专刊：潜伏性弓形虫感染是否模拟精神分裂症的免疫特征？性别特异性的细胞因子和脑标志物改变提示部分重叠

摘要(中文译文)

精神分裂症常伴有低度神经炎症。由于潜伏性弓形虫病（LT）在精神分裂症个体中更为普遍，我们检验了LT是否会产生一种与精神分裂症中所报道的生物标志物模式相似的标志物模式。我们使用多重免疫分析方法，对65名LT阳性个体和103名匹配的LT阴性对照者定量了15种细胞因子和15种脑损伤血液标志物。通过MANCOVA和PERMANOVA评估感染、年龄、性别及其交互作用的多变量效应。通过偏Kendall相关（控制年龄和性别）检验对单个生物标志物的效应。通过对由偏相关得出的相异性矩阵进行Mantel检验，评估内部相关结构的差异。LT与较高的KLK6、S100B和TDP-43以及较低的MIF相关；其他若干标志物显示出非显著但幅度可观的趋势。感染组的细胞因子显示IFN-γ、IL-1β和MCP-1降低，IL-13和IL-17升高。性别分层分析提示，对脑损伤标志物的效应在女性中更强，而对细胞因子的效应在男性中更强。相关结构也出现分化：感染者脑损伤标志物与细胞因子之间表现出更多负相关，而对照组主要呈正相关（Mantel r = 0.461，p = 0.043）。LT特征与精神分裂症在KLK6和S100B升高方面重叠，在男性中还表现为GDNF降低，但在MIF以及总体细胞因子模式方面形成对比（无一致的IL-6/TNF-α升高）。LT引起神经炎症和神经免疫改变，这些改变仅部分重现精神分裂症；其生物标志物模式及相互关系不同，这反对将LT视为精神分裂症相关神经炎症的主要驱动因素。

Abstract

Schizophrenia often features low-grade neuroinflammation. Because latent toxoplasmosis (LT) is more prevalent among individuals with schizophrenia, we tested whether LT yields a biomarker pattern resembling that reported in schizophrenia. We quantified 15 cytokines and 15 blood markers of brain injury in 65 LT-positive individuals and 103 matched LT-negative controls using multiplex immunoassays. Multivariate effects of infection, age, sex, and their interaction were assessed by MANCOVA and PERMANOVA. Effects on individual biomarkers were tested by partial Kendall correlation (controlling for age and sex). Differences in the internal correlation structure were evaluated with Mantel tests on dissimilarity matrices derived from partial correlations. LT was associated with higher KLK6, S100B, and TDP-43, and lower MIF; several other markers showed nonsignificant but sizable trends. Cytokines showed reduced IFN-γ, IL-1β, and MCP-1, and elevated IL-13 and IL-17 in the infected group. Sex-stratified analyses suggested stronger effects on brain-injury markers in women and on cytokines in men. Correlation structure also diverged: infected individuals exhibited more negative links between brain-injury markers and cytokines, whereas controls showed predominantly positive associations (Mantel r = 0.461, p = 0.043). The LT profile overlapped with schizophrenia in elevated KLK6 and S100B and, in men, reduced GDNF, but contrasted for MIF and for the overall cytokine pattern (no consistent IL-6/TNF-α elevation). LT entails neuroinflammatory and neuroimmune alterations that only partly recapitulate schizophrenia; the biomarker pattern and interrelationships differ, arguing against LT as the main driver of schizophrenia-related neuroinflammation.

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