune Cytopenia, University Hospital, Dijon, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leguy-Seguin
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France; Department of Pathology, University Hospital, Dijon, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Ciudad
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France.
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Saas
authors.affiliation: Laboratory of Translational Immunology, University Medical Center, Utrecht, The Netherlands.
authors.forename: Timothy
authors.initials: T
authors.lastname: Radstake
authors.affiliation: CR INSERM 1098, University of Bourgogne/Franche-Comté, FHU INCREASE, France; Department of Internal Medicine and Clinical Immunology, Competence Center for Autoimmune Cytopenia, University Hospital, Dijon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000328:Adult; D000368:Aged; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D003131:Combined Modality Therapy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000097:blood / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy; D000069283:Rituximab / Q000627:therapeutic use; D013154:Spleen / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Immune thrombocytopenia; Rituximab; T follicular helper cells