Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO-ANCA-associated glomerulonephritis
Immunopathologic co-localization of MPO, IgG, and C3 in glomeruli in human MPO-ANCA-associated glomerulonephritis
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DOI：
10.5414/cn107675
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发表时间：
2013-04-01
影响因子：
1.1
通讯作者：
Yamada, Akira
中科院分区：
文献类型：
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作者：
Kawashima, Soko;Arimura, Yoshihiro;Yamada, Akira
髓过氧化物酶抗中性粒细胞胞浆抗体（MPO ANCA）相关性肾小球肾炎（GN）是一种以少免疫性坏死性肾小球肾炎（NGN）为特征的疾病。尽管人们认为MPO-ANCA通过激活中性粒细胞参与了NGN中毛细血管损伤的发病机制，但最近的研究表明其他因素如肾小球上沉淀的免疫球蛋白可能起作用。在此，我们进行了一项病理学研究，探讨MPO，IgG，补体沉积的MPO阳性细胞和肾小球毛细血管在人类MPO ANCA相关的UN的关系。分析了20例MPO-ANCA相关性UN患者的317个肾小球标本。所有标本均显示IgG明显的局灶性节段性沉积。在节段性和整体性NCG的活动性病变中，MPO阳性细胞沿着肾小球浸润并伴有细胞外MPO沉积，邻近区域CD 34染色减少。IgG沉积物几乎与C3共定位，部分与MPO共定位，这也与CD 34染色减少有关，表明免疫复合物形成和由此产生的毛细血管损伤。MPO、IgG和C3的共定位仅见于轻度活动性肾小球病变。这些结果提示，不仅中性粒细胞释放的MPO本身，而且MPO与抗MPO抗体组成的免疫复合物在肾小球损伤中可能起一定的作用，尤其是在人MPO-ANCA相关性UN的早期。
Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated glomerulonephritis (GN) is characterized by pauci-immune necrotizing glomerulonephritis(NGN). Although it has been thought that MPO-ANCA is involved in the pathogenesis of capillary injuries in NGN via activation of neutrophils, recent studies suggest a possible role of other factors such as immunoglobulins precipitated on the glomeruli. Here we performed a pathological study investigating a relationship of deposition of MPO, IgG, complements with regard to MPO-positive cells and glomerular capillaries in human MPO-ANCA-associated UN. Renal specimen including 317 glomeruli obtained from 20 patients with MPO-ANCA-associated UN were analyzed. All of the specimens showed significant focal segmental deposition of IgG. There was a significant glomerular infiltration of MPO-positive cells along with deposition of extracellular MPO in the active lesions of segmental and global NCG, with CD34 staining being decreased in the adjacent areas. IgG deposits were almost colocalized with C3 and partly with MPO, which are also associated with a decrease in CD34 staining, suggesting that immune complex formation and the resultant capillary injuries. Actually occurred, the co-localization of MPO, IgG and C3 was seen only in the glomerular lesions with low severity and activity. These results suggest that not only MPO itself released from the neutrophils but also immune complexes composed of MPO and anti-MPO antibody may play some pathogenetic roles for the glomerular injuries especially in the early phase of human MPO-ANCA-associated UN.