Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as idiopathic thrombocytopenic purpura (ITP). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of different peripheral blood T-cell subsets, the apoptosis profile, as well as the changes of T-cell receptor (TCR) beta-variable (VB) region gene usage of CD4(+) and CD8(+) T-cell subpopulations following rituximab therapy. The study involved 30 patients with chronic ITP who received rituximab, of whom 14 achieved a durable (> 6 months) response. Compared with the control group, pretreatment abnormalities of T cells in ITP patients included an increase of the Th1/Th2 ratio and of the Tc1/Tc2 ratios (P <.001), increased expression of Fas ligand on Th1 and Th2 cells (P <.001), increased expression of Bc1-2 mRNA (P =.003) and decreased expression of Bax mRNA (P =.025) in Th cells, and expansion of oligoclonal T cells with no preferential use of any TCR VB subfamily. These abnormalities were reverted in responders at 3 and 6 months after treatment, whereas they remained unchanged in nonresponders. Our findings indicate that in patients with ITP, response to B-cell depletion induced by rituximab is associated with significant changes of the T-cell compartment.

Stasi, R., Del Poeta, G., Stipa, E., Evangelista, M., Trawinska, M., Cooper, N., et al. (2007). Response to B-cell-depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. BLOOD, 110(8), 2924-2930 [10.1182/blood-2007-02-068999].

Response to B-cell-depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura

DEL POETA, GIOVANNI;AMADORI, SERGIO
2007

Abstract

Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as idiopathic thrombocytopenic purpura (ITP). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of different peripheral blood T-cell subsets, the apoptosis profile, as well as the changes of T-cell receptor (TCR) beta-variable (VB) region gene usage of CD4(+) and CD8(+) T-cell subpopulations following rituximab therapy. The study involved 30 patients with chronic ITP who received rituximab, of whom 14 achieved a durable (> 6 months) response. Compared with the control group, pretreatment abnormalities of T cells in ITP patients included an increase of the Th1/Th2 ratio and of the Tc1/Tc2 ratios (P <.001), increased expression of Fas ligand on Th1 and Th2 cells (P <.001), increased expression of Bc1-2 mRNA (P =.003) and decreased expression of Bax mRNA (P =.025) in Th cells, and expansion of oligoclonal T cells with no preferential use of any TCR VB subfamily. These abnormalities were reverted in responders at 3 and 6 months after treatment, whereas they remained unchanged in nonresponders. Our findings indicate that in patients with ITP, response to B-cell depletion induced by rituximab is associated with significant changes of the T-cell compartment.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/15 - Malattie del Sangue
English
FAS ligand; messenger RNA; protein bcl 2; rituximab; T lymphocyte receptor beta chain; adult; aged; apoptosis; article; B lymphocyte; CD4+ T lymphocyte; CD8+ T lymphocyte; cellular immunity; clinical article; controlled study; drug efficacy; drug mechanism; female; human; human cell; idiopathic thrombocytopenic purpura; immunopharmacology; male; priority journal; T lymphocyte subpopulation; Th1 cell; Th2 cell; Adult; Aged; Antibodies, Monoclonal; B-Lymphocytes; bcl-2-Associated X Protein; Fas Ligand Protein; Female; Flow Cytometry; Gene Expression; Genes, T-Cell Receptor beta; Humans; Immunologic Factors; Lymphocyte Depletion; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Purpura, Thrombocytopenic, Idiopathic; RNA, Messenger; T-Lymphocyte Subsets; T-Lymphocytes, Helper-Inducer
Stasi, R., Del Poeta, G., Stipa, E., Evangelista, M., Trawinska, M., Cooper, N., et al. (2007). Response to B-cell-depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura. BLOOD, 110(8), 2924-2930 [10.1182/blood-2007-02-068999].
Stasi, R; DEL POETA, G; Stipa, E; Evangelista, M; Trawinska, M; Cooper, N; Amadori, S
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/37989
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