title: Immunologic effects of rituximab on the human spleen in immune thrombocytopenia.
abstract: Immune thrombocytopenia (ITP) is an autoimmune disease with a complex pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has been shown to increase platelet counts in some ITP patients. From an immunologic standpoint, the mode of action of RTX and the reasons underlying its limited efficacy have yet to be elucidated. Because splenectomy is a cornerstone treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ was investigated in 18 spleens removed from ITP patients who were treated or not with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with secondary follicles. RTX therapy resulted in complete B-cell depletion in the blood and a significant reduction in splenic B cells, but these patients did not achieve remission. Moreover, whereas the percentage of circulating regulatory T cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive Tregs was increased in the spleens of patients who failed RTX therapy. These results indicate that although B cells are involved in ITP pathogenesis, RTX-induced total B-cell depletion is not correlated with its therapeutic effects, which suggests additional immune-mediated mechanisms of action of this drug.
authors.affiliation: CR Inserm 866, University of Burgundy, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Audia
authors.forename: Maxime
authors.initials: M
authors.lastname: Samson
authors.forename: Julien
authors.initials: J
authors.lastname: Guy
authors.forename: Nona
authors.initials: N
authors.lastname: Janikashvili
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fraszczak
authors.forename: Malika
authors.initials: M
authors.lastname: Trad
authors.forename: Marion
authors.initials: M
authors.lastname: Ciudad
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leguy
authors.forename: Sabine
authors.initials: S
authors.lastname: Berthier
authors.forename: Tony
authors.initials: T
authors.lastname: Petrella
authors.forename: Serge
authors.initials: S
authors.lastname: Aho-Glélé
authors.forename: Laurent
authors.initials: L
authors.lastname: Martin
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadié
authors.forename: Bernard
authors.initials: B
authors.lastname: Lorcerie
authors.forename: Patrick
authors.initials: P
authors.lastname: Rat
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cheynel
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Katsanis
authors.forename: Nicolas
authors.initials: N
authors.lastname: Larmonier
authors.forename: Bernard
authors.initials: B
authors.lastname: Bonnotte
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology* / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D000069283:Rituximab; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D007155:Immunologic Factors; D000069283:Rituximab