Oregon Health & Science University, Department of Pathology.
Department of Medicine, Division of Nephrology and Hypertension, Portland, Oregon, USA.
Curr Opin Nephrol Hypertens. 2021 May 1;30(3):294-302. doi: 10.1097/MNH.0000000000000706.
Fibrillary glomerulonephritis (FGN) involves ∼1% of native kidney biopsies and is characterized by glomerular deposition of fibrils larger than amyloid (12-24 nm diameter) composed of polyclonal immunoglobulin G (IgG). The recent discovery of DNA J homolog subfamily B member 9 (DNAJB9) in FGN glomerular deposits has contributed a specific and sensitive biomarker, informing morphologic classification and pathogenesis. This review will consider contemporary FGN incidence and genetics, pathogenesis, (lack of) paraprotein association, variants, treatment, and transplantation.
DNAJB9 tissue assays have enabled the identification of morphologic variants and improved classification of fibrillary-like glomerular diseases. Together with paraffin immunofluorescence and IgG subclass studies, these have established that FGN is only rarely monoclonal and these patients usually do not have an monoclonal gammopathy. The discovery of DNAJB9 opens new avenues of investigation into FGN pathogenesis, especially those of the unfolded protein response. Treatment for FGN remains empiric, with some encouraging data on rituximab-based therapy. Transplantation is a good option for patients progressing to end-stage kidney disease.
Advances building on the discovery of DNAJB9 in FGN should lead to long-term evolution in targeted treatment and outcome of this glomerular disease.
纤维状肾小球肾炎（FGN）累及约 1%的原发性肾脏活检，其特征是肾小球中沉积有直径大于淀粉样物质（12-24nm）的纤维，由多克隆免疫球蛋白 G（IgG）组成。最近在 FGN 肾小球沉积物中发现的 DNAJ 同源物亚家族 B 成员 9（DNAJB9）提供了一个特异性和敏感的生物标志物，有助于形态分类和发病机制。本综述将考虑当代 FGN 的发病率和遗传学、发病机制、（缺乏）副蛋白相关性、变体、治疗和移植。
DNAJB9 组织检测使鉴定形态变体和改善纤维状肾小球疾病的分类成为可能。与石蜡免疫荧光和 IgG 亚类研究一起，这些研究确立了 FGN 很少是单克隆的，这些患者通常没有单克隆丙种球蛋白病。DNAJB9 的发现为 FGN 的发病机制开辟了新的研究途径，特别是 unfolded protein response 的研究途径。FGN 的治疗仍然是经验性的，基于利妥昔单抗的治疗有一些令人鼓舞的数据。对于进展为终末期肾病的患者，移植是一个很好的选择。
基于 DNAJB9 在 FGN 中的发现的进展，应该会导致针对这种肾小球疾病的靶向治疗和预后的长期演变。
