Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia

Sylvain Audia, Maxime Samson, Matthieu Mahévas, Christophe Ferrand, Malika Trad, Marion Ciudad, Alexandrine Gautheron, Famky Seaphanh, Vanessa Leguy, Sabine Berthier, Bruno Salles, Laurent Martin, Bernard Lorcerie, Pablo Ortega-Deballon, Olivier Facy, Denis Caillot, Agnès Soudry-Faure, Marc Michel, Bertrand Godeau, Nicolas LarmonierPhilippe Saas, Nona Janikashvili, Bernard Bonnotte

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

The pathogenic role of B cells in immune thrombocytopenia (ITP) has justified the therapeutic use of anti-CD20 antibodies such as rituximab (RTX). However, 60% of ITP patients do not respond to RTX. To decipher the mechanisms implicated in the failure of RTX, and because the spleen plays a well-recognized role in ITP pathogenesis, 12 spleens from ITP patients who had been nonresponders to RTX therapy were compared with 11 spleens from RTX-untreated ITP patients and 9 controls. We here demonstrate that in RTX-nonresponder ITP patients, preferential Th1 and Tc1 T lymphocyte polarizations occur, associated with an increase in splenic effector memory CD8+ T-cell frequency. Moreover, in the RTX-nonresponder patient group, the CD8+ T-cell repertoire displays a restricted pattern. In the blood, the phenotype of CD8+ T cells before and after RTX treatment is not modified in responders or nonresponders. Altogether, these results demonstrate for the first time an activation of splenic CD8+ T cells in ITP patients who did not respond to RTX and suggest their involvement in platelet destruction in these patients.

Original languageEnglish (US)
Pages (from-to)2477-2486
Number of pages10
JournalBlood
Volume122
Issue number14
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Audia, S., Samson, M., Mahévas, M., Ferrand, C., Trad, M., Ciudad, M., Gautheron, A., Seaphanh, F., Leguy, V., Berthier, S., Salles, B., Martin, L., Lorcerie, B., Ortega-Deballon, P., Facy, O., Caillot, D., Soudry-Faure, A., Michel, M., Godeau, B., ... Bonnotte, B. (2013). Preferential splenic CD8+ T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia. Blood, 122(14), 2477-2486. https://doi.org/10.1182/blood-2013-03-491415