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。我们尝试用HBV感染小鼠，造成类似IgA肾病的病变，并用原位杂交技术检测病变中的病毒RNA。一组小鼠从1~5月龄开始每月静脉接种一次柯萨奇B_4病毒，从6~12月龄开始每月处死一次。从6月龄开始，在光镜下发现系膜增生和沉积物，高碘酸-希夫染色阳性，在电子显微镜下发现电子致密沉积物。IgG和IgA沉积在系膜中的阳性结果被注意到，IgA沉积的强度在10月龄后占主导地位。原位杂交结果显示病变组织中有柯萨奇B_4病毒信号。这些结果表明，柯萨奇B_4病毒反复接种小鼠可引起类似IgA肾病的病变。这些病变的沉积物可能是柯萨奇B_4病毒的免疫复合物，这些免疫复合物损伤肾组织。如果进一步的研究表明肾小球病变的早期形式和IgA的主要沉积，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.