Using mass cytometry to probe the STAT signaling landscape in circulating immune cells in Rheumatoid Arthritis uncovers signaling dysregulation and correlation with disease activity

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Source: Frontiers Medicine

Original: https://www.frontiersin.org/articles/10.3389/fmed.2025.1622537...

Published: 2025-12-09T00:00:00Z

The study used mass cytometry (CyTOF) to analyze the phosphorylated forms of STAT signaling proteins in circulating immune cells in 21 patients with rheumatoid arthritis (RA) and 10 healthy controls. They identified 34 immune subpopulations and measured the levels of pSTAT1, pSTAT3, pSTAT4, pSTAT5 and pSTAT6. Increased levels of pSTAT5 occurred in some CD4 T cells and correlated with disease activity as measured by DAS28-ESR and DAS28-CRP scores. pSTAT1 was increased in CD4 T cells, CD8 T cells, NK cells, monocytes and dendritic cells. Conversely, pSTAT6 was lower in some CD4 T cells including regulatory T cells and negatively correlated with CDAI. The frequency of CD4 T effector memory cells with chemokine receptors CCR2 and CCR5 was lower in RA patients. These phosphorylation patterns are associated with immune dysregulation and correlate with the level of RA activity. Analysis of the phosphorylation of STAT proteins can help to better understand the pathology of RA and serve as a marker for monitoring the disease and response to treatment. Fixation of blood close to collection allowed to maintain phosphorylation patterns close to in vivo conditions.