Da Yi, Goh Giap Hean, Lau Titus, Chng Wee Joo, Soekojo Cinnie Yentia
Division of Nephrology, Department of Medicine, National University Hospital, Singapore, Singapore.
Department of Pathology, National University Hospital, Singapore, Singapore.
Front Oncol. 2022 May 25;12:880923. doi: 10.3389/fonc.2022.880923. eCollection 2022.
Fibrillary glomerulonephritis (FGN) is a rare glomerular disease featured by the randomly arranged 12- to 24-nm fibrils under electron microscopy (EM). Up to 10% of FGN patients have monoclonal gammopathy. However, distinguishing between FGN as monoclonal gammopathy of renal significance (MGRS) and FGN from other causes with incidental monoclonal gammopathy of undetermined significance (MGUS) can be challenging, as the current way of demonstrating monoclonality is flawed due to (1) the suboptimal sensitivity of kappa staining by immunofluorescence in frozen tissue (IF-F) as compared to pronase-digested paraffin sections (IF-P), causing incorrect labeling of light chain restriction; (2) the unavailability of immunoglobulin G (IgG) subtyping in some centers; and (3) the unavailability of tests demonstrating the monoclonality of highly variable VH or VL domains in immunoglobulin structures in clinical use. The discovery of DnaJ homolog subfamily B member 9 (DNAJB9) allows diagnosis for FGN with less reliance on EM, and the summary of recent studies revealed that genuine MGRS is extremely rare among FGN. Further research integrating IF-P, IgG subtyping, VH or VL domain monoclonality confirmation, and DNAJB9 as diagnostic modalities, with corresponding clinical data including treatment response and prognosis, is required for a better understanding of this subject.
纤维性肾小球肾炎（FGN）是一种罕见的肾小球疾病，其特征是在电子显微镜（EM）下可见随机排列的12至24纳米纤维。高达10%的FGN患者存在单克隆丙种球蛋白病。然而，区分具有肾脏意义的单克隆丙种球蛋白病（MGRS）的FGN和伴有意义未明的偶然单克隆丙种球蛋白病（MGUS）的其他原因导致的FGN可能具有挑战性，因为目前证明单克隆性的方法存在缺陷，原因如下：（1）与经链霉蛋白酶消化的石蜡切片（IF-P）相比，冷冻组织免疫荧光（IF-F）中κ染色的敏感性欠佳，导致轻链限制标记错误；（2）一些中心无法进行免疫球蛋白G（IgG）亚型分析；（3）临床应用中缺乏能够证明免疫球蛋白结构中高度可变的VH或VL结构域单克隆性的检测方法。DnaJ同源亚家族B成员9（DNAJB9）的发现使得FGN的诊断减少了对EM的依赖，最近的研究总结表明，真正的MGRS在FGN中极为罕见。需要进一步整合IF-P、IgG亚型分析、VH或VL结构域单克隆性确认以及DNAJB9作为诊断方式，并结合包括治疗反应和预后在内的相应临床数据，以更好地理解这一主题。
