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Blood, 15 October 2007, Vol. 110, No. 8, pp. 2924-2930.
Prepublished online as a Blood First Edition Paper on June 4, 2007; DOI 10.1182/blood-2007-02-068999.
Previous Article | Next Article 
Submitted February 5, 2007
Accepted May 27, 2007
Response to B-cell depleting therapy with rituximab reverts the abnormalities of T cell subsets in patients with idiopathic thrombocytopenic purpura
Roberto Stasi*, Giovanni Del Poeta, Elisa Stipa, Maria Laura Evangelista, Margherita M Trawinska, Nichola Cooper, and Sergio Amadori
Dept. of Medical Sciences, Ospedale "Regina Apostolorum", Albano Laziale, Italy
Dept. of Hematology, "Tor Vergata" University Hospital, Rome, Italy
Division of Hematology, Ospedale "S. Eugenio", Rome, Italy
Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
* Corresponding author; email: roberto.stasi{at}uniroma2.it.
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) -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, pre-treatment abnormalities of T-cells in ITP patients included an increase of the Th1/Th2 ratio and of Tc1/Tc2 ratios (P<0.001), increased expression of Fas ligand on Th1 and Th2 cells (P<0.001), increased expression of Bcl-2 mRNA (P=0.003) and decreased expression of Bax mRNA (P=0.025) 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.

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