Department of Nephrology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.
Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.
Kidney Blood Press Res. 2020;45(5):713-726. doi: 10.1159/000508665. Epub 2020 Sep 7.
Co-deposition of mannose-binding lectin (MBL) and IgG4 anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies under subepithelial cells has been observed in patients with idiopathic membranous nephropathy (iMN), but the relationships of MBL deposition to iMN severity and progression remain unclear.
Patients diagnosed with iMN who underwent renal puncture were enrolled and followed up for a median of 17 months (interquartile range [IQR], 9-25 months). Serum anti-PLA2R and anti-thrombospondin type-1 domain-containing 7A antibodies and MBL were detected by ELISA. Glomerular MBL and anti-PLA2R antibodies were detected by immunofluorescence. Proteinuria remission, including complete remission (CR), was defined as a clinical event. Clinicopathological characteristics and kidney outcomes were compared between patients with and without MBL deposition.
In 67 prevalent patients with biopsy-proven iMN, serum anti-PLA2R antibodies and anti-THSD7A antibodies were present in 37 (55.3%) and 1 (1.4%) patient with iMN. The positivity of glomerular MBL deposition and tissue anti-PLA2R antibody was 53 (79.1%) and 49 (73.1%), respectively. No significant difference was found between the MBL-positive and negative groups in the albumin level (26.5 ± 6.6 and 28.6 ± 6.1 g/L), eGFR (104.8 ± 17.4 and 114.6 ± 16.1 mL/min/1.73 m2), 24-h proteinuria (5.35 and 4.25 g/day), or serum MBL level corrected by serum Cr 4.92 (IQR, 0.86, 8.90) and 2.28 (IQR, 0.4, 5.62). In a Cox proportional hazards regression model adjusted for sex, age, systolic blood pressure, eGFR, immunosuppressive agent use, 24-h proteinuria, and anti-PLA2R antibody concentration, glomerular MBL deposition was independently associated with ICR of proteinuria (HR, 6.31; 95% CI, 1.1-36.1; p = 0.039).
The MBL pathway of complement activation is commonly initiated in patients with iMN, and patients with MBL deposition reach ICR faster than patients without MBL deposition.
在特发性膜性肾病（iMN）患者的上皮下细胞下观察到甘露糖结合凝集素（MBL）和 IgG4 抗磷脂酶 A2 受体（抗-PLA2R）自身抗体的共沉积，但 MBL 沉积与 iMN 严重程度和进展的关系尚不清楚。
招募了接受肾活检诊断为 iMN 且接受随访的患者，中位随访时间为 17 个月（四分位距[IQR]，9-25 个月）。通过 ELISA 检测血清抗-PLA2R 和抗血栓素-1 型结构域包含 7A 抗体和 MBL。通过免疫荧光法检测肾小球 MBL 和抗-PLA2R 抗体。蛋白尿缓解（包括完全缓解[CR]）定义为临床事件。比较有和无 MBL 沉积患者的临床病理特征和肾脏结局。
在 67 例经活检证实的 iMN 患者中，37 例（55.3%）患者的血清抗-PLA2R 抗体和 1 例（1.4%）患者的抗 THSD7A 抗体呈阳性。肾小球 MBL 沉积和组织抗-PLA2R 抗体的阳性率分别为 79.1%（53 例）和 73.1%（49 例）。MBL 阳性组和阴性组的白蛋白水平（26.5±6.6 和 28.6±6.1 g/L）、eGFR（104.8±17.4 和 114.6±16.1 mL/min/1.73 m2）、24 小时蛋白尿（5.35 和 4.25 g/天）或血清 MBL 水平（血清 Cr 校正后，4.92（IQR，0.86，8.90）和 2.28（IQR，0.4，5.62））无显著差异。在调整性别、年龄、收缩压、eGFR、免疫抑制剂使用、24 小时蛋白尿和抗-PLA2R 抗体浓度的 Cox 比例风险回归模型中，肾小球 MBL 沉积与蛋白尿 ICR 独立相关（HR，6.31；95%CI，1.1-36.1；p=0.039）。
补体激活的 MBL 途径在 iMN 患者中通常被启动，并且 MBL 沉积的患者比无 MBL 沉积的患者更快达到 ICR。
