Neurocysticercosis: the effectiveness of the cysticidal treatment could be influenced by the host immunity
Neurocysticercosis: the effectiveness of the cysticidal treatment could be influenced by the host immunity
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DOI：
10.1007/s00430-014-0345-2
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发表时间：
2014-12-01
影响因子：
5.4
通讯作者：
Fleury, Agnes
中科院分区：
文献类型：
--
作者：
Cardenas, Graciela;Fragoso, Gladis;Fleury, Agnes
脑囊虫病是一种临床和放射学上的多形性寄生虫病，目前仍流行于拉丁美洲、非洲和亚洲的大多数不发达国家。抗寄生虫药物(AHD)通常是有效的，并能迅速摧毁囊虫病。相反，几个周期的AHD往往是必要的，以损害位于实质外的寄生虫。本研究旨在评估患者免疫学特征的差异是否涉及对AHD反应的多样性。为此，进行了全球基因表达微阵列和细胞因子分析。有反应的患者是那些在AHD治疗后显示寄生虫负担减少超过50%的放射学患者。微阵列治疗前后的比较显示，在5名有应答的患者中，共有18个免疫相关基因上调，这与4名无应答的受试者的表达谱有关。上调基因的功能包括促炎(ROR Gamma C、Sema4a、SLAMF3、SLAMF6)、抗炎(TGFβ、TNFRSF25、TNFRS18、SLAMF1、ILF2)或免疫调节(CXCL2、RUNX3、SLAMF9、TGFBR3)。为了进一步探讨治疗反应异质性的原因，对39名有效和26名无应答患者的血清、PBMC上清液和脑脊液进行了广泛的ELISA细胞因子分析。有效组治疗后60d脑脊液IL-17A水平升高(P=0.04)，培养上清液IL-6水平升高(P=0.03)。这些结果提示，放射学方法观察到的促炎细胞因子对AHD的反应可能有影响，因此宿主免疫可能参与了AHD治疗的有效性。
Neurocysticercosis, a clinically and radiologically pleomorphic parasitic disease, is still endemic to most non-developed countries of Latin America, Africa, and Asia. Anti-helminthic drugs (AHD) are generally effective and rapidly destroy parenchymal cysticerci. In contrast, several cycles of AHD are frequently necessary to damage extraparenchymally located parasites. The present study was designed to evaluate whether differences in the immunological profile of the patients is involved in the diversity of the response to AHD. To this end, a global gene expression microarray and a cytokine analysis were made. Responder patients were those showing a radiological reduction greater than 50 % in the parasite burden following AHD treatment. Microarray pre- and post-treatment comparisons showed that a total of eighteen immune-related genes were up-regulated in the five responder patients with respect the expression profile seen in the four non-responder subjects. The function of up-regulated genes exerted pro-inflammatory (ROR gamma C, Sema4A, SLAMF3, SLAMF6), anti-inflammatory (TGF beta, TNFRSF25, TNFRS18, SLAMF1, ILF2), or immunomodulatory effects (CXCL2, RUNX3, SLAMF9, TGFBR3). To further explore the causes of the heterogeneity in the response to treatment, a wide ELISA cytokine analysis was performed in serum, PBMC supernatants, and CSF samples from 39 responder and 26 non-responder patients. Responder patients showed higher CSF IL-17A levels (P = 0.04) and higher supernatant IL-6 levels (P = 0.03) 60 days after treatment. These results suggest a possible influence of pro-inflammatory cytokines on the response to AHD as observed by radiological methods, and thus the possible participation of the host immunity in the effectiveness of AHD treatment.