El‐Sherbiny, Y.M. ORCID: 0000-0003-4791-3475, Yusof, M.Y.M., Psarras, A., Hensor, E.M.A., Kabba, K.Z., Dutton, K., Mohamed, A.A.A., Elewaut, D., McGonagle, D., Tooze, R., Doody, G., Wittmann, M., Emery, P. and Vital, E.M., 2020. B cell tetherin: a flow‐cytometric cell‐specific assay for response to Type‐I interferon predicts clinical features and flares in SLE. Arthritis & Rheumatology, 72 (5), pp. 769-779. ISSN 2326-5191
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Abstract
Objective: Type I interferon (IFN-I) responses are broadly associated with autoimmune disease including SLE. Given the cardinal role of autoantibodies in SLE, we investigated whether a B cell-specific IFN assay might correlate with SLE activity.
Methods: B cells and PBMCs were stimulated with IFN-I and IFN-II. Gene expression was scrutinized for pathway-related membrane protein expression. A flow-cytometric assay for tetherin (CD317), an IFN-induced protein ubiquitously expressed on leucocytes, was validated in vitro then clinically against SLE diagnosis, plasmablast expansion, and BILAG-2004 score in a discovery cohort (156 SLE; 30 RA; 22 healthy controls). A second longitudinal validation cohort of 80 patients was also evaluated for SLE flare prediction.
Results: In vitro, a close cell-specific and dose-responsive relationship between IFN-I responsive genes and cell surface tetherin in all immune subsets existed. Tetherin expression on multiple cell subsets was selectively responsive to stimulation with IFN-I compared to IFN-II and -III. In patient samples from the discovery cohort memory B-cell tetherin was best associated with diagnosis (SLE/HC: effect size=0.11, p=0.003; SLE/RA: effect size=0.17, p
Item Type: | Journal article | ||||||
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Alternative Title: | B-Cell tetherin predicts SLE disease activity [running head] | ||||||
Publication Title: | Arthritis & Rheumatology | ||||||
Creators: | El‐Sherbiny, Y.M., Yusof, M.Y.M., Psarras, A., Hensor, E.M.A., Kabba, K.Z., Dutton, K., Mohamed, A.A.A., Elewaut, D., McGonagle, D., Tooze, R., Doody, G., Wittmann, M., Emery, P. and Vital, E.M. | ||||||
Publisher: | Wiley | ||||||
Date: | May 2020 | ||||||
Volume: | 72 | ||||||
Number: | 5 | ||||||
ISSN: | 2326-5191 | ||||||
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Divisions: | Schools > School of Science and Technology | ||||||
Record created by: | Linda Sullivan | ||||||
Date Added: | 02 Jan 2020 12:37 | ||||||
Last Modified: | 31 May 2021 15:07 | ||||||
URI: | https://irep.ntu.ac.uk/id/eprint/38914 |
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