DOI: 10.1101/19011460Feb 3, 2020Paper

Distinct single cell gene expression in peripheral blood monocytes correlates with treatment response groups defined by type I interferon in rheumatoid arthritis

MedRxiv : the Preprint Server for Health Sciences
Theresa Wampler MuskardinTimothy B Niewold

Abstract

Objective: Previously, we have shown that the ratio of IFN{beta}/ activity can predict response to tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis (RA). In this study, our objective was to better understand the impact of this type I IFN ratio in monocytes from RA patients. Methods: We compared single cell gene expression in purified classical (CL) and non-classical (NC) monocytes from RA patients. Patients with high vs. low serum IFN{beta}/ ratio were compared to each other, as determined by functional type I IFN assay. Results: We found large differences in monocyte gene expression between patients with different IFN{beta}/ ratios, which was apparent in principal component analysis. Cluster analysis also documented strong differences between these response groups. In CL monocytes, decreased expression of JAK1 and IFI27 were strongly associated with the non-response low IFN{beta}/ ratio. In NC monocytes, increased expression of HLADRB1, TNFA, PDL1, TGFB, and others were associated with the non-response IFN ratio. Interestingly, JAK1 expression was absent in all monocytes from some patients. This pattern was strongly associated with the non-response type I IFN ratio, suggesting a major biological difference betwe...Continue Reading

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