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Are autoantibodies the targets of B-cell-directed therapy?

Nature Reviews Rheumatology volume 7, pages 551–556 (2011)Cite this article

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Abstract

B-cell-directed therapy—the use of agents that eliminate B cells or block cytokines important for B-cell function—is emerging as a promising approach to the treatment of rheumatic disease. Target diseases, including systemic lupus erythematosus (SLE), display diverse patterns of autoantibody production and aberrant activation of B cells. Despite the success of this general approach, the mechanisms by which B-cell-directed therapy ameliorates disease, and the role of autoantibodies as biomarkers of clinical response remain unclear. Importantly, although B-cell-directed therapy can reduce the production of some autoantibodies, the effects can be variable and heterogeneous, probably reflecting the critical (but ill-defined) roles of different B-cell and plasma cell populations in autoantibody production. Future studies during clinical trials of these agents are needed to define which B-cell and autoantibody populations are affected (or ought to be), and to discover informative biomarkers of clinical response that can be used to advance this therapeutic approach.

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Figure 1: The serial antibody profile of a patient with SLE in relation to therapy and disease activity.
Figure 2: Generation and categories of Ig-secreting cells.

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Acknowledgements

The authors' research activities are supported by a Veterans Administration Merit Review grant and NIH grants AI083923, AI082302 and T32-AI07217-28. P. E. Lipsky and A. C. Grammer were formerly in the autoimmunity branch of the Intramural Research Program, NIAMS, NIH, Bethseda, MD, USA.

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Authors and Affiliations

  1. Department of Medicine and Immunology, Medical Research Service, Durham VA Hospital, 151G Durham VAMC, 508 Fulton Street, Durham, 27705, NC, USA

    David S. Pisetsky

  2. Division of Rheumatology and Immunology, Duke University Medical Center, DUMC 2918, Durham, 27710, NC, USA

    Tony C. Ning

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  1. David S. Pisetsky
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  2. Amrie C. Grammer
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  3. Tony C. Ning
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  4. Peter E. Lipsky
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All authors contributed equally to all aspects of the preparation of this manuscript.

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Correspondence to David S. Pisetsky.

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Pisetsky, D., Grammer, A., Ning, T. et al. Are autoantibodies the targets of B-cell-directed therapy?. Nat Rev Rheumatol 7, 551–556 (2011). https://doi.org/10.1038/nrrheum.2011.108

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