Aims: Understanding of the molecular mechanisms of anti-TNFα therapy non-response and reliable biomarkers are essential for personalized medicine in Crohn's disease (CD) patients. Using RNA-seq data adjusted for deconvoluted fractions of peripheral blood cells, we recently described MMD gene, coding for a monocyte to macrophage differentiation factor, as a biomarker of adalimumab (anti-TNFα) therapy response in CD. The results also suggest that cell subtype-specific biomarkers may be superior to those measured in bulk peripheral blood. Here, we used functional cell model to further investigate the role of the monocyte to macrophage differentiation in adalimumab treatment response and evaluate monocyte/macrophage specific expression of the inflammatory cytokines as potential biomarkers for (non)response to adalimumab in CD patients.
Main methods: The peripheral monocytes of CD patients responsive and non-responsive to adalimumab were isolated, differentiated into macrophages, and exposed to inflammation and concurrent adalimumab therapy in vitro. The results were correlated to the clinical response of the donor patients.
Key findings: Correlation is shown of the expression of two macrophage differentiation related genes- CD68 and MMD, with the expression of the inflammatory cytokines TNF, IL1B, IL6 and CXCL8. Monocytes and in vitro differentiated macrophages of adalimumab non-responders express more inflammatory cytokines than those of responders. The biggest difference was in the IL1B expression. Additionally, IL1B expression in the in vitro differentiated macrophages of CD patients correlates negatively with their clinical response to adalimumab.
Significance: We propose the IL1B expression in the macrophages as a possible biomarker for adalimumab response in CD patients.
Keywords: Anti-TNFα therapy; Crohn's disease; In vitro inflammation; In vitro monocyte to macrophage differentiation; Inflammatory cytokines; Personalized medicine.
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