Miller-Hjelle M A, Hjelle J T, Jones M, Mayberry W R, Dombrink-Kurtzman M A, Peterson S W, Nowak D M, Darras F S
Department of Biomedical and Therapeutic Sciences, University of Illinois College of Medicine at Peoria 61656, USA.
Emerg Infect Dis. 1997 Apr-Jun;3(2):113-27. doi: 10.3201/eid0302.970204.
Polycystic kidney disease (PKD) is one of the most common genetic diseases in humans. We contend that it may be an emerging infectious disease and/or microbial toxicosis in a vulnerable human subpopulation. Use of a differential activation protocol for the Limulus amebocyte lysate (LAL) assay showed bacterial endotoxin and fungal (1-->3)-beta-D-glucans in cyst fluids from human kidneys with PKD. Fatty acid analysis of cyst fluid confirmed the presence of 3-hydroxy fatty acids characteristic of endotoxin. Tissue and cyst fluid from three PKD patients were examined for fungal components. Serologic tests showed Fusarium, Aspergillus, and Candida antigens. IgE, but not IgG, reactive with Fusarium and Candida were also detected in cyst fluid. Fungal DNA was detected in kidney tissue and cyst fluid from these three PKD patients, but not in healthy human kidney tissue. We examine the intertwined nature of the actions of endotoxin and fungal components, sphingolipid biology in PKD, the structure of PKD gene products, infections, and integrity of gut function to establish a mechanistic hypothesis for microbial provocation of human cystic disease. Proof of this hypothesis will require identification of the microbes and microbial components involved and multifaceted studies of PKD cell biology.
多囊肾病（PKD）是人类最常见的遗传疾病之一。我们认为，在一个易患人群中，它可能是一种新发传染病和/或微生物中毒。对鲎试剂（LAL）检测采用差异激活方案，结果显示PKD患者肾脏囊肿液中存在细菌内毒素和真菌（1→3）-β-D-葡聚糖。囊肿液的脂肪酸分析证实了内毒素特有的3-羟基脂肪酸的存在。对三名PKD患者的组织和囊肿液进行了真菌成分检测。血清学检测显示有镰刀菌、曲霉菌和念珠菌抗原。在囊肿液中还检测到与镰刀菌和念珠菌反应的IgE，但未检测到IgG。在这三名PKD患者的肾脏组织和囊肿液中检测到真菌DNA，但在健康人肾脏组织中未检测到。我们研究内毒素和真菌成分作用的交织性质、PKD中的鞘脂生物学、PKD基因产物的结构、感染以及肠道功能的完整性，以建立微生物引发人类囊性疾病的机制假说。要证明这一假说，需要鉴定所涉及的微生物和微生物成分，并对PKD细胞生物学进行多方面研究。
