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通过儿童克罗恩病治疗1年时的血清肿瘤坏死因子-α水平预测深度缓解

Prediction of deep remission through serum TNF-α level at 1 year of treatment in pediatric Crohn's disease.

作者信息

Kim Seon Young, Kwon Yiyoung, Kim Eun Sil, Kim Yoon Zi, Kim Hansol, Choe Yon Ho, Kim Mi Jin

机构信息

Department of Pediatrics, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.

Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Sci Rep. 2025 Apr 1;15(1):5770. doi: 10.1038/s41598-025-89578-w.

Abstract

A pilot study investigated the cytokine profile (IL-6, TNF-α, IL-17 A, and IL-10) at diagnosis, affecting infliximab (IFX) trough levels (TLs) in pediatric patients with Crohn's disease (CD). In this follow-up study, we evaluated the changes in cytokine level changes after Crohn's disease treatment. Cytokines were re-measured after 1 year of treatment. infliximab trough levels and total anti-infliximab antibodies were also measured in patients who had started infliximab treatment. In total, 29 patients followed up for a year after moderate to severe Crohn's disease diagnosis from June 2020 to June 2021 were enrolled. The mean concentrations of all cytokines at one year were significantly lower than those at the time of diagnosis. IL-6, IL-17 A, and IL-10 concentrations at 1 year maintained their correlation with each other observed at diagnosis, unlike TNF-α following infliximab treatment. At 1 year, TNF-α concentration exhibited a negative correlation with infliximab trough levels (Pearson coefficient = -0.500, p = 0.009), and a positive correlation with anti-infliximab antibody titre (Pearson coefficient = 0.510, p = 0.018). The diagnostic capability of 1-year TNF-α concentration to predict achievement of deep remission had an area under the ROC of 0.802 (p = 0.008), with a TNF-α cut-off concentration set at 9.40 pg/mL. Decreased cytokine concentrations following Crohn's disease treatment reflected reduced inflammatory burden. Targeted medical intervention (infliximab) aimed at specific cytokines, such as TNF-α, led to the reduction of the corresponding cytokines. High TNF-α level post-treatment, combined with suboptimal infliximab trough levels and increased antibody formation, may contribute to deep remission failure in patients.

摘要

一项初步研究调查了克罗恩病(CD)儿科患者诊断时的细胞因子谱(白细胞介素-6、肿瘤坏死因子-α、白细胞介素-17A和白细胞介素-10),这些细胞因子对英夫利昔单抗(IFX)谷浓度(TLs)的影响。在这项随访研究中,我们评估了克罗恩病治疗后细胞因子水平的变化。治疗1年后重新测量细胞因子。还对开始英夫利昔单抗治疗的患者测量了英夫利昔单抗谷浓度和总抗英夫利昔单抗抗体。总共纳入了29例在2020年6月至2021年6月被诊断为中度至重度克罗恩病后随访1年的患者。所有细胞因子在1年时的平均浓度显著低于诊断时的浓度。与英夫利昔单抗治疗后的肿瘤坏死因子-α不同,白细胞介素-6、白细胞介素-17A和白细胞介素-10在1年时的浓度仍保持诊断时观察到的相互间的相关性。在1年时,肿瘤坏死因子-α浓度与英夫利昔单抗谷浓度呈负相关(皮尔逊系数=-0.500,p=0.009),与抗英夫利昔单抗抗体滴度呈正相关(皮尔逊系数=0.510,p=0.018)。1年时肿瘤坏死因子-α浓度预测深度缓解达成情况的诊断能力,其ROC曲线下面积为0.802(p=0.008),肿瘤坏死因子-α截断浓度设定为9.40 pg/mL。克罗恩病治疗后细胞因子浓度降低反映了炎症负担减轻。针对特定细胞因子(如肿瘤坏死因子-α)的靶向药物干预(英夫利昔单抗)导致相应细胞因子减少。治疗后肿瘤坏死因子-α水平高,再加上英夫利昔单抗谷浓度不理想和抗体形成增加,可能导致患者深度缓解失败。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89fd/11961661/b9cc3aac13e1/41598_2025_89578_Fig1_HTML.jpg

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