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FRI0375 Flow-Based Cell-Specific Interferon Signature as a Biomarker in Systemic Lupus Erythematosus

Background Type I interferons (IFNs) have been confirmed to play a pivotal role in the pathogenesis of Systemic lupus erythematosus (SLE) and Rheumatoid arthritis (RA). IFN activity is usually monitored using a whole blood signature of IFN responsive genes. However; (i) these signatures do not correlate with disease activity, (ii) they also do not predict response to anti-IFN therapy. This may be because IFN response varies in different cell populations whose frequency varies in different disease states. We therefore sought a cell specific IFN signature using surface expression of the IFN response protein, Siglec-1 (sialoadhesin, CD169), which represents type I IFN activity on monocytes. B cells are involved in both diseases and have been target of therapy by different biologics. Changes in B cell subsets (esp. plasmablast (PB) expansion) are associated with disease activity. Hence, we investigated the correlation of different B cell subsets with the level of Siglec-1 in RA and SLE patients. Objectives To study the use of a flow cytometry cell specific assay for interferon signature in SLE. Methods Peripheral blood was collected from 27 SLE patients, 18 RA patients and 5 healthy controls (HC) and was analyzed for the level of Siglec-1 (CD169) expression on monocytes as well as for the numbers of naïve, memory and PB B cell subsets using multi-parameter flow cytometry using panels including: CD19, CD27, CD38, CD3, CD4, CD8, CD16, CD14, CD56, CD64, CD69 and CD169. Disease activity was measured by BILAG-2004 for SLE patients and DAS-28 for RA patients. Results Siglec-1 was found significantly higher in SLE and RA than in HC (p=0.03) (ANOVA test). However, no significant difference was found between RA and SLE Siglec-1 expression. In SLE patients, Siglec-1 was found significantly higher in patients with high BILAG score (n=6) than those with low BILAG (n=17) (p=0.0002) (Mann Whitney test). Moreover, Siglec-1 was significantly correlated with levels of autoantibodies in SLE patients (P=0.0175, r=0.634) (Spearman); the number of autoantibody positivity was associated with higher Siglec-1 expression on monocytes. Although BILAG score was significantly correlated with percentage of PB in SLE patients' blood (p=0.008, r=0.681) (Spearman R), we found no significant correlation between PB numbers or other cell subsets and Siglec-1 levels on monocytes. Interestingly, CD64 on monocytes was also upregulated in SLE and significantly correlated with Siglec-1. Conclusions Monocyte Siglec-1 expression level as a measure of type I IFN activity were correlated with the disease activity and the number of autoantibody positivity in SLE. However, it does not explain the characteristic changes in B cell differentiation. Moreover, it does not act as a disease specific marker since it was invariably high in the active state of both diseases. Disclosure of Interest None declared