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Disparity in Peripheral and Renal B-cell Depletion with Rituximab in Systemic Lupus Erythematosus: an Opportunity for Obinutuzumab?

Reddy, VR; Pepper, RJ; Shah, K; Cambridge, G; Henderson, SR; Klein, C; Kell, L; ... Leandro, MJ; + view all (2021) Disparity in Peripheral and Renal B-cell Depletion with Rituximab in Systemic Lupus Erythematosus: an Opportunity for Obinutuzumab? Rheumatology (Oxford) , Article keab827. 10.1093/rheumatology/keab827. (In press). Green open access

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Abstract

OBJECTIVES: To investigate key factors that may contribute to the variability of rituximab-mediated peripheral and renal B cell depletion (BCD) in Systemic Lupus Erythematosus (SLE). METHODS: We analysed: 1) CD19+ B cell counts in patients with SLE before and one, two, three and six months after treatment with rituximab, comparing them with Rheumatoid Arthritis (RA) patients; 2) the presence of B cells in renal biopsies after rituximab therapy; 3) whether the duration of BCD correlated with patient demographics and B cell expression of CD20 and FcγRIIb; and 4) the effect of BAFF on the efficiency of rituximab and obinutuzumab at inducing BCD in whole blood assays, in vitro. RESULTS: In SLE (n = 71), the duration of BCD was shorter compared with RA (n = 27). B cells were detectable in renal biopsy samples (n = 6) after treatment with rituximab in all patients with poor response whilst peripheral blood B cells remained low or undetectable in the same patients. There were no significant relationships between peripheral BCD and patient age, disease duration, serum C3 levels or the level of expression of B cell surface proteins CD20 and FcγRIIb. Obinutuzumab was more efficient than rituximab at inducing BCD in whole blood assays, regardless of excess BAFF. CONCLUSIONS: BCD in SLE is less efficient than in RA. Renal B cell presence following rituximab treatment was associated with poor outcomes. No significant relationships between any measured B cell related, clinical or laboratory parameters and the efficiency of BCD by rituximab was found. Obinutuzumab was superior to rituximab at inducing BCD.

Type: Article
Title: Disparity in Peripheral and Renal B-cell Depletion with Rituximab in Systemic Lupus Erythematosus: an Opportunity for Obinutuzumab?
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/keab827
Publisher version: https://doi.org/10.1093/rheumatology/keab827
Language: English
Additional information: © The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: B-cell depletion, lupus nephritis and Obinutuzumab, rituximab, systemic lupus erythematosus
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/10138880
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