B cell therapy in ANCA-associated vasculitis: current and emerging treatment options


Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an organ-threatening and life-threatening multi-system autoimmune disease in which B cell-derived ANCAs cause neutrophil activation and endothelial damage, strongly implicating these autoantibodies in the pathogenesis of AAV. B cell depletion with rituximab combined with glucocorticoids is associated with a reduction in ANCA concentrations and with clinical remission in the majority of patients with AAV. However, the safety profile of rituximab is no better than that of conventional therapy with cyclophosphamide, and long-term glucocorticoid treatment is needed to achieve and maintain disease-free remission. A need for new therapies exists to reduce the time to remission, to spare the use of glucocorticoids and to promote long-lasting remission without the risk of relapse. Over the past 20 years, there has been great interest in therapeutically targeting B cell cytokines, such as B cell-activating factor (BAFF), in many autoimmune disease settings. Dual B cell-targeted immunotherapy that combines B cell depletion and BAFF blockade could potentially be more efficacious than targeting either mechanism alone. In this Review, the theoretical background for use of this combination approach in AAV is presented and discussed.

Key points

  • B cell depletion therapy with rituximab is an effective alternative to cyclophosphamide for the induction of remission in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).

  • The safety profile of rituximab is not better than that of conventional therapy, suggesting that new therapies are needed to treat patients with AAV.

  • B cell-activating factor (BAFF), an essential cytokine in B cell survival and development, is associated with autoimmune disease, being present at high concentrations in patients with AAV.

  • Autoreactive B cells can be rescued from deletion in the presence of high concentrations of BAFF.

  • BAFF antagonism with belimumab is efficacious in patients with systemic lupus erythematosus and is undergoing evaluation in several other autoimmune diseases, including AAV.

  • Combination therapy with rituximab and belimumab is an attractive therapeutic strategy, as additional BAFF antagonism might enable effective early B cell depletion and reduce the re-emergence of autoreactive B cells.

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Fig. 1: Methods of therapeutically targeting B cells.
Fig. 2: Stages of B cell development and expression of cell surface receptors.
Fig. 3: BAFF in the production of ANCAs.

Change history

  • 02 November 2018

    In the section ‘Combining B cell-targeted therapies’ in the originally published version of this article, the 24-week interim analysis for the CALIBRATE study was incorrectly given as the 2- to 4-week interim analysis. This error has now been corrected in the HTML and PDF versions of the manuscript.


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The work of the authors is funded by a grant from GlaxoSmithKline (GSK) and the Medical Research Council (MRC) (grant number MR/R502145/1 to D.J. and R.J.). M.M. is in receipt of an MRC–GSK Experimental Medicine Initiative to Explore New Therapies (EMINENT) fellowship and S.G. is funded through the Experimental Medicine Training Initiative.

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Nature Reviews Rheumatology thanks D. Cornec and J. Thiel for their contribution to the peer review of this work.

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M.M. researched data for this article and wrote the manuscript. D.J., M.M. and R.J. made substantial contributions to discussion of content. All authors reviewed and/or edited the manuscript before submission.

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Correspondence to David Jayne.

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R.J. and D.J. declare that they have received financial support in the form of a grant from GlaxoSmithKline and the Medical Research Council towards an experimental medicine study evaluating the biological effects of combination therapy with rituximab and belimumab in anti-neutrophil cytoplasmic antibody-associated vasculitis. The other authors declare no competing interests.

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McClure, M., Gopaluni, S., Jayne, D. et al. B cell therapy in ANCA-associated vasculitis: current and emerging treatment options. Nat Rev Rheumatol 14, 580–591 (2018). https://doi.org/10.1038/s41584-018-0065-x

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