Date: Monday, November 6, 2017
Session Type: ACR Concurrent Abstract Session
Session Time: 4:30PM-6:00PM
SLE is an IFN-I-mediated disease with dysregulated handling of self-nuclear antigens triggering anti-viral immune mechanisms. The level of IFN-I activity appears to stratify for disease severity and therapy response but existing studies using IFN-stimulated gene (ISG) expression signatures weakly correlates with clinical features. ISG expression influenced by cellular composition of sample and individual cell responses. CD317/Tetherin is a cell surface protein encoded by the interferon-stimulated gene BST2. So we aimed to develop a fast, convenient assay to measure cell-specific IFN-I suitable for analysis of large cohorts of patients using flow cytometry correlates with disease activity and predicts clinical flare.
We developed a flow cytometric assay for cell-specific IFN-I response using tetherin, as well as ISG gene expression score derived from 18 well known. FACS sorting was used to evaluate cell-specific interferon response by both assays. IFN-I biomarkers were then evaluated against diagnosis, disease activity in a discovery cohort of 156 SLE patients with 30 ACPA+ANA- RA (DAS28>3.2) and 22 healthy controls. A longitudinal validation cohort of 80 patients with monitoring of tetherin in an independent routine diagnostic laboratory was recruited to confirm findings and test prediction of flares.
In vitro, ISG expression score predominantly reflected monocyte signal and many ISGs responded to both IFN-a and IFN-g. Flow cytometric analysis of tetherin (BST2) accurately determined cell-specific response to IFN-I in a dose-responsive manner and was more selective for IFN-I.
In the discovery cohort, B cell tetherin was associated with diagnosis and clinical disease activity equally or more closely than gene expression score or monocyte tetherin. Memory B cell tetherin was increased with renal (p=0.005) or haematological (p=0.005) activity with no differences in ISG score for these domains (p=0.152, p=0.989 respectively). The validation cohort confirmed the relationship between B cell tetherin and disease activity
and also, showed that higher B cell tetherin predicted increased risk of future clinical flares. (Fig 2)
The B cell response to IFN-I predicts clinical features of SLE, and tetherin provides a convenient, validated method to analyse this pathway in routine clinical practice. Tetherin is also a tool for future research in cell-specific IFN-I response in a broad spectrum of other diseases.
To cite this abstract in AMA style:El-Sherbiny YM, Md Yusof MY, Psarras A, Hensor EMA, Kabba K, Mohamed A, Wittmann M, Emery P, Vital EM. A Novel Type I Interferon Biomarker on B Cell Predicts with Disease Activity in SLE and Can be Measured By Cell Surface Tetherin (CD317) [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/a-novel-type-i-interferon-biomarker-on-b-cell-predicts-with-disease-activity-in-sle-and-can-be-measured-by-cell-surface-tetherin-cd317/. Accessed July 8, 2020.
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