Immuno-pathological studies in IgA nephropathy : The role of virus for etiological and progressive factors

病毒被怀疑是IgA肾病的病原体。最近，在IgA肾病患者的肾组织中检测到病毒。我们试图通过将病毒接种到小鼠体内来引起类似于IgA肾病的病变，并通过原位杂交检测病变中的病毒RNA。1~5月龄小鼠每月静脉接种一次柯萨奇B_4病毒，6~12月龄每月处死一次。6个月龄肾小球系膜细胞增殖，光镜下可见高碘酸席夫染色阳性沉积，电子显微镜下可见电子致密沉积。肾小球系膜免疫球蛋白和免疫球蛋白A沉积呈阳性，10个月龄后以免疫球蛋白A沉积为主。原位杂交观察到柯萨奇B_4病毒在皮损中的信号。这些观察表明，柯萨奇B_4病毒反复接种小鼠可引起类似于IgA肾病的病变。病变的沉积可能是柯萨奇B4病毒的免疫复合体，这些免疫复合体损伤肾脏组织。反复感染知名病毒可引起小鼠非常类似于人类IgA肾病的病变。如果进一步的研究证实肾小球病变的早期形成和主要的IgA沉积，我们的实验模型可能有助于阐明人类IgA肾病的机制。

Viruses have been suspected to be etiological agents of IgA nephropathy. Recently, viruses were detected in renal tissues from patients with IgA nephropathy. We tried to cause lesions similar to IgA nephropathy by inoculating virus into mice and to detect virus RNA in the lesion by in situ hybridization. A group of mice were inoculated intravenously with coxsackie B_4 virus once a month from 1 to 5 months of age and sacrificed monthly from 6 to 12 months of age. Mesangial proliferation and deposits that stained positive with periodic acid-Schiff in light microscopy and electron-dense deposits in electron microscopy were found from 6 months of age. Positive findings for IgG and IgA deposition in the mesangium were noted and the intensity of IgA deposition was predominant after 10 months of age. The signals of coxsackie B_4 virus by in situ hybridization were observed in the lesions. These observations indicate that coxsackie B_4 virus inoculated repeatedly into mice induces lesions similar to IgA nephropathy. The depositions of the lesions may be immune complexes of coxsackie B_4 virus and these immune complexes injure renal tissues.Lesions very similar to human IgA nephropathy could be caused in mice by repeated infections of well-known virus. If further studies demonstrate an early from of glomerular lesions and a predominant deposition for IgA,our experimental model may be useful to clarify the mechanism of human IgA nephropathy.