B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.

Sylvain Audia (1, 2, 3) , Marzia Rossato (3) , Malika Trad (2) , Maxime Samson (1, 2) , Kim Santegoets (3) , Alexandrine Gautheron (2) , Cornelis Bekker (3) , Olivier Facy (4) , Nicolas Cheynel (4) , Pablo Ortega-Deballon (4) , Mathieu Boulin (5) , Sabine Berthier (1) , Vanessa Leguy-Seguin (1) , Laurent Martin (2, 6) , Marion Ciudad (2) , Nona Janikashvili (2) , Philippe Saas (2) , Timothy Radstake (3) , Bernard Bonnotte (1, 2)

1 Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon]
2 RIGHT - Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098)
3 Laboratory of Translational Immunology [Utrecht, the Netherlands]
4 Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon)
5 Pharmacie [CHU de Dijon]
6 Service de Pathologie [CHU de Dijon]

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.

Mots clés: Immune thrombocytopenia; Rituximab; T follicular helper cells

Domaines: Immunologie

Sylvain Audia, Marzia Rossato, Malika Trad, Maxime Samson, Kim Santegoets, et al.. B cell depleting therapy regulates splenic and circulating T follicular helper cells in immune thrombocytopenia.. Journal of Autoimmunity, 2017, 77, pp.89-95. ⟨10.1016/j.jaut.2016.11.002⟩. ⟨hal-01556486⟩