Anti B cell therapy (rituximab) in the treatment of autoimmune diseases

Kazkaz, Hanadi; Isenberg, David

doi:10.1016/j.coph.2004.03.006

Cited by 73 publications

(52 citation statements)

References 25 publications

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“…In the New Zealand Black/White and New Zealand M2410 models, the presence of long-lived AFCs has been documented, and interestingly, they have been shown to reside at unique sites (83)(84)(85). Clearly, more studies are warranted to better understand what governs B cell fate decisions in healthy vs autoimmune settings, the outcome of which may have important implications for B cell depletion strategies currently used to treat human autoimmune diseases (86,87).…”

Section: Discussionmentioning

confidence: 99%

The Influence of Effector T Cells and Fas Ligand on Lupus-Associated B Cells

Fields

Nish

Hondowicz

et al. 2005

The Journal of Immunology

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Circulating autoantibodies against dsDNA and chromatin are a characteristic of systemic lupus erythematosus in humans and many mouse models of this disease. B cells expressing these autoantibodies are normally regulated in nonautoimmune-prone mice but are induced to secrete Abs following T cell help. Likewise, anti-chromatin autoantibody production is T cell-dependent in Fas/Fas ligand (FasL)-deficient (lpr/lpr or gld/gld) mice. In this study, we demonstrate that Th2 cells promote anti-chromatin B cell survival and autoantibody production in vivo. FasL influences the ability of Th2 cells to help B cells, as Th2-gld/gld cells support higher titers of anti-chromatin Abs than their FasL-sufficient counterparts and promote anti-chromatin B cell participation in germinal centers. Th1 cells induce anti-chromatin B cell germinal centers regardless of FasL status; however, their ability to stimulate anti-chromatin Ab production positively correlates with their level of IFN-γ production. This distinction is lost if FasL-deficient T cells are used: Th1-gld/gld cells promote significant titers of anti-chromatin Abs regardless of IFN-γ production levels. Thus, FasL from effector T cells plays an important role in determining the fate of anti-chromatin B cells.

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Section: Discussionmentioning

confidence: 99%

The Influence of Effector T Cells and Fas Ligand on Lupus-Associated B Cells

Fields

Nish

Hondowicz

et al. 2005

The Journal of Immunology

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“…Over the years, each of these cell types, as well as resident synovial fibroblasts, has been proposed as the driving force for the destructive process (1). The impressive therapeutic responses following B cell depletion by anti-CD20 antibodies strongly support the concept that RA is critically dependent on B lymphocytes, thereby pointing to a critical role for autoantibody generation, immune complexes, and T cell-B cell cooperation in disease pathogenesis (2)(3)(4).…”

mentioning

confidence: 89%

CXCR5‐ and CCR7‐dependent lymphoid neogenesis in a murine model of chronic antigen‐induced arthritis

Wengner

Höpken

Petrow

et al. 2007

Arthritis & Rheumatism

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Objective. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with unknown etiology and only partially defined pathogenesis. The aim of this study was to establish a murine model of chronic arthritis in which the development of tertiary lymphoid tissue, a hallmark of human RA, is locally induced, and to characterize the roles of the homeostatic chemokine receptors CXCR5 and CCR7 in this process.Methods. We developed a modified model of chronic antigen-induced arthritis (AIA) in mice with a strong bias toward inflammation. Disease pathology was assessed up to 9 months in wild-type, CXCR5-deficient, and CCR7-deficient mice by determination of knee joint swelling and cellular and humoral immune responses, as well as by histologic analysis of arthritic knee joints.Results. In this novel model of AIA, mice developed organized ectopic lymphoid follicles with topologically segregated B cell and T cell areas, high endothelial venules, and germinal center formation within the chronically inflamed synovial tissue. Analysis of the initiation and progression of AIA in wild-type, CXCR5 ؊/؊ , and CCR7 ؊/؊ mice revealed a reduction of acute inflammatory parameters in both knockout strains as well as significantly reduced joint destruction in CXCR5 ؊/؊ mice. Most importantly, the development and organization of tertiary lymphoid tissue were significantly impaired in CXCR5-deficient and CCR7-deficient mice.Conclusion. Our results suggest that an inflammatory microenvironment efficiently triggers lymphoid neogenesis in autoimmune diseases such as RA. Moreover, the generation of autoreactive tertiary lymphoid tissues, which is entirely dependent on homeostatic chemokines, may in turn maintain local aberrant chronic immune responses.

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“…It has been shown to reduce pre-B and B lymphocytes in vivo and has become an effective treatment for lymphomas and posttransplant lymphoproliferative disorders in adults and children. There are emerging data regarding the efficacy of rituximab in adults with rheumatoid arthritis or other autoimmune diseases (11)(12)(13)(14)(15). Although rituximab has been used effectively in children with non-Hodgkin's lymphoma and posttransplant lymphoproliferative disease, so far, only 1 published case report has been published describing the use of rituximab in a girl with SLE and refractory autoimmune thrombocytopenia (16).…”

mentioning

confidence: 99%

B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus

Marks¹,

Patey²,

Brogan³

et al. 2005

Arthritis & Rheumatism

144

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Objective. To determine the safety and efficacy of B lymphocyte depletion therapy in patients with refractory childhood-onset systemic lupus erythematosus (SLE).Methods. Seven patients (4 of whom were female), ages 7.7-16.1 years (median 14.8 years) with active SLE that was resistant to standard immunosuppressive agents were treated with B cell depletion. During a 2-week period, patients received two 750-mg/m 2 intravenous infusions of rituximab, with intravenous cyclophosphamide (if they had not previously received this treatment) and high-dose oral corticosteroids.Results. Patients were followed up for a median of 1.0 years, and no serious adverse effects were noted. In all patients, the clinical symptoms and signs for which rituximab therapy was initiated were improved. There was significant improvement in the British Isles Lupus Assessment Group global scores, from a median score of 22 (range 14-37) at baseline to a median score of 6 (range 4-11) at followup (P ‫؍‬ 0.002). In 2 patients with severe multisystem and life-threatening disease unresponsive to standard therapy (including plasma exchange), renal replacement therapy was successfully withdrawn following B cell depletion therapy. These 2 patients have subsequently shown further significant improvement in renal function and proteinuria.Conclusion. This open-label study demonstrates that targeted B cell depletion therapy can be a safe and efficacious addition to therapy with standard immunosuppressive agents in patients with refractory childhood SLE. The drugs used for treatment of childhood SLE need to be the most effective, least toxic agents, allowing normal growth and development.

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Anti B cell therapy (rituximab) in the treatment of autoimmune diseases

Cited by 73 publications

References 25 publications

The Influence of Effector T Cells and Fas Ligand on Lupus-Associated B Cells

The Influence of Effector T Cells and Fas Ligand on Lupus-Associated B Cells

CXCR5‐ and CCR7‐dependent lymphoid neogenesis in a murine model of chronic antigen‐induced arthritis

B lymphocyte depletion therapy in children with refractory systemic lupus erythematosus

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