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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1147-1150.
Prepublished online as a Blood First Edition Paper on March 28, 2008; DOI 10.1182/blood-2007-12-129262.
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Submitted December 17, 2007
Accepted March 18, 2008
Analysis of regulatory T cell changes in patients with idiopathic thrombocytopenic purpura receiving B-cell depleting therapy with rituximab
Roberto Stasi*, Nichola Cooper, Giovanni Del Poeta, Elisa Stipa, Maria Laura Evangelista, Elisabetta Abruzzese, and Sergio Amadori
Department of Medical Sciences, Ospedale Regina Apostolorum, Albano Laziale, Italy
Molecular Immunology Unit, Institute of Child Health, London, United Kingdom
Department of Hematology, Tor Vergata University Hospital, Rome, Italy
Division of Hematology, Ospedale S. Eugenio, Rome, Italy
* Corresponding author; email: roberto.stasi{at}uniroma2.it.
The effects of B cell depletion with rituximab on regulatory T cells (Tregs) have not been determined. We investigated Tregs in patients receiving rituximab for chronic idiopathic thrombocytopenic purpura (ITP). The peripheral blood Tregs, identified as CD4+FOXP3+ T cells, were measured by flow cytometry prior to and after the immunotherapy. In addition, Tregs were analyzed for their usage of the T-cell receptor (TCR)  -variable (VB) region gene as well as their regulatory function as assessed by cell proliferation assays.
Pretreatment data revealed a reduced number and a defective suppressive capacity of Tregs in ITP patients as compared to control individuals. In addition, Tregs showed a polyclonal spectratype. Patients, particularly responders, showed restored numbers of Tregs as well as a restored regulatory function upon treatment with rituximab.
These results indicate that patients with active ITP have a defective T regulatory cell compartment that can be modulated by a B cell-targeted therapy.
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