Oren R, Laufer J, Goldberg I, Kopolovic J, Waldherr R, Passwell J H
Samuel Jared Kushnick Pediatric Immunology Laboratory, Sheba Medical Center, Sackler School of Medicine, Tel Aviv University, Israel.
Immunology. 1995 Dec;86(4):575-83.
The deposition of complement in the kidney mesangium is a constant finding associated with renal injury in IgA nephropathy, even though IgA does not bind complement. We have previously reported that complement gene expression in the kidney increases concurrently with the progression of immune complex disease in murine lupus nephritis. We have now studied the expression of C3, C4, factor B and HLA-DR alpha mRNA by in situ hybridization in renal biopsy specimens of patients with IgA nephropathy and compared these findings to those in patients with other immune-mediated diseases of the kidney, hereditary nephritis and normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the renal tubular epithelial cells, while no expression of either C3 or factor B mRNA was apparent in the glomerulus. Specimens from patients with other immune-mediated forms of chronic glomerulonephritis also showed a similar pattern of expression of C3 and factor B mRNA only in the tubules, but not in the glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue or biopsy specimens from patients with hereditary nephritis. C4 mRNA was expressed in the tubular epithelial cells in all specimens examined, indicating that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy HLA-DR alpha mRNA was observed in the interstitium, but not the tubules or glomerular cells. In contrast, HLA-DR alpha mRNA was present in the glomerulus and scattered in the interstitium in other immune-mediated kidney diseases. There was no expression of HLA-DR alpha mRNA in hereditary nephritis or normal kidney. Our findings, which reflect the immunopathogenic events in vivo, provide new insights as to the interpretation of the molecular immunology of this immune complex disease.
补体在肾脏系膜中的沉积是IgA肾病肾损伤的一个常见表现，尽管IgA并不结合补体。我们之前报道过，在小鼠狼疮性肾炎中，肾脏中补体基因表达随免疫复合物疾病的进展而同步增加。我们现在通过原位杂交研究了IgA肾病患者肾活检标本中C3、C4、B因子和HLA-DRα mRNA的表达，并将这些结果与其他免疫介导的肾脏疾病、遗传性肾炎和正常肾脏患者的结果进行了比较。在IgA肾病中，C3和B因子mRNA在肾小管上皮细胞中表达，而在肾小球中未观察到C3或B因子mRNA的表达。其他免疫介导形式的慢性肾小球肾炎患者的标本也显示，C3和B因子mRNA仅在肾小管中表达，而在肾小球中不表达。然而，在正常肾脏组织或遗传性肾炎患者的活检标本中未发现C3和B因子mRNA。在所有检查的标本中，C4 mRNA均在肾小管上皮细胞中表达，表明C4 mRNA在人肾脏中组成性表达。在IgA肾病中，HLA-DRα mRNA在间质中观察到，但在肾小管或肾小球细胞中未观察到。相比之下，在其他免疫介导的肾脏疾病中，HLA-DRα mRNA存在于肾小球中，并散在于间质中。在遗传性肾炎或正常肾脏中未发现HLA-DRα mRNA的表达。我们的发现反映了体内的免疫致病事件，为解释这种免疫复合物疾病的分子免疫学提供了新的见解。
