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中华肾病研究电子杂志 ›› 2022, Vol. 11 ›› Issue (01) : 52 -56. doi: 10.3877/cma.j.issn.2095-3216.2022.01.010

综述

磷脂酶A2受体相关特发性膜性肾病研究进展
梁小雨1, 米杰2,()   
  1. 1. 250014 济南,山东中医药大学
    2. 250014 济南,山东中医药大学附属医院肾病科
  • 收稿日期:2021-08-25 出版日期:2022-02-28
  • 通信作者: 米杰
  • 基金资助:
    山东省中医药科技发展计划项目(2013ZDZK-001)

Research progress on phospholipase A2 receptor-related idiopathic membranous nephropathy

Xiaoyu Liang1, Jie Mi2,()   

  1. 1. Shandong University of Traditional Chinese Medicine
    2. Department of Nephrology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine; Jinan 250014, Shandong Province, China
  • Received:2021-08-25 Published:2022-02-28
  • Corresponding author: Jie Mi
引用本文:

梁小雨, 米杰. 磷脂酶A2受体相关特发性膜性肾病研究进展[J]. 中华肾病研究电子杂志, 2022, 11(01): 52-56.

Xiaoyu Liang, Jie Mi. Research progress on phospholipase A2 receptor-related idiopathic membranous nephropathy[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2022, 11(01): 52-56.

特发性膜性肾病(IMN)是成人肾病综合征(NS)的常见病因,近年由于不断攀升的发病率及趋于年轻化的发病年龄而受到关注。M型磷脂酶A2受体(PLA2R)抗体的发现使得IMN在诊断、治疗、评估病情及判断预后等方面取得了巨大进展。我们将血清抗PLA2R抗体(PLA2Rab)及肾小球PLA2R表达阳性的IMN定义为PLA2R相关IMN。随着PLA2Rab检测技术的发展,确诊本病的患者也越来越多,其临床表现相对于其他类型的IMN往往更为严重,治疗亦较为棘手。本文就PLA2R相关IMN的研究进展进行综述,以期为临床和科研提供参考。

Idiopathic membranous nephropathy (IMN) is a common pathogeny of nephrotic syndrome in adults. In recent years, IMN has attracted much attention due to its increasing incidence and younger age of onset. The discovery of M-type phospholipase A2 receptor (PLA2R) antibody has made great progress in diagnosis, treatment, disease assessment, and prognosis judgment of IMN. We defined the IMN with both serum anti-PLA2R antibody (PLA2Rab) and glomerular PLA2R expression as PLA2R-related IMN. With the development of detection technology for serum PLA2R antibody, more and more patients have been diagnosed. Compared with other types of IMN, the clinical manifestations of PLA2R-related IMN are often more serious while its treatment is more difficult. This paper reviewed the research progress on PLA2R-related IMN in order to provide reference for both clinical work and scientific research.

