Analysis of Synovial Tissue Macrophages: A Way to Predict RA Treatment Response?

Jul 10, 2024

Photo Credit: Pikovit44

Multimodal analysis of synovial tissue may identify patients with rheumatoid arthritis who subsequently respond to treatment with DMARDs.

A study in treatment-naïve patients with rheumatoid arthritis (RA) showed that multimodal analysis of synovial tissue might be able to identify patients who subsequently respond to treatment with conventional disease-modifying antirheumatic drugs (cDMARDs). Particularly, the ST macrophage population MerTKposCD206pos was an independent factor associated with achieving remission at 6 months.

As Simone Perniola, MD, pointed out, there is an unmet medical need to identify biomarkers predictive of treatment response in treatment-naïve patients with RA. Synovial tissue inflammation seen in RA reveals a high degree of heterogeneity of synovial tissue macrophages, which may be a factor in people’s response to treatments. Thus, Dr. Perniola and his team assessed the power of multimodal analysis of STM populations to identify predictive biomarkers of treatment response.

Enrolled were 373 treatment-naïve participants with RA who received an ultrasound-guided synovial tissue biopsy at first medical evaluation. The synovitis degree and synovial pathotype were then determined using immunohistochemistry for each participant. A subset of 45 samples underwent additional synovial tissue macrophage phenotyping and profiling to measure the abundance of distinct macrophage populations. Further, the transcriptomic profile of CD68-positive cells in distinct regions of interest within the synovial tissue was determined using spatial technology. After entry into the study, all participants were managed with a treat-to-target strategy.

Participants who reached disease remission at 6 months had a lower total Krenn Synovitis Score (KSS) at baseline compared with those who did not achieve this outcome (P<0.001). However, baseline KSS alone had limited predictive power, highlighting the need for a multimodal analysis.

Participants with a lymphomyeloid or diffuse myeloid pathotype had a lower response to cDMARDs (36.1% and 44.7%) compared with participants with a pauci-immune pathotype (59.1%; P= .001 and P=0.042, respectively).

Flow cytometry analysis revealed that those with lympho-myeloid or diffuse-myeloid pathotypes showed comparable enrichment of 2 distinct STM populations (namely MerTKposCD206pos and MerTKnegCD206neg), while participants with the pauci-immune pathotype showed a predominance of MerTKposCD206pos. Notably, enrichment of MerTKpos synovial tissue macrophages greater than 44.3% from baseline was an independent factor associated with achieving remission at 6 months (odds ratio 24.5; P<0.001).

According to this data, multimodal analysis of synovitis can differentiate patients with RA who are likely to respond to first-line cDMARDs from those who will not, supporting its utility as a predictive tool in clinical practice.