A unique subset of macrophages in the synovial tissue has been identified in patients with rheumatoid arthritis, showing early signs before clinical onset, according to a recent study. 

In the study, published in Science Advances, researchers examined macrophage populations within the synovial tissue of patients with rheumatoid arthritis (RA), patients at risk for RA, and healthy controls. They used flow cytometry, RNA sequencing, and metabolic analysis to identify distinct transcriptional profiles of these macrophages, showing that they primarily rely on oxidative phosphorylation for energy. 

RA synovial tissue demonstrated a higher frequency and median fluorescence intensity (MFI) of pan macrophage markers CD68 and CD64 compared with synovial fluid mononuclear cells (SFMC), indicating a greater presence of macrophages in the synovial tissue (P < .05). The researchers identified a macrophage subset expressing CD40, CD206, and CD163 in the inflamed RA synovium, with its frequency correlating with RA disease activity scores (DAS28) and predicting treatment response.

Single-cell RNA sequencing identified nine distinct macrophage clusters, with IL^-1B⁺CCL20⁺ and SPP1⁺MT2A⁺ clusters predominant in the RA synovium and characterized by high CD40 gene expression. These macrophage signatures were identified in synovial tissue from patients at risk of developing RA, indicating that the disruption of macrophage homeostasis, particularly with the expression of CD40, could occur early in RA pathogenesis.

The frequency of CD206⁺CD163⁺CD40⁺ macrophages in RA synovial tissue was significantly correlated with disease activity, as indicated by a correlation coefficient of r = 0.6 with DAS28 scores (P < .01).

Follow-up clinical data demonstrated that patients with RA who had higher baseline levels of CD206⁺CD163⁺CD40⁺ macrophages had a greater response to treatment at a 1-year follow-up, as indicated by a strong inverse correlation between the baseline expression of this macrophage subset and change in DAS28 score (r = –0.75, P < .01).

FLIM analysis of sorted RA synovial tissue macrophages revealed that CD206⁺CD163⁺ macrophages exhibited a metabolic preference for oxidative phosphorylation, significantly differing from CD206⁻CD163⁻− macrophages as demonstrated by a higher optical redox ratio (P < .05).

In the healthy synovium, the main macrophage population consisted of CD206⁺CD163⁺ cells, which had similar expression levels to those in the RA synovium. However, unlike in RA, these macrophages did not coexpress CD40, as demonstrated by flow cytometry and related quantification (P < .05).

Full disclosures can be found in the published study.