Dotlacil Vojtech, Coufal Stepan, Lerchova Tereza, Zarubova Kristyna, Kucerova Barbora, Tlaskalova-Hogenova Helena, Kverka Miloslav, Skaba Richard, Bronsky Jiri, Hradsky Ondrej, Rygl Michal
Department of Paediatric Surgery, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.
Laboratory of Cellular and Molecular Immunology, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic.
Sci Rep. 2025 Jan 7;15(1):1138. doi: 10.1038/s41598-024-83858-7.
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.
本研究旨在探讨克罗恩病（CD）患儿肠道组织中抗肿瘤坏死因子α（抗TNF）、抗TNF抗体及细胞因子的相关影响因素。在一项针对2020年6月至2023年1月期间接受回盲部切除术或结肠镜检查的CD患者的前瞻性探索性研究中，我们分析了肠道活检组织中抗TNF、抗TNF抗体及细胞因子（TNF-α、IL-17、IL-1β、IFN-γ）的水平。采用了针对潜在混杂因素进行调整的混合效应回归模型。分析了27例CD患者（18例女性，占66.7%）的数据。14例（52%）接受阿达木单抗（ADA）治疗，13例接受英夫利昔单抗（IFX）治疗，中位治疗时长为17（四分位间距4.5 - 41.5）个月。与非炎症组织相比，在宏观炎症组织中发现游离抗TNF水平更高（β = 3.42，95%置信区间1.05 - 6.10）。血清和组织抗TNF水平之间未发现显著关联（β = -0.06，95%置信区间-0.70 - 0.58）。接受抗TNF治疗时间较长的患者IL-17水平升高（β = 0.19，95%置信区间0.05 - 0.33），与病程和年龄无关。IFN-γ水平与随访时长和抗TNF治疗时长均相关。我们的研究表明炎症组织中游离药物水平显著更高。长期抗TNF治疗与IL-17水平升高有关，提示可能对细胞因子反应途径有影响。我们未观察到血清和组织抗TNF水平之间存在关联。
