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中华肾病研究电子杂志

中华肾病研究电子杂志 ›› 2026, Vol. 15 ›› Issue (01) : 39 -45. doi: 10.3877/cma.j.issn.2095-3216.2026.01.007

综述

膜性肾病相关抗原及其靶向治疗的研究进展
虎成, 王晨丹†()   
  1. 030012　山西医科大学附属省人民医院肾内科
  • 收稿日期:2025-01-20 出版日期:2026-02-28
  • 通信作者: 王晨丹
  • 基金资助:
    山西省自然科学研究面上项目(202103021224382)

Research advances in membranous nephropathy: associated antigens and targeted therapy

Cheng Hu, Chendan Wang†()   

  1. Department of Nephrology, Shanxi Provincial People′s Hospital Affiliated to Shanxi Medical University, Taiyuan 030012, Shanxi Province, China
  • Received:2025-01-20 Published:2026-02-28
  • Corresponding author: Chendan Wang
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引用本文：

虎成, 王晨丹. 膜性肾病相关抗原及其靶向治疗的研究进展[J/OL]. 中华肾病研究电子杂志, 2026, 15(01): 39-45.

Cheng Hu, Chendan Wang. Research advances in membranous nephropathy: associated antigens and targeted therapy[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2026, 15(01): 39-45.

膜性肾病(membranous nephropathy，MN)是以肾小球基底膜弥漫增厚伴上皮细胞下免疫复合物沉积为特征的肾小球疾病，传统诊断依赖肾活检病理。近年来，一些靶抗原的发现革新了MN的诊疗模式，基于抗原分类的精准分型显著提升了诊断特异性与预后评估能力。研究证实，不同抗原的临床异质性显著：M型磷脂酶A2受体(M-type phospholipase A2 receptor，PLA2R)和血小板反应蛋白1型结构域蛋白7A(thrombospondin type-1 domain-containing 7A，THSD7A)可能与恶性肿瘤风险相关；神经表皮生长因子样1(neural epidermal growth factor-like 1，NELL1)关联多因素致病特征；外生骨疣素1/2(exostosin 1/2，EXT1/2)则提示狼疮性肾炎亚型；而信号素3B(semaphorin 3B，SEMA3B)、神经源性神经营养因子(neuron-derived neurotrophic factor，NDNF)等抗原分别指向儿童MN及梅毒相关性MN。治疗方面，传统免疫抑制方案(如利妥昔单抗)仍是核心，但新型靶向疗法(清扫抗体技术、嵌合抗原受体T细胞疗法及免疫吸附)通过精准清除致病抗体或B细胞展现出潜力，其疗效与安全性仍需长期验证。本文系统梳理了MN的抗原谱临床意义及治疗进展，为个体化诊疗提供参考。

关键词: 膜性肾病, 足细胞抗原, 肾病综合征, 自身免疫, 靶向治疗

Membranous nephropathy (MN) is a glomerular disease characterized by diffuse thickening of the glomerular basement membrane and subepithelial immune complex deposition. Traditionally MN is diagnosed via renal biopsy pathology. In recent years, the discovery of some target antigens has revolutionized the diagnosis and treatment of MN. Precise typing based on antigen classification has significantly improved diagnostic specificity and prognostic assessment capabilities. Research has confirmed that clinical heterogeneity of different antigens is significant: M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) may be associated with the risk of malignancy; neural epidermal growth factor-like 1 (NELL1) is associated with multifactorial pathogenic characteristics; exostosin glycosyltransferase 1/2 (EXT1/2) indicates subtypes of lupus nephritis; while semaphorin 3B (SEMA3B) and neuron-derived neurotrophic factor (NDNF) point to childhood MN and syphilis-related MN, respectively. In terms of treatment, traditional immunosuppressive regimens (such as rituximab) remain the core therapy, but novel targeted therapies (including antibody clearance technology, chimeric antigen receptor T-cell therapy, and immunoadsorption) have shown potential by precisely eliminating pathogenic antibodies or B cells, although their efficacy and safety still require long-term verification. This article systematically reviewed the clinical significance of the antigens spectrum and therapeutic advancements of MN, providing a reference for individualized diagnosis and treatment.

