Paracoccidioides brasiliensis disseminated disease in a patient with inherited deficiency in the β1 subunit of the interleukin (IL)-12/IL-23 receptor
Paracoccidioides brasiliensis disseminated disease in a patient with inherited deficiency in the β1 subunit of the interleukin (IL)-12/IL-23 receptor
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DOI：
10.1086/432119
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发表时间：
2005-08-15
影响因子：
11.8
通讯作者：
Duarte, AJS
中科院分区：
文献类型：
--
作者：
de Moraes-Vasconcelos, D;Grumach, AS;Duarte, AJS
背景。巴西副球孢子菌是一种兼性细胞内二形性真菌，可引起副球孢子菌病 (PCM)，这是拉丁美洲最重要的深部真菌病。只有一小部分被巴西假单胞菌感染的个体会出现临床 PCM，部分原因可能是遗传决定的个体间宿主免疫力的变异性。然而，原发性免疫缺陷尚未与 PCM.Methods 相关。据我们所知，我们描述了第一例患有 PCM 的患者，并且白细胞介素 (IL)-12/IL-23 受体的 β1 亚基存在明确的原发性免疫缺陷，这种疾病以前被证明与干扰素 (IFN)-γ 产生受损、分枝杆菌病和沙门氏菌病特别相关。结果。我们的患者有卡介苗病和非伤寒沙门氏菌病的童年病史，并在 20 岁时以播散性（急性）形式的 PCM 到我们诊所就诊。他对抗真菌治疗反应良好，现在 24 岁，情况良好。结论。这一独特的观察结果支持了先前对 PCM 的研究，表明 IL-12、IL-23 和 IFN-γ 在巴西疟原虫的保护性免疫中发挥着重要作用。因此，结核病和 PCM 不仅在临床和病理学上相关，而且在免疫发病机制上也相关。我们的研究进一步扩大了 IL-12/IL-23-IFN-gamma 轴遗传性缺陷的临床表现范围。患有不明原因深部真菌感染（例如 PCM）的患者应检测 IL-12/IL-23-IFN-gamma 轴缺陷。
Background. Paracoccidioides brasiliensis is a facultative intracellular dimorphic fungus that causes paracoccidioidomycosis (PCM), the most important deep mycosis in Latin America. Only a small percentage of individuals infected by P. brasiliensis develop clinical PCM, possibly in part because of genetically determined interindividual variability of host immunity. However, no primary immunodeficiency has ever been associated with PCM.Methods. We describe the first patient, to our knowledge, with PCM and a well-defined primary immunodeficiency in the beta 1 subunit of the interleukin (IL)-12/IL-23 receptor, a disorder previously shown to be specifically associated with impaired interferon (IFN)-gamma production, mycobacteriosis, and salmonellosis.Results. Our patient had a childhood history of bacille Calmette-Guerin disease and nontyphoid salmonellosis and, at the age of 20 years, presented to our clinic with a disseminated (acute) form of PCM. He responded well to antifungal treatment and is now doing well at 24 years of age.Conclusions. This unique observation supports previous studies of PCM suggesting that IL-12, IL-23, and IFN-gamma play an important role in protective immunity to P. brasiliensis. Tuberculosis and PCM are thus not only related clinically and pathologically, but also by their immunological pathogenesis. Our study further expands the spectrum of clinical manifestations of inherited defects of the IL-12/IL-23-IFN-gamma axis. Patients with unexplained deep fungal infections, such as PCM, should be tested for defects in the IL-12/IL-23-IFN-gamma axis.