图1 膜性肾病中免疫介导的足细胞损伤机制注:Ig:免疫球蛋白;MBL: mannose-binding lectin,甘露糖结合凝集素;MASP1: MASP1: mannose-associated serine protease 1,甘露糖相关丝氨酸蛋白酶1;补体可以通过三种不同的途径激活形成C5b-9补体攻击复合物,损伤足细胞导致肾损伤;同时,抗足细胞抗体可直接改变靶抗原的功能,在没有炎症的情况下触发足细胞损伤
[1]
史玉洁,翁亚菡. 膜性肾病的病理学特点及诊断[J]. 中国临床医生杂志2019, 47(9): 1020-1023.
[2]
朱慧娴,周敏林,侯金花,等. 肾脏疾病谱的变迁:基于2003~2014年中国单中心40759例肾活检病理诊断分析[J]. 肾脏病与透析肾移植杂志2017, 26(2): 101-107.
[3]
Beck LH, Bonegio RG, Lambeau G, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy [J]. N Engl J Med, 2009, 361(1): 11-21.
[4]
van de Logt AE, Fresquet M, Wetzels JF, et al. The anti-PLA2R antibody in membranous nephropathy: what we know and what remains a decade after its discovery [J]. Kidney Int, 2019, 96(6): 1292-1302.
[5]
Liu WB, Gao C, Dai H, et al. Immunological pathogenesis of membranous nephropathy: focus on PLA2R1 and its role [J]. Front Immunol, 2019, 10: 1809.
[6]
Ancian P, Lambeau G, Mattei MG, et al. The human 180-kDa receptor for secretory phospholipases A2. Molecular cloning, identification of a secreted soluble form, expression, and chromosomal localization [J]. J Biol Chem, 1995, 270(15): 8963-8970.
[7]
Xu X, Nie S, Ding HY, et al. Environmental pollution and kidney diseases [J]. Nat Rev Nephrol, 2018, 14(5): 313-324.
[8]
潘阳彬,万建新,陶璇,等. sPLA2-ⅠB、PLA2R及PLA2R-AB在鉴别微小病变型肾病及特发性膜性肾病中的意义[J]. 华中科技大学学报(医学版), 2017, 46(6): 625-630.
[9]
Škoberne A, Behnert A, Teng B, et al. Serum with phospholipase A2 receptor autoantibodies interferes with podocyte adhesion to collagen [J]. Eur J Clin Invest, 2014, 44(8): 753-765.
[10]
Ronco P, Debiec H. Molecular pathogenesis of membranous nephropathy [J]. Annu Rev Pathol, 2020, 15: 287-313.
[11]
Meyer-Schwesinger C, Tomas NM, Dehde S, et al. A novel mouse model of phospholipase A2 receptor 1-associated membranous nephropathy mimics podocyte injury in patients [J]. Kidney Int, 2020, 97(5): 913-919.
[12]
刘兆宇,远方. 基于文献研究特发性膜性肾病的中医辨治进展[J]. 检验医学与临床2020, 17(2): 278-280,288.
[13]
Song EJ, Jeong KH, Yang YA, et al. Anti-phospholipase A2 receptor antibody as a prognostic marker in patients with primary membranous nephropathy [J]. Kidney Res Clin Pract, 2018, 37(3): 248-256.
[14]
Dong D, Fan TT, Wang YY, et al. Relationship between renal tissues phospholipase A2 receptor and its serum antibody and clinical condition and prognosis of idiopathic membranous nephropathy: a meta-analysis [J]. BMC Nephrol, 2019, 20(1): 444.
[15]
练明建,卢榕,张加勤,等. 血清抗PLA2R抗体检测对特发性膜性肾病诊断效能的meta分析[J]. 临床检验杂志2017, 35(7): 545-549.
[16]
Tian C, Li L, Liu T, et al. Circulating antibodies against M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in Chinese patients with membranous nephropathy [J]. Int Urol Nephrol, 2019, 51(8): 1371-1377.
[17]
Radice A, Pieruzzi F, Trezzi B, et al. Diagnostic specificity of autoantibodies to M-type phospholipase A2 receptor (PLA2R) in differentiating idiopathic membranous nephropathy (IMN) from secondary forms and other glomerular diseases [J]. J Nephrol, 2018, 31(2): 271-278.
[18]
蔡岩岩. PLA2R抗体在特发性膜性肾病中诊疗意义的研究进展[J]. 中国医学创新2020, 17(2): 169-172.
[19]
Dähnrich C, Saschenbrecker S, Gunnarsson I, et al. Development of a standardized chemiluminescence immunoassay for the detection of autoantibodies against human m-type phospholipase A2 receptor in primary membranous nephropathy [J]. Kidney Int Rep, 2020, 5(2): 182-188.
[20]
Bobart SA, De Vriese AS, Pawar AS, et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies [J]. Kidney Int, 2019, 95(2): 429-438.
[21]
Hofstra JM, Beck LH, Beck DM, et al. Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy [J]. Clin J Am Soc Nephrol, 2011, 6(6): 1286-1291.
[22]
Wu W, Shang J, Tao C, et al. The prognostic value of phospholipase A2 receptor autoantibodies on spontaneous remission for patients with idiopathic membranous nephropathy: a meta-analysis [J]. Medicine (Baltimore), 2018, 97(23): e11018.
