National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
National Clinical Research Center of Kidney Diseases, Jinling Clinical Medical College of Nanjing Medical University, Nanjing, China.
J Clin Pathol. 2019 Jan;72(1):31-37. doi: 10.1136/jclinpath-2018-205278. Epub 2018 Oct 12.
To explore the clinicopathological characteristics of patients with anti-GBM antibody-negative anti-GBM disease.
The clinical and renal pathological findings were retrospectively studied in 19 patients. All patients met the following inclusion criteria: linear GBM IgG deposition on immunofluorescence(IF); and lack of serum anti-GBM antibodies by ELISA and indirect immunofluorescence assay.
There were 17 male and two female patients, with a median age of 36 years (range 15-61 years). Hypertension was present in 68% of cases, nephrotic-range proteinuria (> 3.5 g/24 hours) in 42%, nephrotic syndrome in 37%, microhaematuria in 95%, renal insufficiency in 63% and lung involvement in 16%. On biopsy all patients had linear GBM staining for polyclonal IgG by IF. The dominant IgG subtype was IgG4 or IgG1. By light microscopy, mesangial proliferative GN without crescents was seen in four patients; proliferative GN (mesangial proliferative GN in eight; endocapillary proliferative GN in two; and membranoproliferative GN in two) with crescents (focal in 11; diffuse in one) in 12 patients; and crescentic GN without mesangial or endocapillary proliferative or membranoproliferative changes in three patients. By electron microscopy, six patients showed scarce electron dense deposits in glomeruli and 11 patients had global podocyte effacement. Totally, 10 (53%) patients received immunosuppressive therapy. The median follow-up was 15 months and six (32%) patients progressed to end-stage renal disease.
Anti-GBM antibody-negative anti-GBM disease was different from classic anti-GBM disease clinically and pathologically. The pathogenesis of the renal injury in these patients has not been elucidated until now and it should be studied and identified further.
探讨抗肾小球基底膜（GBM）抗体阴性抗 GBM 病患者的临床病理特征。
回顾性研究了 19 例符合以下纳入标准的患者的临床和肾脏病理发现：免疫荧光（IF）检测线性 GBM IgG 沉积；酶联免疫吸附试验（ELISA）和间接免疫荧光法检测血清抗 GBM 抗体阴性。
17 例为男性，2 例为女性，中位年龄 36 岁（15-61 岁）。68%的患者存在高血压，42%的患者出现肾病范围蛋白尿（>3.5g/24 小时），37%的患者出现肾病综合征，95%的患者出现镜下血尿，63%的患者出现肾功能不全，16%的患者出现肺部受累。免疫荧光检查所有患者的 GBM 均呈线性 IgG 多克隆染色。优势 IgG 亚型为 IgG4 或 IgG1。光镜下，4 例患者表现为无新月体的系膜增生性肾小球肾炎；12 例患者表现为增生性肾小球肾炎（系膜增生性肾小球肾炎 8 例，毛细血管内增生性肾小球肾炎 2 例，膜增生性肾小球肾炎 2 例）伴新月体（局灶性 11 例，弥漫性 1 例）；3 例患者表现为无系膜、毛细血管内或膜增生性改变的新月体性肾小球肾炎。电镜下，6 例患者肾小球内电子致密物沉积稀少，11 例患者出现肾小球足细胞广泛消失。总共 10 例（53%）患者接受了免疫抑制治疗。中位随访时间为 15 个月，6 例（32%）患者进展至终末期肾病。
抗 GBM 抗体阴性抗 GBM 病在临床上和病理学上均不同于经典的抗 GBM 病。这些患者肾损伤的发病机制尚未阐明，需要进一步研究和鉴定。
