B cell tetherin: a flow‐cytometric cell‐specific assay for response to Type‐I interferon predicts clinical features and flares in SLE

El‐Sherbiny, YM ORCID: https://orcid.org/0000-0003-4791-3475, Yusof, MYM, Psarras, A, Hensor, EMA, Kabba, KZ, Dutton, K, Mohamed, AAA, Elewaut, D, McGonagle, D, Tooze, R, Doody, G, Wittmann, M, Emery, P and Vital, EM, 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
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
Identifiers:	Number Type 10.1002/art.41187 DOI 1253231 Other
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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