Staphylococcus aureus antigens induce IgA-type glomerulonephritis in Balb/c mice

背景。金黄色葡萄球菌（金黄色葡萄球菌）是一种常见的正常和致病菌群，定植在粘膜组织上。我们之前报道过耐甲氧西林金黄色葡萄球菌感染期间发生的肾小球肾炎，表现为血清IgA和IgG水平的多克隆性升高和各种组织学表现，如系膜毛细血管外和毛细血管内增生。为了探讨金黄色葡萄球菌抗原的致病作用，我们用金黄色葡萄球菌衍生抗原免疫小鼠，诱导与人IgA肾病相似的IgA型肾小球肾炎。用金黄色葡萄球菌衍生抗原和Freund's不完全佐剂免疫BaIb/c小鼠（Th2优势型）和C57BL/6小鼠（Th1优势型），每两周免疫4个月。所有BaIb/c小鼠系膜增生性肾小球肾炎伴IgA、IgG和C3沉积。尽管在C57BL/6小鼠中也可见到C3沉积和系膜区域的细胞增殖，但它们与尿检结果无关。在BaIb/c小鼠中，用亲和纯化的人抗s抗体在肾小球中检测金黄色葡萄球菌抗原。C57BL/6小鼠体内无金黄色葡萄球菌抗体。使用的抗体与几种金黄色葡萄球菌抗原反应。经western blot分析，BaIb/c与C57BL/6的主要识别差异条带在30-35kDa左右。此外，与b6相比，BaIb/c中转化生长因子-β mRNA的表达增加。金黄色葡萄球菌抗原，特别是30-35kDa蛋白和宿主遗传背景可能在iga样肾小球肾炎的发病机制中起重要作用。

Background. Staphylococcus aureus (S. aureus) is a common normal and pathogenic flora that colonizes on mucosal tissues. We had earlier reported glomerulonephritis occurred during methicillin resistant S. aureus infection, that showed polyclonal elevation of serum IgA and IgG levels and various histological findings, such as mesangial extracapillary and endocapillary proliferation. To investigate pathogenic roles of S.aureus antigens we induced IgA-type glomerulonephritis in mice which is similar to human IgA nephropathy, by immunization of antigens derived from S. aureus.Methods. BaIb/c mice (Th2 dominant type) and C57BL/6 (Th1 dominant type) were immunized with antigens deriired from S. aureus with Freund's incomplete adiuvant biweekly for 4 months.Results. Mesangial proliferative glomerulonephritis with IgA, IgG and C3 depositions were observed in all BaIb/c mice. Although C3 depositioris and cell proliferation in the mesangial area were also seen in C57BL/6 mice, they were not correlated with urinary findings. In BaIb/c mice, S. aureus antigens were detected in glomeruli using affinity purified human anti-S. aureus antibodies, however there was no staining in C57BL/6 mice. The used antibodies reacted with several S. aureus antigens. by western blot analysis and the main band that was differently recognized between BaIb/c and C57BL/6 was around 30-35kDa. Moreover increased transforming growth factor-β mRNA expression was seen in BaIb/c compare to those in B6.Conclusions. S. aureus antigens, especially 30-35kDa protein and genetic background of hosts may play important roles in the pathogenesis of IgA-like glomerulonephritis.