Fig. 5: AXL is modulated by IL-6 pathway inhibition. | Nature Communications

Fig. 5: AXL is modulated by IL-6 pathway inhibition.

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

Fig. 5

A, B Linear regression model analysis with interaction term to estimate the correlation of AXL with MERTK expression in relation to clinical response to tocilizumab (A) and rituximab (B) in anti-TNF inadequate responder RA patients (R4RA cohort, n = 133, including 65 tocilizumab-treated and 68 rituximab-treated patients). The clinical response was assessed by EULAR criteria with DAS28(CRP) after 16 weeks of treatment (good responders in light blue; moderate and non-responders in orange). p-interaction is significant (0.018) in the tocilizumab-treated patient group and not significant in the rituximab-treated patient group. 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). C, D AXL (C) and MERTK (D) normalised gene expression levels assessed at baseline and 16 weeks following tocilizumab (left panels, n = 15 matched samples) or rituximab (right panels, n = 29 matched samples) treatment. CDAI 50% improvement was used to assess the clinical response (responders in light blue, non-responders in orange). Statistical analysis was performed by negative binomial generalised mixed effects model. FDR: false discovery rate. Data are shown as mean ±95% confidence interval. E IL-6/AXL expression ratio in the synovial tissue of tocilizumab- (n = 15) or rituximab- (n = 29) treated patients. Data are represented as mean ±SEM. p values indicated were calculated using the two-tailed Wilcoxon test for paired data. F Pie chart showing the percentage of Axl or MerTK single positive, MerTK and Axl double-positive and negative synovial tissue of anti-TNF inadequate responder RA patients (R4RA cohort) at baseline pre- (n = 24) and post-treatment with either tocilizumab or rituximab (RTX-treated n = 3, TOC-treated n = 5) (left panels) and representative images of double immunofluorescence staining for Axl (red) and MerTK (yellow) (right panels). Scale bar = 50 μm.

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