[23]
Guerry MJ, Vanhille P, Ronco P, et al. Serum anti-PLA2R antibodies may be present before clinical manifestations of membranous nephropathy [J]. Kidney Int, 2016, 89(6): 1399.
[24]
De Vriese AS, Glassock RJ, Nath KA, et al. A proposal for a serology-based approach to membranous nephropathy [J]. J Am Soc Nephrol, 2017, 28(2): 421-430.
[25]
Jha V, Ganguli A, Saha TK, et al. A randomized, controlled trial of steroids and cyclophosphamide in adults with nephrotic syndrome caused by idiopathic membranous nephropathy [J]. J Am Soc Nephrol, 2007, 18(6): 1899-1904.
[26]
van de Logt AE, Dahan K, Rousseau A, et al. Immunological remission in PLA2R-antibody-associated membranous nephropathy: cyclophosphamide versus rituximab [J]. Kidney Int, 2018, 93(4): 1016-1017.
[27]
Xie Z, Dong W, Li Z, et al. Clinical value of renal phospholipase A2 receptor deposit in the prognosis evaluation and treatment options of idiopathic membranous nephropathy: A retrospective cohort study [J]. Nephrology (Carlton), 2020, 25(3): 219-229.
[28]
徐平,何雨荻,于泽铭,等. 环孢素A和他克莫司治疗特发性膜性肾病的有效性及安全性比较:网状Meta分析[J]. 中国医学科学院学报2018, 40(1): 41-51.
[29]
姚杏,聂丽敏,张珊珊,等. 环孢素联合小剂量糖皮质激素对PLA2R阳性膜性肾病患者疗效及T淋巴细胞亚群的影响观察[J]. 中国药师2020, 23(5): 891-894.
[30]
黄俊,李剑文,梁鸣,等. 他克莫司联合激素治疗血清抗PLA2R抗体持续高滴度的难治性特发性膜性肾病[J]. 实用医学杂志2018, 34(8): 1355-1359.
[31]
Chen S, Ren S, Wang AY, et al. Comparison of the efficacy and safety of tacrolimus monotherapy and cyclophosphamide combined with glucocorticoid in the treatment of adult primary membranous nephropathy: protocol of a multicenter, randomized, controlled, open study [J]. Trials, 2020, 21(1): 219.
[32]
Ronco P, Plaisier E, Debiec H. Advances in membranous nephropathy [J]. J Clin Med, 2021, 10(4): 607.
[33]
Guo Y, Wu X, Liu L, et al. Efficacy of leflunomide combined with prednisone for the treatment of PLA2R-associated primary membranous nephropathy [J]. Ren Fail, 2020, 42(1): 122-130.
[34]
Zheng Q, Yang H, Liu W, et al. Comparative efficacy of 13 immunosuppressive agents for idiopathic membranous nephropathy in adults with nephrotic syndrome: a systematic review and network meta-analysis [J]. BMJ Open, 2019, 9(9): e030919.
[35]
Nikolopoulou A, Condon M, Turner-Stokes T, et al. Mycophenolate mofetil and tacrolimus versus tacrolimus alone for the treatment of idiopathic membranous glomerulonephritis: a randomised controlled trial [J]. BMC Nephrol, 2019, 20(1): 352.
[36]
黄俊,李剑文,梁鸣,等. 霉酚酸酯联合激素治疗血清抗PLA2R抗体阳性特发性膜性肾病[J]. 中国综合临床2017, 33(7): 577-582.
[37]
Fervenza FC, Appel GB, Barbour SJ, et al. Rituximab or cyclosporine in the treatment of membranous nephropathy [J]. N Engl J Med, 2019, 381(1): 36-46.
[38]
Fernández-Juárez G, Rojas-Rivera J, Logt AV, et al. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy [J]. Kidney Int, 2021, 99(4): 986-998.
[39]
Hanset N, Esteve E, Plaisier E, et al. Rituximab in patients with phospholipase A2 receptor-associated membranous nephropathy and severe CKD [J]. Kidney Int Rep, 2019, 5(3): 331-338.
[40]
Klomjit N, Fervenza FC, Zand L. Successful treatment of patients with refractory PLA2R-associated membranous nephropathy with obinutuzumab: a report of 3 cases [J]. Am J Kidney Dis, 2020, 76(6): 883-888.
[41]
Sethi S, Kumar S, Lim K, et al. Obinutuzumab is effective for the treatment of refractory membranous nephropathy [J]. Kidney Int Rep, 2020, 5(9): 1515-1518.
[42]
Xu Z, Chen L, Xiang H, et al. Advances in pathogenesis of idiopathic membranous nephropathy [J]. Kidney Dis (Basel), 2020, 6(5): 330-345.
[43]
鲁盈,严小倩. 雷公藤的毒副作用及在肾病中的合理应用[J/CD]. 中华肾病研究电子杂志2018, 7(1): 17-22.
[44]
丁琪. 雷公藤联合低剂量环孢素治疗PLA2R相关性膜性肾病患者临床研究[J]. 实用中西医结合临床2021, 21(3): 64-66.
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