Miltenberger Emily, Guzmán Janitzio, Rahim Rodaba, Yu Miranda, Makiya Michelle, Adames Castillo Perla, Lee Soo Ching, Nash Theodore E, Klion Amy D, Nutman Thomas B, O'Connell Elise M
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Division of Intramural Research, 10 Center Dr. Bldg 10 Rm 11N206, Bethesda, MD, 20892, USA.
J Neuroinflammation. 2025 Sep 26;22(1):215. doi: 10.1186/s12974-025-03540-1.
Subarachnoid neurocysticercosis (SANCC) is the most severe manifestation of neurocysticercosis. Most complications (communicating hydrocephalus, ischemic stroke, aneurysm, and subarachnoid hemorrhage) are due to inflammation localized to the central nervous system (CNS). The role of eosinophils in the inflammation associated with SANCC has not been previously studied.
Cryopreserved CSF collected as part of a clinical trial for neurocysticercosis (NCC) were assessed for analytes associated with eosinophil activation and recruitment using multiplex bead assays in both subjects with SANCC (n = 28) and in NCC-negative controls (n = 26). The SANCC patients underwent chart review for extraction of clinical variables as well as grouping by disease severity to identify analytes that may be associated with the development of more severe symptoms of SANCC.
Eosinophil granule proteins (EGPs - ECP, EDN, and EPO), markers of eosinophil activation, were elevated in the CSF of SANCC patients compared to controls. Moreover, the eosinophil-associated cytokines/chemokines IL-5, IL-13, IL-18, CCL24/eotaxin-2, and CCL26/eotaxin-3 were also significantly elevated in the CSF of SANCC patients compared to controls. In those for whom there were paired specimens (n = 13) from baseline and following cure, there was a significant reduction in these cytokines/chemokines (except CCL26/eotaxin-3). The percentage of CSF white blood cells that were eosinophils was positively correlated with EDN, EPO, IL-5, IL-13, CCL24, CCL26, CCL8, CCL13, and CCL5/RANTES, as well as the time it took to achieve biomarker cure. When SANCC patients were subdivided between those with severe disease and those with non-severe disease, the levels of eosinophil cationic protein (ECP), the CCR3 ligands (CCL7 and CCL5), CCL4, IL-18, and IL-1RA discriminated clearly between these 2 groups. DISCUSSION: These data provide evidence for eosinophil recruitment and activation in the subarachnoid space in patients with SANCC, as well as for a potential role of eosinophils in driving inflammation-associated complications.
蛛网膜下腔神经囊尾蚴病（SANCC）是神经囊尾蚴病最严重的表现形式。大多数并发症（交通性脑积水、缺血性中风、动脉瘤和蛛网膜下腔出血）是由于局限于中枢神经系统（CNS）的炎症所致。嗜酸性粒细胞在与SANCC相关的炎症中的作用此前尚未得到研究。
作为神经囊尾蚴病（NCC）临床试验一部分收集的冷冻脑脊液，使用多重微珠分析评估与嗜酸性粒细胞激活和募集相关的分析物，样本来自SANCC患者（n = 28）和NCC阴性对照（n = 26）。对SANCC患者的病历进行回顾，以提取临床变量，并按疾病严重程度分组，以确定可能与SANCC更严重症状发展相关的分析物。
与对照组相比，SANCC患者脑脊液中嗜酸性粒细胞颗粒蛋白（EGPs - ECP、EDN和EPO），即嗜酸性粒细胞激活的标志物升高。此外，与对照组相比，SANCC患者脑脊液中与嗜酸性粒细胞相关的细胞因子/趋化因子IL-5、IL-13、IL-18、CCL24/嗜酸性粒细胞趋化因子-2和CCL26/嗜酸性粒细胞趋化因子-3也显著升高。在有基线和治愈后配对标本的患者中（n = 13），这些细胞因子/趋化因子（CCL26/嗜酸性粒细胞趋化因子-3除外）有显著降低。脑脊液中嗜酸性粒细胞占白细胞的百分比与EDN、EPO、IL-5、IL-13、CCL24、CCL26、CCL8、CCL13和CCL5/调节激活正常T细胞表达和分泌因子呈正相关，也与实现生物标志物治愈所需的时间呈正相关。当将SANCC患者分为重症患者和非重症患者时，嗜酸性粒细胞阳离子蛋白（ECP）、CCR3配体（CCL7和CCL5）、CCL4、IL-18和IL-1RA的水平在这两组之间有明显区分。
这些数据为SANCC患者蛛网膜下腔中嗜酸性粒细胞的募集和激活提供了证据，并证明嗜酸性粒细胞在引发炎症相关并发症中可能发挥作用。
