TNFAIP3在儿童社区获得性肺炎血浆中的表达及临床意义
The Expression and Clinical Significance of TNFAIP3 in the Plasma of Children with Community-Acquired Pneumonia
DOI: 10.12677/acm.2026.1652154, PDF,   
作者: 刘昭宏:内蒙古科技大学包头医学院研究生院,内蒙古 包头;内蒙古自治区人民医院儿科,内蒙古 呼和浩特;于少飞*:内蒙古自治区人民医院儿科,内蒙古 呼和浩特
关键词: TNFAIP3儿童社区获得性肺炎血浆炎症反应临床意义TNFAIP3 Children with Community-Acquired Pneumonian Plasma Inflammatory Response Clinical Significance
摘要: 目的:分析社区获得性肺炎(CAP)患儿血浆中肿瘤坏死因子α诱导蛋白3 (TNFAIP3)、肿瘤坏死因子α (TNF-α)、白细胞介素-6 (IL-6)的表达水平,探究其与病情严重程度及预后的关系,为CAP患儿早期识别、病情评估及治疗提供依据。方法:选取2024年6月至2025年10月内蒙古自治区人民医院儿科90例CAP患儿,分为轻症组(50例)和重症组(40例),另选25例健康儿童为对照组。采集各组静脉血,采用ELISA法测定血浆TNFAIP3、TNF-α、IL-6水平,结合ROC曲线分析其对CAP严重程度及预后的预测价值,对数据进行统计分析。结果:1) 重症CAP患儿发热、住院时间显著延长,喘息、肺实变、肺不张发生率及白细胞、中性粒细胞绝对值、CRP、LDH水平均高于轻症组(均P < 0.05);2) 重症组急性期血浆TNFAIP3、TNF-α、IL-6水平高于轻症组及对照组,轻症组高于对照组,且两组急性期上述指标均高于恢复期(均P < 0.05);3) 急性期TNF-α与IL-6呈正相关,TNFAIP3与TNF-α和IL-6呈负相关(均P < 0.05);4) ROC曲线显示,TNFAIP3、TNF-α、IL-6的AUC均 > 0.7,联合诊断AUC达0.93,优于单个指标。结论:TNFAIP3、TNF-α、IL-6参与儿童CAP急性炎症反应,其水平可反映病情严重程度;重症CAP患儿可能存在促炎因子过度表达,而抑炎因子代偿性升高但不足以完全抑制炎症风暴;三者联合检测对早期识别重症CAP、评估病情具有重要潜在价值。
Abstract: Objective: This paper aims to analyze the expression levels of plasma tumor necrosis factor-α-induced protein 3 (TNFAIP3), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in children with community-acquired pneumonia (CAP), explore their relationships with disease severity and prognosis, and provide evidence for early identification, severity assessment, and treatment in children with CAP. Methods: Ninety children with CAP admitted to the Department of Pediatrics, Inner Mongolia People’s Hospital from June 2024 to October 2025 were enrolled and divided into a mild group (n = 50) and a severe group (n = 40). Another 25 healthy children were selected as the control group. Venous blood samples were collected from all groups. Plasma levels of TNFAIP3, TNF-α, and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA). The predictive value of these indicators for CAP severity and prognosis was analyzed using receiver operating characteristic (ROC) curves, and statistical analysis was performed. Results: 1) In children with severe CAP, fever duration and length of hospital stay were significantly prolonged; the incidence rates of wheezing, lung consolidation, and atelectasis, as well as levels of white blood cells, absolute neutrophil count, CRP, and LDH, were all higher than those in the mild group (all P < 0.05). 2) Plasma levels of TNFAIP3, TNF-α, and IL-6 in the acute phase were higher in the severe group than in the mild and control groups, and higher in the mild group than in the control group. Levels of these indicators in the acute phase were higher than those in the recovery phase in both groups (all P < 0.05). 3) In the acute phase, TNF-α was positively correlated with IL-6, while TNFAIP3 was negatively correlated with TNF-α and IL-6 (all P < 0.05). 4) ROC curves showed that the AUC values of TNFAIP3, TNF-α, and IL-6 were all > 0.7, and the AUC of combined diagnosis reached 0.93, which was superior to any single indicator. Conclusion: TNFAIP3, TNF-α, and IL-6 are involved in the acute inflammatory response in pediatric CAP, and their levels can reflect disease severity. Children with severe CAP may have overexpression of pro-inflammatory cytokines, while anti-inflammatory cytokines rise compensatorily yet are insufficient to completely inhibit the inflammatory storm. Combined detection of the three indicators has important potential value for early identification of severe CAP and disease assessment.
