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Targeting B cells with biologics in systemic lupus erythematosus.

ABSTRACT: The use of biologics as immune modulators in several autoimmune diseases has provided new tools to the physician's therapeutic armamentiarium and has led to improved patients' outcomes and quality of life. By producing autoantibodies, B cells in systemic lupus erythematosus (SLE) are key players in the pathogenesis of the disease and in its clinical manifestations. Therefore, biologics that target B cells in SLE aim at reducing the activity of these cells for the induction of remissions and/or amelioration of disease activity, reduction of organ involvement, and limitation of the complications and side effects caused by immunosuppressive therapies.This review describes the past and current clinical trials with B-cell-targeted biologics in SLE, to provide a historical perspective and the state-of-the-art on the topic.We review how the disappointment in the field from promising agents has been instrumental in providing valuable lessons leading to an improved design of new trials that are now giving encouraging results.In systemic lupus erythematosus (SLE), the use of B-cell-based biologics in clinical trials has shown both disappointment and promise.

SUBMITTER: La Cava A

PROVIDER: S-EPMC2962556 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Targeting B cells with biologics in systemic lupus erythematosus.

La Cava Antonio A

Expert opinion on biological therapy 20101004 11

<h4>Importance of the field</h4>The use of biologics as immune modulators in several autoimmune diseases has provided new tools to the physician's therapeutic armamentiarium and has led to improved patients' outcomes and quality of life. By producing autoantibodies, B cells in systemic lupus erythematosus (SLE) are key players in the pathogenesis of the disease and in its clinical manifestations. Therefore, biologics that target B cells in SLE aim at reducing the activity of these cells for the ...[more]

PMID: 20919800

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Project description:Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known outcomes or the potential for targeting these factors in SLE.

Dataset Information

Targeting B cells with biologics in systemic lupus erythematosus.

Publications

Targeting B cells with biologics in systemic lupus erythematosus.

Similar Datasets

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