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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月7日

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  • Vojtech Dotlacil,
  • Stepan Coufal,
  • Tereza Lerchova,
  • Kristyna Zarubova,
  • Barbora Kucerova,
  • Helena Tlaskalova-Hogenova,
  • Miloslav Kverka,
  • Richard Skaba,
  • Jiri Bronsky,
  • Ondrej Hradsky,
  • Michal Rygl

摘要

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.