Dendritic Cells Profile in Inflamed Colonic Mucosa Predicts Response to Tumor Necrosis Factor Alpha Inhibitors in Inflammatory Bowel Disease
Background: Dendritic cells play a crucial role in the control of inflammation and immune tolerance in the gut. We aimed to investigate the effects of tumor necrosis factor-alpha inhibitors (TNFa) inhibitors on intestinal dendritic cells of patients with inflammatory bowel disease and their potential role in predicting response to treatment.
Methods: Intestinal biopsies were obtained from 30 patients with inflammatory bowel disease (16 Crohn's disease and 14 ulcerative colitis patients) before and after the treatment with TNFa inhibitors (infliximab 13 patients, adalimumab 17 patients). The proportions of lamina propria dendritic cells phenotypes were analyzed using flow cytometry. Disease activity was endoscopically assessed at baseline and after induction treatment.
Results: At baseline, the proportion of conventional dendritic cells was higher in inflamed (7.8%) compared to uninflamed mucosa (4.5%) (p = 0.003) and the proportion of CD103+ dendritic cells was lower in inflamed (47.1%) versus uninflamed mucosa (57.3%) (p = 0.03). After 12 weeks of treatment, the proportion of conventional dendritic cells in inflamed mucosa decreased from 7.8% to 4.5% (p = 0.014), whereas the proportion of CD103+dendritic cells remained unchanged. 18 out of 30 (60%) patients responded to treatment at week 12. Responders had significantly higher proportion of conventional dendritic cells (9.16% vs 4.4%, p < 0.01) with higher expression of HLA-DR (MFI 12152 vs 8837, p = 0.038) in inflamed mucosa before treatment compared to non-responders.
Conclusions: The proportion of conventional dendritic cells above 7% in inflamed inflammatory bowel disease mucosa before treatment predicts endoscopic response to TNFa inhibitors.
Keywords: Inflammatory bowel disease, dendritic cells, tumor necrosis factor-alpha inhibitors, colon cancer