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Abstract Number: 0787

MerTK Synovial Expression Correlates with Disease Activity and Treatment Response in Rheumatoid Arthritis Patients

Alessandra Nerviani1, Marie-Astrid Boutet1, Giulia Maria Ghirardi2, Gloria Lliso-Ribera2, Felice Rivellese1, Myles Lewis1, Michele Bombardieri2, Frances Humby2 and Costantino Pitzalis2, 1Centre for Experimental Medicine and Rheumatology, Queen Mary University of London, London, United Kingdom, 2Queen Mary University of London, London, United Kingdom

Meeting: ACR Convergence 2020

Keywords: macrophages, rheumatoid arthritis, Synovitis

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Session Information

Date: Saturday, November 7, 2020

Title: RA – Etiology & Pathogenesis Poster

Session Type: Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Despite valuable improvements in long-term clinical outcomes, a significant portion of rheumatoid arthritis (RA) patients still do not adequately respond to available treatments, and early prognostic biomarkers of response are missing. Single-cell transcriptomic studies on RA synovial tissue (ST) revealed that MerTK is highly expressed in “anti-inflammatory” macrophages [1]. Moreover, synovial macrophages isolated from RA patients in remission show a typical CD206+/MerTK+ signature [2]. Finally, monocyte-derived macrophages from RA patients treated with TNF-inhibitors (TNF-i) up-regulate MerTK on their surface.
In this study, we aim at i) assessing the modulation of synovial tissue MerTK+ macrophages upon treatment with conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs) and ii) evaluating the relationship between baseline MerTK synovial gene expression and future response to TNFi.

Methods: Patients with early (< 12 months) treatment-naïve RA (as per ACR/EULAR 2010 criteria) underwent a US-guided synovial biopsy of an inflamed peripheral joint at baseline and a second biopsy of the same joint six months after starting treatment with single or multiple csDMARDs. ST was collected and used for histology and RNA extraction. ST (n=15) was stained for CD68, MerTK and CD206 by immunofluorescence using a tyramide amplification signal system. The percentage of single- (MerTK+ or CD206+) and double-positive (CD206+MerTK+) CD68+ macrophages was quantified by digital image analysis (Image J). Gene expression analysis was performed on RNA sequences of 22 baseline ST-samples (treatment-naïve).

Results: Before treatment, the percentage of MerTK+CD206+ macrophages was significantly higher in RA patients with low (DAS28< 3.2) versus high (DAS28 >5.1) disease activity (24.5±20.1 versus 4.8±4.8, p< 0.05). No differences were detected in the relative number of MerTK+ or CD206+ or MerTK+CD206+ macrophages at baseline in relationship with the clinical response to csDMARDs at 6-months. Patients (n=5) achieving remission (DAS< 2.6) at 6-months significantly increased the number of MerTK+ macrophages from baseline in comparison with patients (n=5) who were still active post-treatment (23.6±23.8 to 55.5±15.4, p< 0.05 versus 18±15.6 to 30.4±11.17, p=ns). MerTK synovial gene expression at baseline (i.e., in newly diagnosed treatment-naïve RA patients) was significantly higher in patients who subsequently responded to TNFi (n=14, good/moderate EULAR) in comparison with those who did not respond (n=8) (p = 0.003).

Conclusion: Our whole-tissue expression data further corroborate the hypothesis that a selective expansion of the MerTK+ macrophage subset defines patients achieving remission. Moreover, the up-regulation of the MerTK gene at baseline in patients future responders to TNFi suggest that MerTK is involved in modulating synovial inflammatory responses and might be exploited as a therapeutic target in RA.


Disclosure: A. Nerviani, None; M. Boutet, None; G. Ghirardi, None; G. Lliso-Ribera, None; F. Rivellese, None; M. Lewis, None; M. Bombardieri, None; F. Humby, None; C. Pitzalis, None.

To cite this abstract in AMA style:

Nerviani A, Boutet M, Ghirardi G, Lliso-Ribera G, Rivellese F, Lewis M, Bombardieri M, Humby F, Pitzalis C. MerTK Synovial Expression Correlates with Disease Activity and Treatment Response in Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/mertk-synovial-expression-correlates-with-disease-activity-and-treatment-response-in-rheumatoid-arthritis-patients/. Accessed .
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