Neumann Irmgard, Birck Rainer, Newman Mark, Schnülle Peter, Kriz Wilhelm, Nemoto Kyuichi, Yard Benito, Waldherr Rüdiger, Van Der Woude Fokko J
Fifth Department of Medicine, University Hospital Mannheim, Mannheim, Germany.
Kidney Int. 2003 Jul;64(1):140-8. doi: 10.1046/j.1523-1755.2003.00061.x.
Spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mice spontaneously develop crescentic glomerulonephritis (CGN), systemic vasculitis, and perinuclear ANCA (pANCA), and have been suggested as an animal model for human antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AASV). Since no systematic serologic, immunohistologic, or structural evaluation had been performed thus far, we reinvestigated the development of ANCA and CGN in these mice.
SCG/Kj mice were subjected to serologic and urinary analysis, as well as histologic evaluation of the kidneys by standard light, immunofluorescence, and electron microscopy at regular intervals during the course of the disease.
Perinuclear ANCA developed as early as the 6th week of life, increasing both in frequency and titer in up to 100% of animals at week 20. Crescent formation began at week 10 and peaked at week 16, maximally affecting 57% of glomeruli. Crescent formation was initiated by "activated" podocytes that formed cell bridges between tuft and Bowman's capsule. The typical picture of a diffuse immune complex nephritis was found in all animals as early as 8 weeks. Fluorescence intensity increased with age and became strongly positive for immunoglobulin (Ig)A, IgM, IgG, and C3 in the mesangium and along the peripheral capillary loops.
Although ANCAs were found in the majority of animals, the massive presence of glomerular immune deposits differed from the pauci-immune pattern found in human AASV, making this model not completely representative for human ANCA-associated CGN. However, the spontaneous and concomitant development of pANCA, small vessel vasculitis, and CGN raises the opportunity to analyze pathogenetic links between these disease manifestations in vivo.
自发形成新月体性肾小球肾炎的金尾（SCG/Kj）小鼠会自发发展为新月体性肾小球肾炎（CGN）、系统性血管炎和核周抗中性粒细胞胞浆抗体（pANCA），并且已被提议作为人类抗中性粒细胞胞浆抗体（ANCA）相关血管炎（AASV）的动物模型。由于迄今为止尚未进行系统的血清学、免疫组织学或结构评估，我们重新研究了这些小鼠中ANCA和CGN的发展情况。
在疾病过程中，定期对SCG/Kj小鼠进行血清学和尿液分析，以及通过标准光学显微镜、免疫荧光和电子显微镜对肾脏进行组织学评估。
核周ANCA最早在出生后第6周出现，在第20周时，高达100%的动物其出现频率和滴度均有所增加。新月体形成始于第10周，并在第16周达到峰值，最大累及57%的肾小球。新月体形成由在肾小球毛细血管丛和鲍曼囊之间形成细胞桥的“活化”足细胞引发。早在8周时，在所有动物中均发现了弥漫性免疫复合物肾炎的典型表现。荧光强度随年龄增长而增加，系膜区和外周毛细血管袢处的免疫球蛋白（Ig）A、IgM、IgG和C3呈强阳性。
尽管在大多数动物中发现了ANCA，但肾小球免疫沉积物的大量存在与人类AASV中发现的寡免疫模式不同，这使得该模型不能完全代表人类ANCA相关的CGN。然而，pANCA、小血管血管炎和CGN的自发且同时出现为在体内分析这些疾病表现之间的发病机制联系提供了机会。
