INSERM, Unite Mixte de Recherche Scientifique 702, Université Pierre et Marie Curie, Paris 6, Assistance Publique-Hôpitaux de Paris, Tenon Hospital, Paris, France.
N Engl J Med. 2011 Jun 2;364(22):2101-10. doi: 10.1056/NEJMoa1013792.
The 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.
We 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.
Eleven 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.
Some 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.
M 型磷脂酶 A（2）受体（PLA（2）R）最近被鉴定为 70%特发性膜性肾病（一种常见的肾病综合征形式）病例中的候选抗原。涉及其他特发性和继发性膜性肾病的抗原性质仍不清楚。
我们通过酶联免疫吸附试验和 Western 印迹法在 50 例膜性肾病患者和 172 例对照者的血清标本中寻找针对牛血清白蛋白和循环牛血清白蛋白的抗体。使用二维十二烷基硫酸钠-聚丙烯酰胺凝胶电泳分析从血清标本中免疫纯化的循环牛血清白蛋白的特性。我们检测了肾小球沉积物中的牛血清白蛋白并分析了洗脱 IgG 的反应性。
11 例患者，包括 4 例儿童，循环抗牛血清白蛋白抗体水平升高，包括 IgG1 和 IgG4 亚类。这些患者也有循环牛血清白蛋白水平升高，而循环免疫复合物水平没有增加。从这 4 例儿童的血清标本中免疫纯化的牛血清白蛋白在碱性 pH 值范围内迁移，而成年患者的牛血清白蛋白则以天然牛血清白蛋白的中性区域迁移。只有在高水平阳离子循环牛血清白蛋白和牛血清白蛋白特异性抗体的儿童中，才能在亚上皮免疫沉积物中检测到牛血清白蛋白，并且在没有 PLA（2）R 的情况下与 IgG 共定位。从这些沉积物中洗脱的 IgG 特异性针对牛血清白蛋白。
一些儿童膜性肾病患者既有循环阳离子牛血清白蛋白又有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，这在实验模型中得到了证实。
