Background and objectives Type I interferons (IFN-I) have diverse effects on immune cell populations in SLE, Measuring IFN-I using whole blood interferon-stimulated gene (ISG) expression does not completely explain clinical features of SLE. Objective: develop a cell-specific assay using a surface protein encoded by an ISG (BST2). This would allow convenient analysis of IFN response in individual populations to improve immunophenotyping of SLE patients.
Materials and methods PBMCs from 133 SLE patientsand 19 healthy controls (HC) were analysed by flow cytometry for cell surface BST2 protein on each immune cell subset. Cells were FACS-sorted into naïve and memory B-cells, plasmablasts, CD3+ T-cells, NK-cells and monocytes in 12 SLE patients and 16 healthy controls. Expression of BST2, as well as 32 other ISGs, were measured using qPCR.
Results Analysis of sorted cells confirmed that surface BST2 is a valid cell-specific IFN assay. BST2 expression correlated with BST2 surface protein within each immune subset: naïve B-cells (r = 0.63, p = 0.009); memory B-cells (r = 0.78, p < 0.001); plasmablasts (r = 0.58, p = 0.018);NK cells (0.63, p = 0.008);T-cells (r = 0.61, p = 0.012); monocytes (r = 0.47, p = 0.064).
We next used surface BST2 to compare IFN activity of each subset with clinical features in 133 patients. A significant correlation between the PBMC 33-gene IFN score and surface BST2 for each cell subset (all p < 0.001) confirmed validity of BST2 biomarker in this larger population as a measure of overall IFN status.
BST2 was significantly higher in SLE than HC on naïve and memory B-cells (p = 0.004, p = 0.003), plasmablasts (p = 0.047), T cells (p = 0.043), but not different on monocytes (p = 0.406).
Association of disease activity (total BILAG) with BST2 on naïve and memory B-cells (Tau-a = 0.23 and 0.22 respectively) was substantive and approximately twice as strong as monocytes and T-cells (Tau-a = 0.12 and 0.14). A similar pattern was seen for anti-dsDNA titre, with no association with monocyte BST-2 (Tau-a = 0.07) but a substantive association for memory B cell BST-2 (Tau-a = 0.18).
Conclusion IFN-I response differs in cell subsets. This can be measured in a fast, cost-effective, convenient assay using flow cytometric analysis of surface BST2. Our results show that IFN activity measured on B cells is more clinically relevant than on other cell populations.
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