Fig. 1: Synovial AXL and MERTK have distinct molecular expression patterns in early untreated RA patients. | Nature Communications

Fig. 1: Synovial AXL and MERTK have distinct molecular expression patterns in early untreated RA patients.

From: Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis

Fig. 1

A Axl and MerTK gene expression (regularised-log normalised reads) in synovial tissue of early arthritis treatment-naive RA patients (n = 87) according to the histological pathotype defined as Pauci-Immune (P-I, in green), Diffuse-Myeloid (D-M, in red), and Lympho-Myeloid (L-M, in blue). Data are represented as mean ±SEM. p values indicated were calculated using the Kruskal–Wallis test with Dunn’s post hoc test. B Correlation between synovial AXL (top panels) and MERTK (bottom panels) gene expression and semi-quantitative scores (0–4) of B cells (CD20), T cells (CD3), plasma cells (CD138), and sublining macrophages (CD68SL). p values and r-coefficients were calculated using the two-tailed Pearson correlation test. C Regression model analysis with interaction term to estimate the correlation of AXL with MERTK expression in relation to clinical response to conventional synthetic Disease-Modifying-Anti-Rheumatic-Drugs. The clinical response was assessed by EULAR criteria with DAS28(CRP) after 6-months of treatment (good responders in light blue; moderate and non-responders in orange). p-interaction is not significant. The scatter plots show the regression line of the fitted negative binomial generalised mixed effects model with the error bars showing 95% confidence interval (fixed effects). D 2D polar plot of transcript modules containing AXL and MERTK in synovial tissue characterised by lympho-myeloid (L-M), diffuse-myeloid (D-M), and pauci-immune (P-I) pathotypes. Different colours show pairwise comparisons between the three pathotypes: upregulation in one group only (D-M: red, P-I: green and L-M: blue) or in two groups (D-M/P-I: yellow, L-M/P-I: light blue, L-M/D-M: purple). E, F Heatmaps showing the correlation between AXL and MERTK synovial transcript levels at baseline and cytokines and growth factors relevant to the inflammatory response (E) and clinical parameters (F). The red/blue scale represents the Spearman r coefficient, calculated using the two-tailed Spearman correlation test. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. CRP, C-Reactive Protein; ESR, erythrocyte sedimentation rate; DAS28 disease activity score 28; TJC/28, tender joints count (0-28); SJC/28, swollen joints count (0-28); VAS GH, Visual Analogue Scale General Health (0–100); HAQ health assessment questionnaire.

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