Response to B-cell depleting therapy with rituximab reverts the abnormalities of T-cell subsets in patients with idiopathic thrombocytopenic purpura.
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 Bcl-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
Roberto
R
Department of Medical Sciences, Ospedale Regina Apostolorum, Albano Laziale, Italy. roberto.stasi@uniroma2.it
Del Poeta
Giovanni
G
Stipa
Elisa
E
Evangelista
Maria Laura
ML
Trawinska
Margherita M
MM
Cooper
Nichola
N
Amadori
Sergio
S
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D001402:B-Lymphocytes / Q000187:drug effects; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D019674:Genes, T-Cell Receptor beta / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000187:drug effects; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D000069283:Rituximab; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000187:drug effects
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C494826:BAX protein, human; D053222:Fas Ligand Protein; D007155:Immunologic Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D000069283:Rituximab