Department of Nephrology, Nagoya University Graduate School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya, Aichi, 466-8550, Japan.
Department of Molecular Medicine and Metabolism, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
CEN Case Rep. 2023 Aug;12(3):323-328. doi: 10.1007/s13730-022-00759-2. Epub 2022 Dec 28.
Fibrillary glomerulonephritis (FGN), a rare disease is pathologically characterized by glomerular fibril accumulation ranging from 12 to 24 nm in diameter with negative Congo red staining. Recently, the identification of DnaJ homolog subfamily B member 9 (DNAJB9) as a highly sensitive and specific marker for FGN has revolutionized diagnosis of this disease. However, few recent studies have reported DNAJB9-negative glomerulonephritis with fibrillar deposits. As such, it remains unclear whether DNAJB9-negative cases can be considered equivalent to FGN. Here, we report the case of a 70-year-old woman who developed renal impairment and nephrotic-range proteinuria. Renal biopsy and pathological examination revealed focal glomerulonephritis with fibrocellular crescents. Immunofluorescence microscopy showed IgA-dominant deposition of polytypic IgG in the glomerulus. Electron microscopy revealed hump-like subepithelial electron dense deposits with fibrils of 15-25 nm in diameter. These findings were consistent with FGN; thus, Congo red and direct fast scarlet (DFS) staining, and immunohistochemistry for DNAJB9 were performed. In addition to negative Congo red/DFS/DNAJB9 staining, laser microdissection (LMD) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) resulted negative for DNAJB9, which is a highly sensitive and specific marker for FGN. The patient's renal function further declined, prompting administration of rituximab weekly for 2 weeks, similar to the treatment for FGN. This is a unique case of IgA-dominant glomerulonephritis with DNAJB9-negative fibrillar polytypic immunoglobulin deposits in the subepithelium, unlike previous DNAJB9-negative cases. Thus, DNAJB9-negative cases diagnosed based on accurate electron microscopic evaluation must be gathered, and LMD and LC-MS/MS must be used to analyze the organized fibrillar deposits to reveal the disease entity.
纤维状肾小球肾炎(FGN)是一种罕见疾病,其病理学特征为肾小球内直径为 12 至 24nm 的纤维样物质积聚,刚果红染色阴性。最近,发现 DnaJ 同源物亚家族 B 成员 9(DNAJB9)是 FGN 的高度敏感和特异标志物,这一发现彻底改变了该病的诊断。然而,最近的研究报告中很少有 DNAJB9 阴性的纤维状沉积物肾小球肾炎病例。因此,目前尚不清楚 DNAJB9 阴性病例是否可以被视为 FGN。在此,我们报告了一例 70 岁女性,因肾功能损害和肾病范围蛋白尿就诊。肾活检和病理检查显示局灶性肾小球肾炎伴纤维母细胞性新月体。免疫荧光显微镜检查显示肾小球内存在 IgA 主导的多克隆 IgG 沉积。电子显微镜检查显示驼峰样上皮下电子致密沉积物,伴 15-25nm 直径的纤维。这些发现与 FGN 一致;因此,进行了刚果红和直接快速猩红(DFS)染色以及 DNAJB9 免疫组化检查。除刚果红/DFS/DNAJB9 染色阴性外,激光微切割(LMD)和液相色谱-串联质谱(LC-MS/MS)结果也显示 DNAJB9 阴性,DNAJB9 是 FGN 的高度敏感和特异标志物。患者的肾功能进一步下降,提示每周给予利妥昔单抗治疗 2 周,类似于 FGN 的治疗方法。这是一例独特的 IgA 主导的肾小球肾炎,在亚上皮下有 DNAJB9 阴性的纤维状多克隆免疫球蛋白沉积,与之前报告的 DNAJB9 阴性病例不同。因此,必须收集基于准确电子显微镜评估诊断的 DNAJB9 阴性病例,并使用 LMD 和 LC-MS/MS 分析有组织的纤维状沉积物以揭示疾病实体。