Intestinal tissue levels of anti-TNF alpha, antibodies, and cytokines in paediatric Crohn disease

Vojtech Dotlacil; Stepan Coufal; Tereza LerchovaKristyna ZarubovaBarbora Kucerova; Helena Tlaskalova-Hogenova; Miloslav Kverka; Richard SkabaJiri BronskyOndrej HradskyMichal Rygl | Scientific Reports | Jan 2025 | IF: 3,8 | doi

MUDr. Vojtěch Dotlačil, Department of Paediatrics Surgery, Second Faculty od Medicine and Motol University Hospital

MUDr. Vojtěch Dotlačil, Department of Paediatrics Surgery, Second Faculty od Medicine and Motol University Hospital


Abstract

The aim was to explore factors associated with intestinal tissue levels of anti-TNF alpha (anti-TNF), anti-TNF antibodies, and cytokines in pediatric patients with Crohn Disease (CD). In a prospective exploratory study of CD patients undergoing ileocecal resection or colonoscopy between 6/2020 and 1/2023, we analysed tissue levels of anti-TNF, anti-TNF antibodies, and cytokines (TNF-α, IL-17, IL-1β, IFN-γ) from intestinal biopsies. Mixed-effects regression models, adjusted for potential confounders, were used. Data from 27 CD patients (18 females, 66.7%) were analysed. Fourteen (52%) received adalimumab (ADA) and thirteen received infliximab (IFX), with a median therapy duration of 17 (IQR 4.5-41.5) months. Higher levels of free anti-TNF were found in macroscopically inflamed tissue compared to non-inflamed tissue (β = 3.42, 95% CI 1.05-6.10). No significant association was found between serum and tissue anti-TNF levels (β= -0.06, 95% CI - 0.70-0.58). Patients treated longer with anti-TNF had increased IL-17 levels (β = 0.19, 95% CI 0.05-0.33), independent of disease duration and age. IFN-γ levels were linked with both follow-up duration and anti-TNF length. Our study shows significantly higher free drug levels in inflamed tissue. Long-term anti-TNF treatment has been linked to increased IL-17 levels, suggesting a possible impact on the cytokine response pathway. We did not observe a relationship between serum and tissue anti-TNF levels.

Vytvořeno: 17. 1. 2025 / Upraveno: 17. 1. 2025 / Bc. Luděk Liška