Nasr Samih H, Markowitz Glen S, Goldstein Carl S, Fildes Robert D, D'Agati Vivette D
Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10023, USA.
Hum Pathol. 2006 May;37(5):547-54. doi: 10.1016/j.humpath.2005.12.017.
The defining ultrastructural features of hereditary nephritis are "basket weave" lamellation or thinning of glomerular basement membranes. Electron-dense deposits are not seen and immunofluorescence (IF) is generally negative. In this study, we report 5 cases of hereditary nephritis in which substantial amounts of glomerular electron-dense deposits were identified on electron microscopy, with corresponding positive IF staining in 4 cases, suggesting immune complex-mediated glomerulonephritis. However, no case had histological evidence of glomerular endocapillary or extracapillary proliferation or leukocyte infiltration typical of active glomerulonephritis. Four cases were diagnosed at outside institutions simply as forms of glomerulonephritis without considering the possibility of hereditary nephritis and were sent for consultation in contemplation of possible immunosuppressive therapy. All patients had negative serologies and no known underlying infectious or autoimmune disease; 4 patients had family history of hematuria or renal disease. The glomerular electron-dense deposits were predominantly mesangial (4 cases) and intramembranous (4 cases), as well as subepithelial (2 cases) or subendothelial (1 case). Corresponding IF positivity for immune reactants was identified in 4 cases, and IgG was the predominant immunoglobulin deposited. A characteristic feature was the tendency for deposits to form between the complex layers of glomerular basement membrane material, favoring a process of nonspecific entrapment of immune reactants within the thickened, lamellated basement membrane. In all cases, a diagnosis of hereditary nephritis was confirmed by demonstration of the characteristic loss of immunoreactivity for the alpha5 subunit of collagen IV (4 cases) or Goodpasture's antigen (1 case) in renal or epidermal basement membranes. These cases expand the spectrum of unusual pathological findings in hereditary nephritis and emphasize the potential for hereditary nephritis to mimic immune complex glomerulonephritis.
遗传性肾炎的决定性超微结构特征是肾小球基底膜呈“篮纹状”分层或变薄。未见电子致密沉积物，免疫荧光（IF）通常为阴性。在本研究中，我们报告了5例遗传性肾炎病例，这些病例在电子显微镜下发现了大量肾小球电子致密沉积物，4例相应的IF染色呈阳性，提示免疫复合物介导的肾小球肾炎。然而，没有病例具有活动性肾小球肾炎典型的肾小球毛细血管内或毛细血管外增生或白细胞浸润的组织学证据。4例在外部机构仅被诊断为肾小球肾炎的形式，未考虑遗传性肾炎的可能性，并因考虑可能的免疫抑制治疗而前来咨询。所有患者血清学检查均为阴性，且无已知的潜在感染或自身免疫性疾病；4例患者有血尿或肾病家族史。肾小球电子致密沉积物主要位于系膜区（4例）和膜内（4例），以及上皮下（2例）或内皮下（1例）。4例发现免疫反应物的相应IF阳性，IgG是沉积的主要免疫球蛋白。一个特征性表现是沉积物倾向于在肾小球基底膜物质的复杂层之间形成，有利于免疫反应物在增厚的、分层的基底膜内非特异性截留。在所有病例中，通过证明肾或表皮基底膜中IV型胶原α5亚基（4例）或Goodpasture抗原（1例）的免疫反应性特征性丧失，确诊为遗传性肾炎。这些病例拓宽了遗传性肾炎异常病理表现的范围，并强调了遗传性肾炎模拟免疫复合物性肾小球肾炎的可能性。
