Silva Maria Luiza, Espírito-Santo Luçandra Ramos, Martins Marina Angela, Silveira-Lemos Denise, Peruhype-Magalhães Vanessa, Caminha Ricardo Carvalho, de Andrade Maranhão-Filho Péricles, Auxiliadora-Martins Maria, de Menezes Martins Reinaldo, Galler Ricardo, da Silva Freire Marcos, Marcovistz Rugimar, Homma Akira, Teuwen Dirk E, Elói-Santos Silvana Maria, Andrade Mariléia Chaves, Teixeira-Carvalho Andréa, Martins-Filho Olindo Assis
Laboratório de Biomarcadores de Diagnóstico e Monitoração, Centro de Pesquisas René Rachou, FIOCRUZ/Minas, Avenida Augusto de Lima 1715, Barro Preto, Belo Horizonte, Minas Gerais 30190-002, Brazil.
Clin Vaccine Immunol. 2010 Jan;17(1):118-26. doi: 10.1128/CVI.00369-09. Epub 2009 Nov 11.
Yellow fever (YF) vaccines (17D-204 and 17DD) are well tolerated and cause very low rates of severe adverse events (YEL-SAE), such as serious allergic reactions, neurotropic adverse diseases (YEL-AND), and viscerotropic diseases (YEL-AVD). Viral and host factors have been postulated to explain the basis of YEL-SAE. However, the mechanisms underlying the occurrence of YEL-SAE remain unknown. The present report provides a detailed immunological analysis of a 23-year-old female patient. The patient developed a suspected case of severe YEL-AVD with encephalitis, as well as with pancreatitis and myositis, following receipt of a 17D-204 YF vaccination. The patient exhibited a decreased level of expression of Fc-gammaR in monocytes (CD16, CD32, and CD64), along with increased levels of NK T cells (an increased CD3(+) CD16(+/-) CD56(+/-)/CD3(+) ratio), activated T cells (CD4(+) and CD8(+) cells), and B lymphocytes. Enhanced levels of plasmatic cytokines (interleukin-6 [IL-6], IL-17, IL-4, IL-5, and IL-10) as well as an exacerbated ex vivo intracytoplasmic cytokine pattern, mainly observed within NK cells (gamma interferon positive [IFN-gamma(+)], tumor necrosis factor alpha positive [TNF-alpha(+)], and IL-4 positive [IL-4(+)]), CD8(+) T cells (IL-4(+) and IL-5(+)), and B lymphocytes (TNF-alpha(+), IL-4(+), and IL-10(+)). The analysis of CD4(+) T cells revealed a complex profile that consisted of an increased frequency of IL-12(+) and IFN-gamma(+) cells and a decreased percentage of TNF-alpha(+), IL-4(+), and IL-5(+) cells. Depressed cytokine synthesis was observed in monocytes (TNF-alpha(+)) following the provision of antigenic stimuli in vitro. These results support the hypothesis that a strong adaptive response and abnormalities in the innate immune system may be involved in the establishment of YEL-AND and YEL-AVD.
黄热病（YF）疫苗（17D - 204和17DD）耐受性良好，严重不良事件（YEL - SAE）发生率极低，如严重过敏反应、嗜神经不良疾病（YEL - AND）和嗜内脏疾病（YEL - AVD）。病毒和宿主因素被认为可解释YEL - SAE的发生基础。然而，YEL - SAE发生的潜在机制仍不清楚。本报告对一名23岁女性患者进行了详细的免疫学分析。该患者在接种17D - 204黄热病疫苗后出现疑似严重YEL - AVD病例，伴有脑炎，以及胰腺炎和肌炎。患者单核细胞（CD16、CD32和CD64）中Fc - γR表达水平降低，同时自然杀伤T细胞水平升高（CD3(+) CD16(+/-) CD56(+/-)/CD3(+)比值增加）、活化T细胞（CD4(+)和CD8(+)细胞）以及B淋巴细胞水平升高。血浆细胞因子（白细胞介素 - 6 [IL - 6]、IL - 17、IL - 4、IL - 5和IL - 10）水平升高，以及体外胞浆内细胞因子模式加剧，主要见于自然杀伤细胞（γ干扰素阳性[IFN - γ(+)]、肿瘤坏死因子α阳性[TNF - α(+)]和IL - 4阳性[IL - 4(+)]）、CD8(+) T细胞（IL - 4(+)和IL - 5(+)）以及B淋巴细胞（TNF - α(+)、IL - 4(+)和IL - 10(+)）。对CD4(+) T细胞的分析显示出复杂的特征，包括IL - 12(+)和IFN - γ(+)细胞频率增加，以及TNF - α(+)、IL - 4(+)和IL - 5(+)细胞百分比降低。在体外提供抗原刺激后，单核细胞（TNF - α(+)）中观察到细胞因子合成受抑。这些结果支持以下假设：强烈的适应性反应和先天性免疫系统异常可能与YEL - AND和YEL - AVD的发生有关。
