Preferential splenic CD8(+) T-cell activation in rituximab-nonresponder patients with immune thrombocytopenia.
Fiche publication
Date publication
octobre 2013
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BONNOTTE Bernard, Dr CAILLOT Denis, Dr FACY Olivier, Dr FERRAND Christophe, Pr MARTIN Laurent
Tous les auteurs :
Audia S, Samson M, Mahevas 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, Larmonier N, Saas P, Janikashvili N, Bonnotte B
Lien Pubmed
Résumé
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.
Référence
Blood. 2013 Oct 3;122(14):2477-86