Dengue is a rapidly emerging pandemic-prone disease, whose manifestations range from asymptomatic infection to life-threatening complications like Dengue Hemorrhagic Fever and Dengue Shock Syndrome. This study investigates and compares the immune response in clinically defined cohorts of Dengue with and without warning signs, with the aim of identifying immunological correlates of clinical disease and potential markers of disease severity. Blood samples, collected from study participants fulfilling the WHO definition of Dengue with and without warning signs and healthy volunteers, were analyzed using flow cell-based fluorometric methods for cytokines and chemokines. Gene expression analysis, using RT-PCR, was conducted on T helper cell subset-specific transcription factors and cytokines. Demographic details, virological markers, serotype distribution, and hematological parameters were also investigated in all the subjects. The 35 participants recruited in the study, included 11 healthy volunteers and 12 patients each fulfilling the WHO criteria of Dengue with and without warning signs. While the demographic characteristics and serotype distribution was similar in Dengue with and without warning signs cohorts of the disease, platelet counts and Aspartate Aminotransferase (AST) levels changed significantly between Dengue with and without warning signs patients. Plasma cytokine analysis showed up-regulation of IL-4, IL-10, IP-10, and MCP-1 in Dengue patients compared to healthy volunteers. Disease severity was associated with elevated levels of IL-10, IP-10, IL-4, MCP-1, and MIP-1α. IL-8 and MIP-1α were significantly up-regulated in Dengue with warning sign compared to Dengue without warning signs cases. Transcription factor analysis indicated increased expression of RORα, FoxP3, and GATA3 in Dengue patients. mRNA expression of TGFβ and IL-4 was also elevated in Dengue patients. A positive correlation between mRNA expression of IL-4 and plasma IL-4 was observed. The study reveals a Th2-predominant immune response in all Dengue patients, regardless of disease severity, with overexpression of IL-8 and MIP-1α being observed in patients with warning signs.

中文翻译：

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Th2为主的免疫反应是登革热发病机制的基础

登革热是一种迅速出现的大流行性疾病，其表现范围从无症状感染到危及生命的并发症，如登革出血热和登革休克综合症。本研究调查并比较了临床定义的有或没有警告信号的登革热群体的免疫反应，目的是确定临床疾病的免疫相关性和疾病严重程度的潜在标志物。使用基于流式细胞的荧光方法对细胞因子和趋化因子进行分析，从符合世界卫生组织对有或没有警告信号的登革热定义的研究参与者和健康志愿者收集血液样本。使用 RT-PCR 对 T 辅助细胞亚群特异性转录因子和细胞因子进行基因表达分析。还对所有受试者进行了人口统计详细信息、病毒学标记、血清型分布和血液学参数的调查。该研究招募了 35 名参与者，其中包括 11 名健康志愿者和 12 名患者，每人均符合世界卫生组织关于有或没有警告症状的登革热标准。虽然有和没有警告标志的登革热疾病组的人口统计学特征和血清型分布相似，但有和没有警告标志的登革热患者之间的血小板计数和天冬氨酸转氨酶（AST）水平存在显着变化。血浆细胞因子分析显示，与健康志愿者相比，登革热患者的 IL-4、IL-10、IP-10 和 MCP-1 表达上调。疾病严重程度与 IL-10、IP-10、IL-4、MCP-1 和 MIP-1α 水平升高相关。与无警告信号的登革热病例相比，有警告信号的登革热病例中 IL-8 和 MIP-1α 的表达显着上调。转录因子分析表明登革热患者中 RORα、FoxP3 和 GATA3 的表达增加。登革热患者中 TGFβ 和 IL-4 的 mRNA 表达也升高。观察到IL-4 mRNA表达与血浆IL-4呈正相关。该研究揭示了所有登革热患者的免疫反应均以 Th2 为主，无论疾病严重程度如何，在有警告信号的患者中观察到 IL-8 和 MIP-1α 的过度表达。