Key words: Membranous nephropathy, Podocyte antigen, Nephrotic syndrome, Autoimmune, Targeted therapy
表1 膜性肾病相关抗原特点
抗原名称 临床关联 发病率 病理特征 检测到循环自身抗体
PLA2R 原发性膜性肾病，目前有相关报道提示与肿瘤相关 70%~80%的"原发性"膜性肾病病例 弥漫性上皮下免疫沉积，IgG4(共)显性 是
THSD7A 恶性肿瘤(11%~20%)，部分为"原发性" 2%~5%的膜性肾病；8%~14%的PLA2R阴性病例 上皮下免疫沉积 是
NELL1 恶性肿瘤(0~33%)、硫辛酸使用、含汞传统药物、移植物抗宿主病、结节病、感染 4%~6%的膜性肾病；6%~21%的PLA2R阴性病例 节段性上皮下免疫沉积，IgG1显性 是
PCDH 7 部分患者有自身免疫性疾病(如干燥综合征、结节病)或肿瘤 5.7%的PLA2R阴性病例 上皮下沉积，偶见管状网状包涵体 是
HTRA1 无明显关联 3.3%的PLA2R阴性病例 弥漫性上皮下免疫沉积，IgG4显性 是
EXT1/2 系统性红斑狼疮或其他自身免疫性疾病 17%~33%的狼疮性膜性肾病 合并增生性狼疮性肾炎(25%) 尚未报道
NCAM1 主要见于系统性红斑狼疮，可能与神经精神症状相关 7%的狼疮性膜性肾病；2%的"原发性"膜性肾病 合并增生性狼疮性肾炎(25%) 是
TGFBR3 主要见于系统性红斑狼疮 6%的狼疮性膜性肾病 合并增生性狼疮性肾炎(30%) 尚未报道
信号素3B 儿童(尤其≤2岁) 1%的膜性肾病；5%~10%的儿童膜性肾病 弥漫性上皮下沉积，IgG1显性，偶见肾小管基底膜沉积 是
NTNG1 无明显关联 0.2%的膜性肾病；0.4%的PLA2R/THSD7A阴性病例 上皮下免疫沉积，IgG4(共)显性 是
CNTN1 慢性炎症性脱髓鞘性多发性神经病(CIDP) 罕见 上皮下免疫沉积，IgG4显性，抗体可结合神经髓鞘组织 是(可同时结合神经组织)
FAT1 造血干细胞移植后移植物抗宿主病 仅见于HSCT患者 上皮下及肾小管基底膜免疫沉积，IgG4(共)显性 是
NDNF 梅毒 8例报道病例中6例与梅毒相关 早期上皮下免疫沉积，IgG1显性 是
PCSK6 非甾体抗炎药使用相关 极低(仅见于NSAID相关病例) 上皮下免疫沉积(具体IgG亚型未明确) 是
表2 不同治疗方法特点
治疗方法 优点 缺点 适用人群 未来研究方向
清扫抗体技术 1.高特异性(靶向PLA2R/THSD7A)
2.循环清除机制，降低治疗频率		 1.疗效持续性有限
2.长期安全性未知		 1.传统治疗无效者
2.免疫抑制高风险患者		 1.优化抗体半衰期
2.真实世界长期安全性研究
CAR-T细胞疗法 1.精准清除致病B细胞
2.潜在治愈性(单次治疗可能长期缓解)		 1.细胞因子释放综合征风险高
2.技术复杂，脱靶风险		 1.传统治疗无效者
2.免疫抑制高风险患者		 开发非病毒转导系统降低毒性
免疫吸附疗法 1.快速清除抗体(如PLA2R)
2．无免疫抑制，感染风险低		 疗效短暂(60%复发) 1.高抗体滴度伴急性肾损伤者
2.免疫抑制禁忌者(如感染，肿瘤)		 1.开发抗原特异性吸附柱(如PLA2R靶向)
2.联合利妥昔单抗延长缓解期
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