Suzuki H, Suzuki Y, Aizawa M, Yamanaka T, Kihara M, Pang H, Horikoshi S, Tomino Y
Division of Nephrology, Department of Internal Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Kidney Int. 2007 Aug;72(3):319-27. doi: 10.1038/sj.ki.5002300. Epub 2007 May 9.
IgA nephropathy is the most common form of progressive glomerulonephritis although the pathophysiology of this nephropathy is unclear. The ddY mouse is a spontaneous animal model with variable incidence and extent of glomerular injury mimicking human IgA nephropathy. Here, we transplanted bone marrow cells from 20-week-old ddY mice with beginning or quiescent IgA nephropathy into irradiated similar ddY mice, C57Bl/6 (Th1 prone) mice, or BALB/c (Th2 prone) mice. Serum IgA/IgG complex and Th1/Th2 polarization of spleen cells was determined by enzyme-linked immunosorbent assay and confirmed by fluorescent cytometric analysis. The ddY mice with commencing IgA nephropathy demonstrated strong polarization toward Th1, while those with quiescent disease were Th2 polarized. Serum levels of IgA/IgG2a immune complex significantly correlated with the severity of the glomerular lesions. Bone marrow taken from mice with commencing IgA nephropathy conferred IgA nephropathy with Th1 polarization in recipient-quiescent mice, while transplantation from the quiescent mice ablated glomerular injury and mesangial IgA/IgG deposition in those commencing IgA disease. However, adoptive transfer of CD4(+) T cells from those whose disease began failed to induce any IgA deposition or renal injury. Our study suggests that bone marrow cells, presuming IgA producing cells, may initiate this disease. Th1 cells may be involved in the pathophysiology of the disease after glomerular IgA deposition.
IgA肾病是进行性肾小球肾炎最常见的形式，尽管这种肾病的病理生理学尚不清楚。ddY小鼠是一种自发性动物模型，其肾小球损伤的发生率和程度各不相同，可模拟人类IgA肾病。在此，我们将患有初期或静止期IgA肾病的20周龄ddY小鼠的骨髓细胞移植到经辐射的同类型ddY小鼠、C57Bl/6（倾向于Th1）小鼠或BALB/c（倾向于Th2）小鼠体内。通过酶联免疫吸附测定法测定血清IgA/IgG复合物以及脾细胞的Th1/Th2极化，并通过荧光细胞分析进行确认。患有初期IgA肾病的ddY小鼠表现出强烈的向Th1极化，而患有静止期疾病的小鼠则向Th2极化。血清IgA/IgG2a免疫复合物水平与肾小球病变的严重程度显著相关。取自患有初期IgA肾病小鼠的骨髓使受体静止期小鼠发生Th1极化的IgA肾病，而来自静止期小鼠的移植则消除了患有初期IgA疾病小鼠的肾小球损伤和系膜IgA/IgG沉积。然而，将疾病已开始的小鼠的CD4(+) T细胞进行过继转移未能诱导任何IgA沉积或肾损伤。我们的研究表明，假定为产生IgA的细胞的骨髓细胞可能引发这种疾病。Th1细胞可能在肾小球IgA沉积后参与该疾病的病理生理学过程。
