title: Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis.
abstract: Rituximab, an anti-CD20 monoclonal antibody, has been used to treat autoimmune disorders such as mixed cryoglobulinemia (MC). However, its mechanisms of action as well as the effects on cellular immunity remain poorly defined. We investigated the changes of peripheral blood B- and T-cell subsets, the clonal VH1-69 cells, as well as the cytokine profile following rituximab therapy. The study involved 21 patients with hepatitis C-related MC who received rituximab, of whom 14 achieved a complete response. Compared with healthy and hepatitis C virus (HCV) controls, pretreatment abnormalities in MC patients included a decreased percentage of naive B cells (P < .05) and CD4(+)CD25(+)FoxP3(+) regulatory T cells (P = .02) with an increase in memory B cells (P = .03) and plasmablasts (P < .05). These abnormalities were reverted at 12 months after rituximab. Clonal VH1-69(+) B cells dramatically decreased following treatment (32% +/- 6% versus 8% +/- 2%, P = .01). Complete responders of rituximab exhibited an expansion of regulatory T cells (P < .01) accompanied with a decrease in CD8(+) T-cell activation (P < .01) and decreased production of interleukin 12 (IL-12; P = .02) and interferon-gamma (IFN-gamma; P = .01). Our findings indicate that in patients with MC, response to B-cell depletion induced by rituximab effectively normalizes many of the disturbances in peripheral B- and T-lymphocyte homeostasis.
authors.affiliation: Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Centre National de Recherche/Université Pierre et Marie Curie, Unité Médicale de Recherche 7087, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Saadoun
authors.forename: Michelle
authors.initials: M
authors.lastname: Rosenzwajg
authors.forename: Dan
authors.initials: D
authors.lastname: Landau
authors.forename: Jean Charles
authors.initials: JC
authors.lastname: Piette
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.forename: Patrice
authors.initials: P
authors.lastname: Cacoub
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D016175:B-Lymphocyte Subsets / Q000187:drug effects; D003449:Cryoglobulinemia / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000097:blood; D005434:Flow Cytometry; D006526:Hepatitis C / Q000150:complications; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007155:Immunologic Factors / Q000627:therapeutic use*; D008875:Middle Aged; D000069283:Rituximab; D016176:T-Lymphocyte Subsets / Q000187:drug effects; D014657:Vasculitis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D016207:Cytokines; D007155:Immunologic Factors; D000069283:Rituximab