Andeen Nicole K, Kung Vanderlene L, Robertson Josh, Gurley Susan B, Avasare Rupali S, Sitaraman Sneha
Department of Pathology and Laboratory Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Division of Nephrology and Hypertension, Department of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
Glomerular Dis. 2022 Jun 16;2(4):164-175. doi: 10.1159/000525542. eCollection 2022.
Fibrillary glomerulonephritis (FGN) is found in approximately 1% of native kidney biopsies and was traditionally defined by glomerular deposition of fibrils larger than amyloid (12-24 nm diameter) composed of polyclonal IgG. Recent identification of DNAJB9 as a sensitive and specific marker of FGN has revolutionized FGN diagnosis and opened new avenues to studying FGN pathogenesis. In this review, we synthesize recent literature to provide an updated appraisal of the clinical and pathologic features of FGN, discuss diagnostic challenges and pitfalls, and propose molecular models of disease in light of DNAJB9.
DNAJB9 tissue assays, paraffin immunofluorescence studies, and IgG subclass testing demonstrate that FGN is distinct from other glomerular diseases with organized deposits and highlight FGN morphologic variants. Additionally, these newer techniques show that FGN is only rarely monoclonal, and patients with monoclonal FGN usually do not have a monoclonal gammopathy. mutation does not appear to affect the genetic architecture of FGN; however, the accumulation of DNAJB9 in FGN deposits suggests that disease is driven, at least in part, by proteins involved in the unfolded protein response. Treatments for FGN remain empiric, with some encouraging data suggesting that rituximab-based therapy is effective and that transplantation is a good option for patients progressing to ESKD.
DNAJB9 aids in distinguishing FGN from other glomerular diseases with organized deposits. Further investigations into the role of DNAJB9 in FGN pathogenesis are necessary to better understand disease initiation and progression and to ultimately develop targeted therapies.
纤维性肾小球肾炎（FGN）在约1%的原发性肾活检中被发现，传统上通过由多克隆IgG组成的大于淀粉样蛋白（直径12 - 24nm）的纤维在肾小球沉积来定义。最近将DNAJB9鉴定为FGN的敏感且特异的标志物，彻底改变了FGN的诊断，并为研究FGN发病机制开辟了新途径。在本综述中，我们综合近期文献，对FGN的临床和病理特征进行更新评估，讨论诊断挑战和陷阱，并根据DNAJB9提出疾病的分子模型。
DNAJB9组织检测、石蜡免疫荧光研究和IgG亚类检测表明，FGN与其他具有有组织沉积物的肾小球疾病不同，并突出了FGN的形态学变异。此外，这些新技术表明FGN很少是单克隆的，单克隆FGN患者通常没有单克隆丙种球蛋白病。突变似乎不影响FGN的遗传结构；然而，DNAJB9在FGN沉积物中的积累表明，该疾病至少部分是由参与未折叠蛋白反应的蛋白质驱动的。FGN的治疗仍然是经验性的，一些令人鼓舞的数据表明基于利妥昔单抗的治疗是有效的，并且对于进展为终末期肾病（ESKD）的患者，移植是一个不错的选择。
DNAJB9有助于将FGN与其他具有有组织沉积物的肾小球疾病区分开来。有必要进一步研究DNAJB9在FGN发病机制中的作用，以更好地理解疾病的起始和进展，并最终开发靶向治疗方法。
