6533b862fe1ef96bd12c6cd9

RESEARCH PRODUCT

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

Nona JanikashviliNona JanikashviliChristophe FerrandV. LeguyPhilippe SaasSabine BerthierDenis CaillotLaurent MartinLaurent MartinSylvain AudiaSylvain AudiaMarc MichelBruno SallesPablo Ortega-deballonBernard BonnotteBernard BonnotteBernard LorcerieMarion CiudadMarion CiudadAgnès Soudry-faureNicolas LarmonierMaxime SamsonMaxime SamsonMalika TradMalika TradMatthieu MahévasBertrand GodeauFamky SeaphanhFamky SeaphanhAlexandrine GautheronAlexandrine GautheronOlivier Facy

subject

AdultMaleImmunologyDrug ResistanceSpleenCD8-Positive T-LymphocytesLymphocyte ActivationReal-Time Polymerase Chain ReactionBiochemistryPathogenesisAntibodies Monoclonal Murine-DerivedYoung Adultimmune system diseaseshemic and lymphatic diseasesmedicineHumansImmunologic FactorsCytotoxic T cellAgedAged 80 and overPurpura Thrombocytopenic Idiopathicbiologybusiness.industryCell BiologyHematologyT lymphocyteMiddle AgedImmunohistochemistrymedicine.anatomical_structureImmunologyMonoclonalbiology.proteinFemaleRituximabAntibodyRituximabbusinessSpleenCD8medicine.drug

description

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.

yearjournalcountryeditionlanguage
2013-10-03Blood
https://doi.org/10.1182/blood-2013-03-491415