Pardo V, Strauss J, Kramer H, Ozawa T, McIntosh R M
Am J Med. 1975 Nov;59(5):650-9. doi: 10.1016/0002-9343(75)90226-0.
A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.
多种肾脏结构和功能异常与镰状细胞病相关。为明确血红蛋白病与肾小球疾病之间的关系，对7例有肾小球疾病临床和实验室证据的患者进行了临床病理相关性、肾脏形态学、超微结构免疫组织学及功能研究。此外，还进行了免疫学研究，包括分离和鉴定可冷沉淀免疫复合物、测定免疫球蛋白、总补体和补体成分水平以及针对几种抗原的抗体滴度，以试图明确肾脏疾病的病因和发病机制及其与镰状细胞贫血的关系。所有患者均有蛋白尿。半数以上患者出现肾病综合征、高血压、血尿和肾功能不全。所有患者均有不同程度的膜增生性肾小球肾炎；肾小球基底膜分裂、肾小球内电子致密沉积物；间质纤维化、肾小管萎缩和含铁血黄素沉积常见。通过这些方法研究的所有患者中，免疫球蛋白补体成分（经典补体途径）和肾小管上皮抗原沿肾小球基底膜呈颗粒状分布。在部分患者的循环中检测到肾小管上皮抗原-抗肾小管上皮抗原的可冷沉淀复合物以及抗肾小管上皮抗原的抗体。没有替代补体途径激活的血清学证据。这些研究证实了与镰状细胞贫血相关的免疫沉积正常补体血症性肾炎；它们进一步支持了我们的假设，即这种关系不仅仅是巧合，而是由肾小管上皮抗原-抗肾小管上皮抗原的免疫复合物在肾小球沉积介导的，该抗原可能在继发于与镰状细胞病相关的氧合和血流动力学改变的肾小管损伤后释放。
