RT Journal Article
SR Electronic
T1 B cell tetherin: a flow-cytometric cell-specific assay for response to Type-I interferon predicts clinical features and flares in SLE
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 554352
DO 10.1101/554352
A1 Yasser M. El-Sherbiny
A1 Md. Yuzaiful Md. Yusof
A1 Antonios Psarras
A1 Elizabeth M. A. Hensor
A1 Kumba Z. Kabba
A1 Katherine Dutton
A1 Alaa A.A. Mohamed
A1 Dirk Elewaut
A1 Dennis McGonagle
A1 Reuben Tooze
A1 Gina Doody
A1 Miriam Wittmann
A1 Paul Emery
A1 Edward M. Vital
YR 2019
UL http://biorxiv.org/content/early/2019/02/19/554352.abstract
AB 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 lineage 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 scrutinised 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 was selectively responsive to the IFN-I compared to IFN-II and -III. In 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<0.001); plasmablast numbers in rituximab-treated patients (Rho=0.38, p=0.047) and BILAG-2004. Association were equivalent or stronger than interferon score or monocyte tetherin. The validation cohort confirmed this relationship with memory B-cell tetherin predictive of future clinical flares (Hazard Ratio=2.29 (1.01–4.64), p=0.022).Conclusion Memory B cell surface tetherin, a reflection of cell-specific IFN response in a convenient flow cytometric assay, was associated with SLE diagnosis, disease activity and predicted flares better than other cell subsets or whole blood assays in independent validation cohorts.