Bojkiewicz Ewa, Toczylowski Kacper, Lewandowski Dawid, Martonik Diana, Flisiak Robert, Sulik Artur
Department of Pediatric Infectious Diseases, Medical University of Bialystok, Bialystok, Poland.
Department of Infectious Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland.
J Inflamm Res. 2024 Dec 5;17:10239-10254. doi: 10.2147/JIR.S480556. eCollection 2024.
Chitinase 3-like-1 (CHI3L1), also known as YKL-40, is a potential biomarker for neuroinflammatory conditions. It is upregulated in Alzheimer's disease, multiple sclerosis, and traumatic brain injury. However, its involvement in pediatric tick-borne encephalitis (TBE) has not been addressed yet. This study aimed to evaluate CHI3L1 and its relationship with other inflammatory cytokines, blood-brain barrier (BBB) integrity, immune response, and disease severity in pediatric patients with TBE.
A total of 22 pediatric TBE patients hospitalized in Bialystok, Poland were included in this study. Participants were categorized as having meningoencephalitis (n=6) or meningitis (n=16). The integrity of the brain-blood barrier (BBB) was assessed using the albumin quotient (albQ). Biomarker indices were calculated to account for variations in BBB permeability. The concentrations of CHI3L1, CCL2, chemerin, CXCL2, IFN-γ, IL-1-β, IL-4, IL-6, IL-13, and TNF-α in both serum and CSF, were measured using the Luminex Multiplex Assay od admission and two weeks later when symptoms resolved.
CSF and serum concentrations of CHI3L1 did not differ between the encephalitis and meningitis cases. After adjusting for BBB permeability, the CHI3L1 index was 2.4-fold lower in patients with encephalitis than in those with meningitis (P=0.008). There was a post-treatment reduction of CHI3L1, IL-6, and TNF-α CSF concentrations. We also found and improvement in BBB permeability in younger children but in older albQ remained abnormal. Correlation analysis revealed associations between CHI3L1 levels and pro-inflammatory markers, notably chemerin, IL-6, and TNF-α, across both clinical groups.
Our findings suggest that CHI3L1 CSF levels reflect the inflammatory activity in pediatric TBE and may help to differentiate between meningoencephalitis and meningitis. The observed interactions between CHI3L1 and other cytokines underscore its potential involvement in inflammatory response to the virus. The prolonged disruption in BBB integrity in older children might reflect age-dependent differences in the severity of TBE. These insights advance our understanding of TBE pathogenesis in children and support further investigation of CHI3L1 as a biomarker for TBE diagnosis and management.
几丁质酶3样蛋白1（CHI3L1），也称为YKL - 40，是神经炎症性疾病的潜在生物标志物。它在阿尔茨海默病、多发性硬化症和创伤性脑损伤中上调。然而，其在儿童蜱传脑炎（TBE）中的作用尚未得到研究。本研究旨在评估儿童TBE患者中CHI3L1及其与其他炎性细胞因子、血脑屏障（BBB）完整性、免疫反应和疾病严重程度的关系。
本研究纳入了波兰比亚韦斯托克住院的22例儿童TBE患者。参与者被分为脑膜脑炎组（n = 6）或脑膜炎组（n = 16）。使用白蛋白商数（albQ）评估脑血屏障（BBB）的完整性。计算生物标志物指数以考虑BBB通透性的变化。使用Luminex多重检测法在入院时和症状缓解两周后测量血清和脑脊液中CHI3L1、CCL2、chemerin、CXCL2、IFN - γ、IL - 1 - β、IL - 4、IL - 6、IL - 13和TNF - α的浓度。
脑炎和脑膜炎病例的脑脊液和血清CHI3L1浓度无差异。在调整BBB通透性后，脑炎患者的CHI3L1指数比脑膜炎患者低2.4倍（P = 0.008）。治疗后脑脊液中CHI3L1、IL - 6和TNF - α浓度降低。我们还发现年幼儿童的BBB通透性有所改善，但年长儿童的albQ仍异常。相关性分析显示，在两个临床组中，CHI3L1水平与促炎标志物之间存在关联，尤其是chemerin、IL - 6和TNF - α。
我们的研究结果表明，脑脊液中CHI3L1水平反映了儿童TBE中的炎症活动，可能有助于区分脑膜脑炎和脑膜炎。观察到的CHI3L1与其他细胞因子之间的相互作用强调了其在对病毒炎症反应中的潜在作用。年长儿童BBB完整性的长期破坏可能反映了TBE严重程度的年龄依赖性差异。这些见解增进了我们对儿童TBE发病机制的理解，并支持进一步研究CHI3L1作为TBE诊断和管理的生物标志物。
