中枢神经系统结节病中的脑脊液细胞因子和趋化因子谱：诊断和免疫病理见解。
Cerebrospinal Fluid Cytokine and Chemokine Profiles in Central Nervous System Sarcoidosis: Diagnostic and Immunopathologic Insights.
机构信息
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Department of Neurology, Mayo Clinic, Rochester, MN, USA.
出版信息
Ann Neurol. 2024 Oct;96(4):704-714. doi: 10.1002/ana.27024. Epub 2024 Jul 19.
OBJECTIVE
To evaluate the cerebrospinal fluid (CSF) cytokine/chemokine profile of central nervous system (CNS) neurosarcoidosis (NS), and its utility in differential diagnosis, treatment, and prognostication.
METHODS
In this case-control study, we validated 17 cytokines/chemokines (interleukin [IL]-1-beta, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, IL-17A, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and tumor necrosis factor [TNF]-alpha) in a multiplexed automated immunoassay system (ELLA; Bio-Techne, Minneapolis, MN, USA), and assessed them in CSF and serum of symptomatic patients with probable or definite CNS NS (01/2011-02/2023) with gadolinium enhancement and/or CSF pleocytosis. Patients with multiple sclerosis, primary CNS lymphoma, aquaporin-4 immunoglobulin G positivity, non-inflammatory disorders, and healthy individuals were used as controls.
RESULTS
A total of 32 NS patients (59% women; median age, 59 years [19-81]) were included; concurrent sera were available in 12. CSF controls consisted of 26 multiple sclerosis, 8 primary CNS lymphoma, 84 aquaporin-4 immunoglobulin G positive, and 34 patients with non-inflammatory disorders. Gadolinium enhancement was present in 31 of 32 NS patients, and CSF pleocytosis in 27 of 32 (84%). CSF IL-2, IL-6, IL-10, IL-13, BAFF, IL-8/CXCL8, CXCL9, CXCL10, CXCL13, GM-CSF, interferon-gamma, and TNF-alpha levels were significantly higher in NS patients compared with non-inflammatory controls (p ≤ 0.02); elevations were more common in CSF than serum. Concurrent elevation of IL-6, CXCL9, CXCL10, GM-CSF, interferon-gamma, and TNF-alpha was present in 18 of 32 NS patients, but only in 1 control. Elevated IL-6, IL-10, IL-13, CXCL9, CXL10, GM-CSF, and TNF-alpha associated with measures of disease activity.
INTERPRETATION
NS CSF cytokine/chemokine profiles suggest T cell (mainly T helper cell type 1), macrophage, and B-cell involvement. These signatures aid in NS diagnosis, indicate disease activity, and suggest therapeutic avenues. ANN NEUROL 2024;96:704-714.
目的
评估中枢神经系统（CNS）神经结节病（NS）的脑脊液（CSF）细胞因子/趋化因子谱，并评估其在鉴别诊断、治疗和预后方面的应用。
方法
在这项病例对照研究中，我们使用多重自动化免疫分析系统（ELLA；美国明尼苏达州明尼阿波利斯市的 Bio-Techne）验证了 17 种细胞因子/趋化因子（白细胞介素[IL]-1β、IL-2、IL-4、IL-5、IL-6、IL-10、IL-12p70、IL-13、IL-17A、BAFF、IL-8/CXCL8、CXCL9、CXCL10、CXCL13、GM-CSF、干扰素-γ和肿瘤坏死因子-α），并评估了它们在有症状的疑似或明确的 CNS NS（2011 年 1 月至 2023 年 2 月）患者的 CSF 和血清中的水平，这些患者存在钆增强和/或 CSF 白细胞增多。多发性硬化症、原发性中枢神经系统淋巴瘤、水通道蛋白 4 免疫球蛋白 G 阳性、非炎症性疾病和健康个体被用作对照。
结果
共纳入 32 名 NS 患者（59%为女性；中位年龄 59 岁[19-81]）；12 名患者同时提供了血清。CSF 对照组包括 26 名多发性硬化症患者、8 名原发性中枢神经系统淋巴瘤患者、84 名水通道蛋白 4 免疫球蛋白 G 阳性患者和 34 名非炎症性疾病患者。31 名 NS 患者存在钆增强，27 名患者存在 CSF 白细胞增多（84%）。与非炎症性对照组相比，NS 患者的 CSF IL-2、IL-6、IL-10、IL-13、BAFF、IL-8/CXCL8、CXCL9、CXCL10、CXCL13、GM-CSF、干扰素-γ和 TNF-α水平明显升高（p≤0.02）；CSF 中的升高比血清中更常见。18 名 NS 患者中有 18 名同时存在升高的 IL-6、CXCL9、CXCL10、GM-CSF、干扰素-γ和 TNF-α，但只有 1 名对照存在。升高的 IL-6、IL-10、IL-13、CXCL9、CXCL10、GM-CSF 和 TNF-α与疾病活动度的指标相关。
结论
NS 的 CSF 细胞因子/趋化因子谱提示存在 T 细胞（主要是辅助性 T 细胞 1 型）、巨噬细胞和 B 细胞的参与。这些特征有助于 NS 的诊断、提示疾病活动度，并提示治疗途径。
Zotero 插件