Department of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, L235, Stanford, CA, 94305, USA.
Oakland University William Beaumont School of Medicine, Rochester, MI, USA.
Pediatr Nephrol. 2021 Apr;36(4):927-937. doi: 10.1007/s00467-020-04763-5. Epub 2020 Oct 12.
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a glomerular disease defined by non-organized glomerular deposits of heavy and light chain-restricted immunoglobulin and is rarely reported in children.
We characterized a series of nine pediatric patients from two academic centers with biopsy-proven PGNMID and additionally describe two patients with monotypic IgG in the setting of IgM deposition.
Each patient presented with hematuria and/or proteinuria; however, only five had elevated serum creatinine. Prodromal or concurrent infection was identified in six patients, low C3 in five, and alternate complement pathway gene variants in two. No monoclonal serum proteins were identified in five tested patients. Seven patients had monotypic deposits composed of IgG3-λ, two showed IgG3-κ, and one each IgG1 and IgG3 with lambda dominance in the setting of IgM deposition. The glomerular pattern was predominantly mesangial proliferative or membranoproliferative glomerulonephritis (MPGN). Treatment and outcomes were variable; four patients have recent PGNMID diagnoses and therefore minimal follow up, one had relatively stable kidney function for over a decade, and six experienced kidney failure, with four receiving transplants. Recurrent deposits of the same isotype were identified in five of six transplanted kidneys, corresponding to three of four transplanted patients. One of these patients developed PGNMID recurrences in three separate kidney allografts over a 20-year disease course.
Our study emphasizes the need for upfront IgG subclass investigation in pediatric mesangial or MPGN with IgG deposition and monotypic or biased light-chain staining. Furthermore, this pediatric experience suggests expanded pathogenic considerations in PGNMID. Graphical abstract.
伴有单克隆 IgG 沉积的增生性肾小球肾炎（PGNMID）是一种由重链和轻链受限免疫球蛋白无组织性肾小球沉积定义的肾小球疾病，在儿童中罕见报道。
我们对来自两个学术中心的 9 名经活检证实为 PGNMID 的儿科患者进行了特征描述，并另外描述了 2 名在 IgM 沉积背景下存在单克隆 IgG 的患者。
每位患者均表现为血尿和/或蛋白尿；然而，仅有 5 例患者的血清肌酐升高。6 例患者有前驱或同时感染，5 例患者 C3 降低，2 例患者交替补体途径基因变异。在 5 例检测的患者中未发现单克隆血清蛋白。7 例患者的单克隆沉积物由 IgG3-λ 组成，2 例显示 IgG3-κ，1 例各为 IgG1 和 IgG3，在 IgM 沉积背景下存在 λ 优势。肾小球模式主要为系膜增生性或膜增生性肾小球肾炎（MPGN）。治疗和结局各不相同；4 例患者最近诊断为 PGNMID，因此随访时间较短，1 例患者肾功能稳定超过 10 年，6 例患者发生肾衰竭，其中 4 例接受了移植。6 例移植肾中有 5 例均发现同种类型的沉积再次出现，4 例移植患者中有 3 例发生了同种类型的沉积再次出现。其中 1 例患者在 20 年的疾病过程中，在 3 个不同的同种异体肾移植中出现了 PGNMID 复发。
我们的研究强调了在儿童系膜或 MPGN 伴 IgG 沉积和单克隆或偏轻链染色时，需要进行 IgG 亚类的初步检查。此外，该儿科经验提示在 PGNMID 中需要扩展发病机制的考虑。
