Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, China.
Front Immunol. 2024 Jan 5;14:1297107. doi: 10.3389/fimmu.2023.1297107. eCollection 2023.
Idiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies. There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear.
Immunohistochemical staining of PLA2R, THSD7A, and NELL-1 was conducted on kidney tissue samples obtained from patients diagnosed with IMN. Simultaneously, the presence of corresponding serum antibodies was determined. Patients exhibiting positivity for dual antigens were included in the study, identified either through tissue staining or serum antibody detection. We retrospectively collected their clinical, pathological, and follow-up data and measured their serum antibody levels at multiple time points. Additionally, the same type of dual antigen-positive IMN cases reported in the literature were reviewed to extract clinical, pathological, and prognostic information. We compared the data for all of the above dual antigen-positive and PLA2R single-positive IMN cases at our center.
We identified 6 IMN patients with dual antigen positivity at our center, approximately 0.7% of whole MN series; the previous literature reports 43 IMN patients with dual antigen positivity, the proportion ranged from 0.2% to 2.8%. The IgG1 positivity rate in the renal tissue of the dual antigen-positive patients at our center was significantly lower than that of dual antigen-positive patients previously reported (16.7% vs. 100.0%, p=0.015), but there was no significant difference in clinical or prognostic aspects. Patients with dual antigen positivity reported at our center and in the literature were combined and compared with PLA2R single-positive IMN reported at our center. Compared with PLA2R single-positive IMN patients, dual antigen-positive IMN patients had a higher renal tissue IgG1 positivity rate (58.3% vs. 22.3%, p=0.016), and the time required to achieve remission was longer [13.5 (3.3,35.0) vs. 3.0 (1.0,8.0), p=0.052]. Overall, The changes in urine protein were consistent with the changes in serum PLA2R antibody levels in dual antigen-positive IMN patients.
For patients with primary membranous nephropathy who did not attain remission following prolonged treatment, multiple target antigen staining should still be actively performed, even with positivity for the PLA2R target antigen.
特发性膜性肾病（IMN）是成人肾病综合征中最常见的病理类型。已经发现了许多靶抗原。然而，双抗原阳性的 IMN 患者非常罕见，只有少数此类病例在各种研究中被简要描述。目前尚无关于双抗原阳性 IMN 患者临床病理和预后特征的专门研究，此类患者的疾病特征尚不清楚。
对诊断为 IMN 的患者的肾组织样本进行 PLA2R、THSD7A 和 NELL-1 的免疫组织化学染色，同时检测相应的血清抗体。通过组织染色或血清抗体检测阳性的患者纳入研究，回顾性收集其临床、病理和随访资料，并在多个时间点测量其血清抗体水平。此外，还对本中心文献中报道的相同类型的双抗原阳性 IMN 病例进行了复习，提取临床、病理和预后信息。将本中心所有双抗原阳性和 PLA2R 单阳性 IMN 病例的数据进行比较。
本中心共发现 6 例双抗原阳性的 IMN 患者，占整个 MN 系列的 0.7%左右；文献报道的双抗原阳性 IMN 患者有 43 例，比例在 0.2%至 2.8%之间。本中心双抗原阳性患者肾组织 IgG1 阳性率明显低于文献报道的双抗原阳性患者（16.7%比 100.0%，p=0.015），但在临床或预后方面无明显差异。本中心及文献报道的双抗原阳性患者合并后与本中心 PLA2R 单阳性 IMN 患者比较，双抗原阳性 IMN 患者肾组织 IgG1 阳性率更高（58.3%比 22.3%，p=0.016），达到缓解的时间更长[13.5（3.3，35.0）比 3.0（1.0，8.0），p=0.052]。总体而言，双抗原阳性 IMN 患者的尿蛋白变化与血清 PLA2R 抗体水平的变化一致。
对于经长时间治疗未缓解的原发性膜性肾病患者，即使 PLA2R 靶抗原阳性，仍应积极进行多靶点抗原染色。
