Macrophage profiling in synovial tissue predicts treatment response in RA

A recent study in treatment-naïve patients with rheumatoid arthritis (RA) revealed that profiling synovial tissue macrophages (STMs) could identify those likely to achieve remission. The presence of MerTKposCD206pos macrophages was strongly linked to successful treatment outcomes with conventional DMARDs, offering a new avenue for personalised therapy.

Previous research has shown that STM subsets regulate inflammation and remission in RA [1]. STMs reveal a high rate of heterogeneity, which may be a factor in people’s response to treatments. As Dr Simone Perniola (Policlinico Universitario A. Gemelli IRCS, Italy) pointed out, there is a need to identify biomarkers that can predict treatment response in treatment-naïve patients with RA. Thus, Dr Perniola and his team assessed the power of multimodal analysis of STM populations to identify predictive biomarkers of treatment response [2].

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 STM 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 study entry, 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=0.0006). However, baseline KSS alone had limited predictive power, highlighting the need for a multimodal analysis. Participants with lympho-myeloid or diffuse-myeloid pathotype had a lower response to conventional DMARDs (36.1% and 44.7%) compared with participants with a pauci-immune pathotype (59.1%; P=0.001 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, baseline enrichment of MerTKpos STMs greater than 44.3% was shown to be an independent factor associated with achieving remission at 6 months (odds ratio 24.5; P<0.0001).

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

1. Alivernini S, et al. Nat Med 2020;26:1295-1306.
2. Perniola S. Multi-modal analysis of synovial tissue macrophages informs on treatment response in naive to treatment rheumatoid arthritis. OP0062, EULAR 2024 Congress, 12–15 June, Vienna, Austria.

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Posted on 29 July 2024