文章引用:刘昭宏, 于少飞. TNFAIP3在儿童社区获得性肺炎血浆中的表达及临床意义[J]. 临床医学进展, 2026, 16(5): 3321-3332. https://doi.org/10.12677/acm.2026.1652154

参考文献

[1] Perin, J., Mulick, A., Yeung, D., Villavicencio, F., Lopez, G., Strong, K.L., et al. (2022) Global, Regional, and National Causes of Under-5 Mortality in 2000-19: An Updated Systematic Analysis with Implications for the Sustainable Development Goals. The Lancet Child & Adolescent Health, 6, 106-115. [Google Scholar] [CrossRef] [PubMed]
[2] Paulson, K.R., Kamath, A.M., Alam, T., Bienhoff, K., Abady, G.G., Abbas, J., et al. (2021) Global, Regional, and National Progress towards Sustainable Development Goal 3.2 for Neonatal and Child Health: All-Cause and Cause-Specific Mortality Findings from the Global Burden of Disease Study 2019. The Lancet, 398, 870-905. [Google Scholar] [CrossRef] [PubMed]
[3] Yamamoto, S., Hagihara, T., Horiuchi, Y., Okui, A., Wani, S., Yoshida, T., et al. (2017) Mediator Cyclin-Dependent Kinases Upregulate Transcription of Inflammatory Genes in Cooperation with NF-κB and C/EBPβ on Stimulation of Toll-Like Receptor 9. Genes to Cells, 22, 265-276. [Google Scholar] [CrossRef] [PubMed]
[4] Ma, L., Ge, S. and Song, D. (2025) Predictive Value of CCL26 and CCR3 Levels for Prognosis Assessment in Children with Mycoplasma Pneumoniae Pneumonia Treated with Azithromycin. Translational Pediatrics, 14, 1806-1815. [Google Scholar] [CrossRef
[5] Wang, G., Liu, J., Yu, X. and Cao, S. (2025) The Value of Combined Examination of Serum Serum Heparin Binding Protein, Tumor Necrosis Factor Alpha, Interleukin-6, Platelet Count, and C-Reactive Protein in Evaluating the Condition and Prognosis of Children with Adenovirus Pneumonia. Frontiers in Pediatrics, 13, Article 1620206. [Google Scholar] [CrossRef
[6] Mooney, E.C. and Sahingur, S.E. (2020) The Ubiquitin System and A20: Implications in Health and Disease. Journal of Dental Research, 100, 10-20. [Google Scholar] [CrossRef] [PubMed]
[7] Priem, D., van Loo, G. and Bertrand, M.J.M. (2020) A20 and Cell Death-Driven Inflammation. Trends in Immunology, 41, 421-435. [Google Scholar] [CrossRef] [PubMed]
[8] Wang, Y., Song, Z., Bi, J., Liu, J., Tong, L., Song, Y., et al. (2017) A20 Protein Regulates Lipopolysaccharide-Induced Acute Lung Injury by Downregulation of NF-κB and Macrophage Polarization in Rats. Molecular Medicine Reports, 16, 4964-4972. [Google Scholar] [CrossRef] [PubMed]
[9] 诸福棠实用儿科学(第9版) [M]. 北京: 人民卫生出版社, 2022: 1364.
[10] 中华医学会儿科学分会呼吸学组, 中华儿科杂志编辑委员会, 中国医药教育协会儿科专业委员会. 儿童社区获得性肺炎管理指南(2024修订) [J]. 中华儿科杂志, 2024, 62(10): 920-930.
