Early-Childhood Membranous Nephropathy Due to Cationic Bovine Serum Albumin
Early-Childhood Membranous Nephropathy Due to Cationic Bovine Serum Albumin
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DOI：
10.1056/nejmoa1013792
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发表时间：
2011-06-02
影响因子：
158.5
通讯作者：
Ronco, Pierre
中科院分区：
文献类型：
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作者：
Debiec, Hanna;Lefeu, Florence;Ronco, Pierre
背景M型磷脂酶A（2）受体（PLA（2）R）最近被鉴定为70%的特发性膜性肾病（一种常见的肾病综合征）的候选抗原。其他特发性和继发性膜性肾病的抗原的性质仍不清楚。MethodsWe寻找抗体对牛血清白蛋白和循环牛血清白蛋白酶联免疫吸附试验和蛋白质印迹法从50例膜性肾病和172对照血清标本。采用十二烷基硫酸钠-聚丙烯酰胺凝胶双向电泳技术，对从血清标本中获得的免疫纯化循环牛血清白蛋白的性质进行了分析。我们检测到牛血清白蛋白在肾小球存款和分析洗脱IgG.Results11例，包括4名儿童的反应，有高水平的循环抗牛血清白蛋白抗体的IgG 1和IgG 4亚类。这些患者的循环牛血清白蛋白水平也升高，而循环免疫复合物水平没有增加。牛血清白蛋白免疫纯化的血清标本，这四个孩子迁移在pH值的基本范围内，而牛血清白蛋白从成人患者迁移在中性区域的天然牛血清白蛋白。仅在阳离子循环牛血清白蛋白和牛血清白蛋白特异性抗体均高水平的儿童中，在上皮下免疫沉积物中检测到牛血清白蛋白，并且在PLA（2）R缺失的情况下，它与IgG共定位。IgG从这样的存款是特定的牛血清albumin.ConclusionsSome儿童膜性肾病患者循环阳离子牛血清白蛋白和抗牛血清白蛋白抗体。牛血清白蛋白存在于免疫沉积物中，表明阳离子牛血清白蛋白通过与阴离子肾小球毛细血管壁结合并原位形成免疫复合物而具有致病性，如实验模型所示。
BackgroundThe M-type phospholipase A(2) receptor (PLA(2)R) was recently identified as a candidate antigen in 70% of cases of idiopathic membranous nephropathy, a common form of the nephrotic syndrome. The nature of antigens involved in other idiopathic and secondary membranous nephropathies remains unclear.MethodsWe searched for antibodies against bovine serum albumin and circulating bovine serum albumin by means of enzyme-linked immunosorbent assay and Western blotting in serum specimens obtained from 50 patients with membranous nephropathy and 172 controls. The properties of immunopurified circulating bovine serum albumin obtained from serum specimens were analyzed with the use of two-dimensional sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. We detected bovine serum albumin in glomerular deposits and analyzed the reactivity of eluted IgG.ResultsEleven patients, including four children, had high levels of circulating anti-bovine serum albumin antibodies, of both the IgG1 and IgG4 subclasses. These patients also had elevated levels of circulating bovine serum albumin, without an increase in circulating immune complex levels. Bovine serum albumin immunopurified from the serum specimens of these four children migrated in the basic range of pH, whereas the bovine serum albumin from adult patients migrated in neutral regions as native bovine serum albumin. Bovine serum albumin was detected in subepithelial immune deposits only in the children with both high levels of cationic circulating bovine serum albumin and bovine serum albumin-specific antibodies, and it colocalized with IgG in the absence of PLA(2)R. IgG eluted from such deposits was specific for bovine serum albumin.ConclusionsSome patients with childhood membranous nephropathy have both circulating cationic bovine serum albumin and anti-bovine serum albumin antibodies. Bovine serum albumin is present in immune deposits, suggesting that cationic bovine serum albumin is pathogenic through binding to the anionic glomerular capillary wall and in situ formation of immune complexes, as shown in experimental models.