Masai R, Wakui H, Komatsuda A, Togashi M, Maki N, Ohtani H, Oyama Y, Sawada K
Third Department of Internal Medicine, Akita University School of Medicine, Japan.
Clin Nephrol. 2009 Jul;72(1):46-54. doi: 10.5414/cnp72046.
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) associated with membranoproliferative features is an extremely rare entity. Information on clinicopathological features and prognosis in this entity is limited.
We reviewed 5,443 renal biopsies processed at our department, and identified 4 patients with PGNMID associated with membranoproliferative features. We evaluated clinicopathological features and outcomes in these patients, and characterized paraprotein deposits by immunofluorescence studies.
Three out of 4 patients had nephrotic syndrome with renal insufficiency at presentation. Cryoglobulin or monoclonal protein in serum and urine was not detected. Renal biopsy showed membranoproliferative features with or without nodular formation. Tubulointerstitial and vascular alterations were mild in three patients. All patients had glomerular IgG-kappa deposits. Heavy chain subclass analysis performed in 3 patients showed IgG3 deposits. Immunofluorescence studies using antibodies specific for gamma-heavy chain C(H)1, C(H)2, and C(H)3 domains and gamma3 hinge did not show any apparent deletion. Confocal microscopy revealed glomerular colocalization of light and heavy chains. On electron microscopy, granular deposits were predominantly mesangial and subendothelial. All patients were treated with steroids and cytotoxic agents, but no effect on proteinuria was observed. The renal outcome was progressive in all patients. Early death was observed in two elder patients. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 43 months).
Our study suggests a predominance of IgG3-kappa glomerular deposits of nondeleted whole immunoglobulin molecules in PGNMID associated with membranoproliferative features. The clinical outcome in patients with this entity appears to be poor.
伴有膜增生性特征的单克隆IgG沉积增生性肾小球肾炎（PGNMID）是一种极其罕见的疾病。关于该疾病临床病理特征及预后的信息有限。
我们回顾了在本部门处理的5443例肾活检病例，确定了4例伴有膜增生性特征的PGNMID患者。我们评估了这些患者的临床病理特征及预后，并通过免疫荧光研究对副蛋白沉积进行了特征分析。
4例患者中有3例在就诊时患有肾病综合征并伴有肾功能不全。未检测到血清和尿液中的冷球蛋白或单克隆蛋白。肾活检显示有或无结节形成的膜增生性特征。3例患者的肾小管间质和血管改变较轻。所有患者均有肾小球IgG-κ沉积。对3例患者进行的重链亚类分析显示为IgG3沉积。使用针对γ重链C(H)1、C(H)2和C(H)3结构域以及γ3铰链的特异性抗体进行的免疫荧光研究未显示任何明显缺失。共聚焦显微镜显示轻链和重链在肾小球中共定位。电子显微镜检查显示颗粒状沉积物主要位于系膜和内皮下。所有患者均接受了类固醇和细胞毒性药物治疗，但未观察到蛋白尿有改善。所有患者的肾脏预后均呈进行性。2例老年患者早期死亡。在就诊时或随访过程中（平均43个月），没有患者患有明显的骨髓瘤或淋巴瘤。
我们的研究表明，在伴有膜增生性特征的PGNMID中，未缺失的完整免疫球蛋白分子的IgG3-κ肾小球沉积占主导。该疾病患者的临床预后似乎较差。
