PLoS ONE 2021;16(1):e0244187This analysis provides evidence that immune cell signalling pathways are important in RA. There were consistent differences between RA patients and healthy controls in IFNα, IL-6, IL-10 and GM-CSF+ IL-2 induced JAK/STAT signalling in multiple immune cell subsets.We know that RA is characterised by dysregulation of immune responses, but the exact cause is unknown. Recently, single-cell transcriptomics and mass cytometry confirmed the critical role of activated immune cells and fibroblasts, increased cytokine expression, and cell signalling pathways in the synovitis that defines RA.This analysis used single cell network profiling to study 42 signalling nodes, chosen for their reported central roles in RA pathobiology, in 21 immune cell subsets in peripheral blood mononuclear cells (PBMC) from 194 patients with longstanding RA (including 98 patients before and after treatment), and 41 healthy controls (HC). Four cytokine induced JAK/STAT signalling pathways (IFNα, IL-6, IL-10 and GM-CSF+ IL-2) were chosen and analysed in multiple immune cell subsets. The findings may lead to the development of cellular biomarkers to assess the underpinnings of successful treatment response, thus improving quality of life and cost-effectiveness of RA patient management.