[11] Zhao, M., Wang, B., Zhou, F., Fang, C., Zhu, B., Zhou, M., et al. (2025) Modeling “Two-Hit” Severe Pneumonia in Mice: Pathological Characteristics and Mechanistic Studies. Inflammation, 48, 1460-1483. [Google Scholar] [CrossRef] [PubMed]
[12] Alharbi, K.S., Fuloria, N.K., Fuloria, S., Rahman, S.B., Al-Malki, W.H., Javed Shaikh, M.A., et al. (2021) Nuclear Factor-Kappa B and Its Role in Inflammatory Lung Disease. Chemico-Biological Interactions, 345, Article 109568. [Google Scholar] [CrossRef] [PubMed]
[13] Fernandez-Botran, R., Uriarte, S.M., Arnold, F.W., Rodriguez-Hernandez, L., Rane, M.J., Peyrani, P., et al. (2014) Contrasting Inflammatory Responses in Severe and Non-Severe Community-Acquired Pneumonia. Inflammation, 37, 1158-1166. [Google Scholar] [CrossRef] [PubMed]
[14] Haugen, J., Chandyo, R.K., Brokstad, K.A., Mathisen, M., Ulak, M., Basnet, S., et al. (2015) Cytokine Concentrations in Plasma from Children with Severe and Non-Severe Community Acquired Pneumonia. PLOS ONE, 10, e0138978. [Google Scholar] [CrossRef] [PubMed]
[15] Chen, Y., Luo, G., Yuan, J., Wang, Y., Yang, X., Wang, X., et al. (2014) Vitamin C Mitigates Oxidative Stress and Tumor Necrosis Factor-Alpha in Severe Community-Acquired Pneumonia and LPS-Induced Macrophages. Mediators of Inflammation, 2014, 1-11. [Google Scholar] [CrossRef] [PubMed]
[16] Pinna, F., Bissinger, M., Beuke, K., Huber, N., Longerich, T., Kummer, U., et al. (2017) A20/TNFAIP3 Discriminates Tumor Necrosis Factor (TNF)-Induced NF-κB from JNK Pathway Activation in Hepatocytes. Frontiers in Physiology, 8, Article 610. [Google Scholar] [CrossRef] [PubMed]
[17] Buys, W., Bick, A., Madel, R.J., Westendorf, A.M., Buer, J., Herbstreit, F., et al. (2023) Substantial Heterogeneity of Inflammatory Cytokine Production and Its Inhibition by a Triple Cocktail of Toll-Like Receptor Blockers in Early Sepsis. Frontiers in Immunology, 14, Article 1277033. [Google Scholar] [CrossRef] [PubMed]
[18] Shigemura, T., Kaneko, N., Kobayashi, N., Kobayashi, K., Takeuchi, Y., Nakano, N., et al. (2016) Novel Heterozygous C243Y A20/TNFAIP3 Gene Mutation Is Responsible for Chronic Inflammation in Autosomal-Dominant Behçet’s Disease. RMD Open, 2, e000223. [Google Scholar] [CrossRef] [PubMed]
[19] Li, J., Zhu, C., Meng, Y., Zhang, L., Liu, C., Qin, Y., et al. (2025) Zika Virus Inhibits Cell Death by Inhibiting the Expression of NLRP3 and A20. Journal of Virology, 99, e0198024. [Google Scholar] [CrossRef] [PubMed]
[20] Gao, L., Coope, H., Grant, S., Ma, A., Ley, S.C. and Harhaj, E.W. (2011) ABIN1 Protein Cooperates with TAX1BP1 and A20 Proteins to Inhibit Antiviral Signaling. Journal of Biological Chemistry, 286, 36592-36602. [Google Scholar] [CrossRef] [PubMed]
[21] Kelly, C., Shields, M.D., Elborn, J.S., et al. (2011) A20 Regulation of Nuclear Factor-κB: Perspectives for Inflammatory Lung Disease. American Journal of Respiratory Cell and Molecular Biology, 44, 743-748.
[22] Momtazi, G., Lambrecht, B.N., Naranjo, J.R. and Schock, B.C. (2019) Regulators of A20 (TNFAIP3): New Drug-Able Targets in Inflammation. American Journal of Physiology-Lung Cellular and Molecular Physiology, 316, L456-L469. [Google Scholar] [CrossRef] [PubMed]
[23] Momtazi, G., Elbanna, A., Finnegan, S., et al. (2019) NF-κB Activation in Cystic Fibrosis: The Dream of A20. European Respiratory Journal, 54, PA2371. [Google Scholar] [CrossRef