Which blood immune-cell and gene-expression patterns are associated with more active rheumatoid arthritis?

Details

Rheumatoid arthritis (RA) management aims toward remission or low disease activity.

In this observational single-cell profiling study, researchers conducted single-cell RNA sequencing (scRNA-Seq) of peripheral blood mononuclear cells (PBMCs) from 36 individuals: 18 patients with RA and 18 controls matched for age, sex, race, and ethnicity. The aim was to identify disease-relevant cell subsets and cell type-specific signatures associated with disease activity.

The analysis identified 18 distinct PBMC subsets, including an interferon (IFN)-activated monocyte subset overexpressing IFN-induced transmembrane 3 (IFITM3).

CD4+ T effector memory cells were increased in patients with moderate-high disease activity, defined as DAS28-CRP ≥ 3.2. Nonclassical monocytes were decreased in patients with low disease activity or remission, defined as DAS28-CRP < 3.2.

Pseudobulk analysis by cell type identified 168 differentially expressed genes between RA patients and matched controls. Findings included downregulation of proinflammatory genes in the γδ T cell subset and alterations in genes associated with RA predisposition in the IFN-activated subset and nonclassical monocytes.

A gene signature associated with moderate-high disease activity showed upregulation of proinflammatory genes such as TNF, JUN, EGR1, IFIT2, MAFB, and G0S2, and downregulation of genes including HLA-DQB1, HLA-DRB5, and TNFSF13B.

Cell-cell communication analysis revealed upregulation of signaling pathways, including VISTA, in both moderate-high disease activity and remission-low disease activity contexts.

The researchers concluded that these findings provide insights into systemic cellular and molecular mechanisms underlying RA disease activity.