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Hallmark of Systemic Lupus Erythematosus: Role of B Cell Hyperactivity

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Pathogenesis of Systemic Lupus Erythematosus

Abstract

B cells have been the focus of systemic lupus erythematosus (SLE) research for the past two decades since they are acknowledged to play a central role in disease pathogenesis. This has been somewhat fruitful, yielding the approval in 2011 by the Food and Drug Administration of the only (as of today) biological therapy in SLE, belimumab, a humanised monoclonal antibody (mAb) targeting the key B cell survival factor B cell-activating factor of the tumour necrosis factor (TNF) family (BAFF). However, given the modest clinical benefit of this biological agent, this condition is still burdened by a lack of new targeted therapies, without which many patients will continue to suffer from severe manifestations of the disease leading to irreversible organ damage, affecting their quality of life while increasing morbidity and mortality. This is in stark contrast to other autoimmune diseases, such as rheumatoid arthritis, where a revolution of targeted treatments, which started more than a decade ago, led to a new era of therapeutic management. Facing this unacceptable situation, a comprehensive understanding of the perturbed B cell biology operative in SLE is crucial in order to fine-tune and develop new targeted therapy alternatives in a precision medicine approach. In this chapter, we will discuss the pivotal roles of B cells in SLE pathogenesis, particularly changes that are observed in B cell subsets, the presence of B cell hyperactivity and loss of tolerance, the clinical relevance and pathogenic roles of autoantibodies, the operative signalling pathways, the interplay between B and T cells, the B cell cytokine network, and B cell-associated genetic factors in SLE.

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Authors and Affiliations

  1. Rheumatology Research Group, School of Clinical Sciences at Monash Health, Centre for Inflammatory Diseases, Monash University, Clayton, VIC, 3168, Australia

    Fabien B. Vincent

  2. Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, VIC, 3000, Australia

    William A. Figgett

  3. Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia

    William A. Figgett

  4. Department of Immunology and Pathology, Central Clinical School, Alfred Research Alliance, Monash University, Melbourne, VIC, 3004, Australia

    Margaret L. Hibbs

Authors
  1. Fabien B. Vincent
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  2. William A. Figgett
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  3. Margaret L. Hibbs
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Correspondence to Fabien B. Vincent .

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Editors and Affiliations

  1. Department of Medicine, Monash University, Clayton, VIC, Australia

    Alberta Hoi

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Vincent, F.B., Figgett, W.A., Hibbs, M.L. (2021). Hallmark of Systemic Lupus Erythematosus: Role of B Cell Hyperactivity. In: Hoi, A. (eds) Pathogenesis of Systemic Lupus Erythematosus. Springer, Cham. https://doi.org/10.1007/978-3-030-85161-3_2

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