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The BAFFling effects of rituximab in lupus: danger ahead?

Ehrenstein, MR; Wing, C; (2016) The BAFFling effects of rituximab in lupus: danger ahead? Nature Reviews Rheumatology , 12 (6) pp. 367-372. 10.1038/nrrheum.2016.18. Green open access

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Abstract

Suboptimal trial design and concurrent therapies are thought to account for the unexpected failure of two clinical trials of rituximab in patients with systemic lupus erythematosus (SLE). However, in this Opinion article we propose an alternative explanation: that rituximab can trigger a sequence of events that exacerbates disease in some patients with SLE. Post-rituximab SLE flares that are characterized by high levels of antibodies to double-stranded DNA are associated with elevated circulating BAFF (B-cell-activating factor, also known as TNF ligand superfamily member 13B or BLyS) levels, and a high proportion of plasmablasts within the B-cell pool. BAFF not only perpetuates autoreactive B cells (including plasmablasts), particularly when B-cell numbers are low, but also stimulates T follicular helper (TFH) cells. Moreover, plasmablasts and TFH cells promote each others' formation. Thus, repeated rituximab infusions can result in a feedback loop characterized by ever-rising BAFF levels, surges in autoantibody production and worsening of disease. We argue that B-cell depletion should be swiftly followed by BAFF inhibition in patients with SLE.

Type: Article
Title: The BAFFling effects of rituximab in lupus: danger ahead?
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nrrheum.2016.18
Publisher version: http://dx.doi.org/10.1038/nrrheum.2016.18
Language: English
Additional information: Copyright © 2016 Macmillan Publishers Limited. All rights reserved. The published version of record [Ehrenstein, MR; Wing, C; (2016) The BAFFling effects of rituximab in lupus: danger ahead? Nature Reviews Rheumatology , 12 (6) pp. 367-372. 10.1038/nrrheum.2016.18] is available on the journal website at http://www.nature.com/nrrheum/journal/v12/n6/full/nrrheum.2016.18.html
Keywords: Molecular medicine; Systemic lupus erythematosus; Therapeutics
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/1481096
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