The Prevalence, Characteristics, and Putative Mechanisms of Dual Antigen-Positive Membranous Nephropathy: The Underestimated Condition

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jun 19

PMID 38892120

Authors

Takahiro Uchida

Takashi Oda

Affiliations

Soon will be listed here.

Abstract

Following the discovery of podocyte phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A, various potential target antigens for membranous nephropathy (MN) have been reported one after another. MN target antigens have now been identified in a significant proportion of patients, and a new classification framework classifies patients with MN based on the detected antigen and associated disease phenotype. A serology-based approach that does not require a histological diagnosis for patients suspected of having MN has also been proposed. However, there have been cases in which dual positivity for MN antigens and/or corresponding antibodies has been shown. Importantly, some of them showed a transition of the affected patient's immune responses to MN antigens, suggesting that serological diagnosis changes depending on the timing of the analysis. In this review, we provide detailed information on these cases and present an overview of our recent understanding of their putative mechanisms involved in these cases. Greater awareness is required to adequately recognize and develop appropriate therapeutic strategies for this condition.

References

Sethi S, Madden B, Debiec H, Morelle J, Charlesworth M, Gross L . Protocadherin 7-Associated Membranous Nephropathy. J Am Soc Nephrol. 2021; 32(5):1249-1261. PMC: 8259689. DOI: 10.1681/ASN.2020081165. View

Wang G, Sun L, Dong H, Wang Y, Xu X, Zhao Z . Neural Epidermal Growth Factor-Like 1 Protein-Positive Membranous Nephropathy in Chinese Patients. Clin J Am Soc Nephrol. 2021; 16(5):727-735. PMC: 8259482. DOI: 10.2215/CJN.11860720. View

Fresquet M, Rhoden S, Jowitt T, McKenzie E, Roberts I, Lennon R . Autoantigens PLA2R and THSD7A in membranous nephropathy share a common epitope motif in the N-terminal domain. J Autoimmun. 2019; 106:102308. PMC: 7471840. DOI: 10.1016/j.jaut.2019.102308. View

Sethi S, Debiec H, Madden B, Vivarelli M, Charlesworth M, Ravindran A . Semaphorin 3B-associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients. Kidney Int. 2020; 98(5):1253-1264. DOI: 10.1016/j.kint.2020.05.030. View

Fervenza F, Appel G, Barbour S, Rovin B, Lafayette R, Aslam N . Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy. N Engl J Med. 2019; 381(1):36-46. DOI: 10.1056/NEJMoa1814427. View

Du Y, Li J, He F, Lv Y, Liu W, Wu P . The diagnosis accuracy of PLA2R-AB in the diagnosis of idiopathic membranous nephropathy: a meta-analysis. PLoS One. 2014; 9(8):e104936. PMC: 4138154. DOI: 10.1371/journal.pone.0104936. View

Xie Q, Li Y, Xue J, Xiong Z, Wang L, Sun Z . Renal phospholipase A2 receptor in hepatitis B virus-associated membranous nephropathy. Am J Nephrol. 2015; 41(4-5):345-53. DOI: 10.1159/000431331. View

De Vriese A, Glassock R, Nath K, Sethi S, Fervenza F . A Proposal for a Serology-Based Approach to Membranous Nephropathy. J Am Soc Nephrol. 2016; 28(2):421-430. PMC: 5280030. DOI: 10.1681/ASN.2016070776. View

Wada T, Ishimoto T, Nakaya I, Kawaguchi T, Sofue T, Shimizu S . A digest of the Evidence-Based Clinical Practice Guideline for Nephrotic Syndrome 2020. Clin Exp Nephrol. 2021; 25(12):1277-1285. DOI: 10.1007/s10157-021-02098-5. View

10.

Tomas N, Beck Jr L, Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G . Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014; 371(24):2277-2287. PMC: 4278759. DOI: 10.1056/NEJMoa1409354. View

11.

Miller P, Lei L, Charu V, Higgins J, Troxell M, Kambham N . Clinicopathologic features of non-lupus membranous nephropathy in a pediatric population. Pediatr Nephrol. 2022; 37(12):3127-3137. DOI: 10.1007/s00467-022-05503-7. View

12.

Beck Jr L, Bonegio R, Lambeau G, Beck D, Powell D, Cummins T . M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009; 361(1):11-21. PMC: 2762083. DOI: 10.1056/NEJMoa0810457. View

13.

Nasr S, Said S, Valeri A, Stokes M, Masani N, DAgati V . Membranous glomerulonephritis with ANCA-associated necrotizing and crescentic glomerulonephritis. Clin J Am Soc Nephrol. 2009; 4(2):299-308. PMC: 2637583. DOI: 10.2215/CJN.04060808. View

14.

Hoxha E, Reinhard L, Stahl R . Membranous nephropathy: new pathogenic mechanisms and their clinical implications. Nat Rev Nephrol. 2022; 18(7):466-478. DOI: 10.1038/s41581-022-00564-1. View

15.

Subramanian P, Kumar H, Tiwari B, Barwad A, Bagchi S, Bagga A . Profile of Indian Patients With Membranous Nephropathy. Kidney Int Rep. 2020; 5(9):1551-1557. PMC: 7486174. DOI: 10.1016/j.ekir.2020.06.024. View

16.

Ghiggeri G, Seitz-Polski B, Justino J, Zaghrini C, Payre C, Brglez V . Multi-Autoantibody Signature and Clinical Outcome in Membranous Nephropathy. Clin J Am Soc Nephrol. 2020; 15(12):1762-1776. PMC: 7769033. DOI: 10.2215/CJN.02500220. View

17.

Iwakura T, Ema C, Isobe S, Fujikura T, Ohashi N, Kato A . Prevalence of neural epidermal growth factor-like 1- and exostosin 1/exostosin 2-associated membranous nephropathy: a single-center retrospective study in Japan. Sci Rep. 2022; 12(1):2967. PMC: 8864000. DOI: 10.1038/s41598-022-07037-2. View

18.

le Quintrec M, Teisseyre M, Bec N, Delmont E, Szwarc I, Perrochia H . Contactin-1 is a novel target antigen in membranous nephropathy associated with chronic inflammatory demyelinating polyneuropathy. Kidney Int. 2021; 100(6):1240-1249. DOI: 10.1016/j.kint.2021.08.014. View

19.

Troyanov S, Roasio L, Pandes M, Herzenberg A, Cattran D . Renal pathology in idiopathic membranous nephropathy: a new perspective. Kidney Int. 2006; 69(9):1641-8. DOI: 10.1038/sj.ki.5000289. View

20.

Couser W . Primary Membranous Nephropathy. Clin J Am Soc Nephrol. 2017; 12(6):983-997. PMC: 5460716. DOI: 10.2215/CJN.11761116. View