Zapata-Cobo Paula, Salvador-Martín Sara, Gil-Manso Sergio, Rodríguez-Belvís Marta Velasco, Palomino Laura M, Moreno-Álvarez Ana, Pérez-Moneo Begoña, García-Romero Ruth, Fobelo María J, García-Tirado Diana, Sánchez César, Pujol-Muncunill Gemma, Segarra Oscar, Montraveta Montserrat, Magallares Lorena, Correa-Rocha Rafael, Sanjurjo-Sáez María, Pion Marjorie, López-Fernández Luis A
Servicio de Farmacia, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain.
Laboratory of Immuno-Regulation, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, 28007 Madrid, Spain.
Int J Mol Sci. 2025 Apr 2;26(7):3323. doi: 10.3390/ijms26073323.
Failure of anti-TNF therapy is a real concern in children with inflammatory bowel disease (IBD) owing to the limited therapeutic arsenal. Anti-TNF drugs modulate the immune response, a key driver of chronic inflammation in IBD. Accordingly, we analyzed changes in the frequency of T-lymphocyte and cytokine levels after 6 weeks of treatment to identify potential biomarkers of response to anti-TNF drugs. We recruited 77 patients under 18 years of age diagnosed with IBD and treated with an anti-TNF drug. Using flow cytometry and multiplex ELISA, we analyzed 31 T-lymphocyte populations and four cytokines. We identified changes in 10 populations of T lymphocytes after 6 weeks of treatment. Naïve Tregs were associated with a primary response to anti-TNF drugs, while activated Tregs were associated with long-term response. Serum INF-γ levels were decreased after anti-TNF treatment in children with Crohn's disease (CD), but not in those with ulcerative colitis (UC). The memory CD8+ Type 2 Cytotoxic T (Tc2) subset increased in non-responders with CD and the CD4+ memory Th17 cells increased in non-responders with UC. These findings could help us to understand the cellular regulation of anti-TNF therapy, to identify children at a higher risk of treatment failure, and, potentially, to develop more personalized therapeutic strategies.
由于治疗手段有限，抗TNF治疗失败是炎症性肠病（IBD）患儿面临的一个实际问题。抗TNF药物可调节免疫反应，而免疫反应是IBD慢性炎症的关键驱动因素。因此，我们分析了治疗6周后T淋巴细胞频率和细胞因子水平的变化，以确定抗TNF药物反应的潜在生物标志物。我们招募了77名18岁以下诊断为IBD并接受抗TNF药物治疗的患者。使用流式细胞术和多重ELISA，我们分析了31个T淋巴细胞群体和四种细胞因子。我们发现治疗6周后10个T淋巴细胞群体发生了变化。初始调节性T细胞（Tregs）与抗TNF药物的初始反应相关，而活化的Tregs与长期反应相关。克罗恩病（CD）患儿抗TNF治疗后血清干扰素-γ（INF-γ）水平降低，但溃疡性结肠炎（UC）患儿未降低。无反应的CD患儿中记忆性CD8 + 2型细胞毒性T细胞（Tc2）亚群增加，无反应的UC患儿中CD4 + 记忆性辅助性T细胞17（Th17）增加。这些发现有助于我们了解抗TNF治疗的细胞调节机制，识别治疗失败风险较高的儿童，并有可能制定更个性化的治疗策略。
