Target Antigens of Membranous Nephropathy With Syphilis Infection

Overview

Journal Kidney Int Rep

Publisher Elsevier

Specialty Nephrology

Date 2024 Feb 12

PMID 38344711

Authors

Liyin Zhang

Minfang Zhang

Qionghong Xie

Yongxiang Wang

Zhaohui Ni

Shaojun Liu

Wenyan Zhou

Affiliations

Soon will be listed here.

Abstract

Introduction: Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown.

Methods: A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed.

Results: Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection.

Conclusion: Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.

References

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

Caza T, Hassen S, Kuperman M, Sharma S, Dvanajscak Z, Arthur J . Neural cell adhesion molecule 1 is a novel autoantigen in membranous lupus nephritis. Kidney Int. 2020; 100(1):171-181. PMC: 8032825. DOI: 10.1016/j.kint.2020.09.016. View

Wanderley D, de Menezes Neves P, Jorge L, Onuchic L, Araujo S . The immunohistological profile of membranous nephropathy associated with syphilis infection. Clin Kidney J. 2021; 14(7):1857-1858. PMC: 8243262. DOI: 10.1093/ckj/sfab057. View

Yasuda I, Tokuyama H, Hashiguchi A, Hasegawa K, Uchiyama K, Ryuzaki M . Malignancy-associated membranous nephropathy with PLA2R double-positive for glomeruli and carcinoma. CEN Case Rep. 2021; 10(2):281-286. PMC: 8019443. DOI: 10.1007/s13730-020-00556-9. View

Kuang X, Zhao X, Xu H, Shi Y, Deng J, Sun G . Spatio-temporal expression of a novel neuron-derived neurotrophic factor (NDNF) in mouse brains during development. BMC Neurosci. 2010; 11:137. PMC: 2984559. DOI: 10.1186/1471-2202-11-137. View

Caza T, Hassen S, Dvanajscak Z, Kuperman M, Edmondson R, Herzog C . NELL1 is a target antigen in malignancy-associated membranous nephropathy. Kidney Int. 2020; 99(4):967-976. PMC: 7895854. DOI: 10.1016/j.kint.2020.07.039. View

Shettigar R, Schollum J, Putt T, Chan L, Lau M, Walker R . Renal manifestations of syphilis. Intern Med J. 2021; 51(7):1160-1167. DOI: 10.1111/imj.15407. View

Ravindran A, Casal Moura M, Fervenza F, Nasr S, Alexander M, Fidler M . In Patients with Membranous Lupus Nephritis, Exostosin-Positivity and Exostosin-Negativity Represent Two Different Phenotypes. J Am Soc Nephrol. 2021; 32(3):695-706. PMC: 7920177. DOI: 10.1681/ASN.2020081181. View

Sethi S, Madden B, Casal Moura M, Singh R, Nasr S, Hou J . Membranous Nephropathy in Syphilis is Associated with Neuron-Derived Neurotrophic Factor. J Am Soc Nephrol. 2023; 34(3):374-384. PMC: 10103242. DOI: 10.1681/ASN.0000000000000061. View

10.

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

11.

Sethi S, Madden B . Mapping antigens of membranous nephropathy: almost there. Kidney Int. 2023; 103(3):469-472. DOI: 10.1016/j.kint.2023.01.003. View

12.

Al-Rabadi L, Beck Jr L . Neuronal Proteins as Antigenic Targets in Membranous Nephropathy. Nephron. 2022; 147(8):451-457. DOI: 10.1159/000528078. View

13.

Hazue R, Ueno T, Nozaki H, Kinowaki K, Ohashi K, Hoshino J . Syphilis-associated membranous nephropathy successfully treated with amoxicillin. Clin Nephrol. 2021; 96(5):297-301. DOI: 10.5414/CN110586. View

14.

Sethi S, Madden B, Casal Moura M, Nasr S, Klomjit N, Gross L . Hematopoietic Stem Cell Transplant-Membranous Nephropathy Is Associated with Protocadherin FAT1. J Am Soc Nephrol. 2022; 33(5):1033-1044. PMC: 9063902. DOI: 10.1681/ASN.2021111488. View

15.

Reinhard L, Machalitza M, Wiech T, Grone H, Lasse M, Rinschen M . Netrin G1 Is a Novel Target Antigen in Primary Membranous Nephropathy. J Am Soc Nephrol. 2022; 33(10):1823-1831. PMC: 9528326. DOI: 10.1681/ASN.2022050608. View

16.

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

17.

Garcia-Vives E, Sole C, Moline T, Alvarez-Rios A, Vidal M, Agraz I . Antibodies to M-type phospholipase A2 receptor (PLAR) in membranous lupus nephritis. Lupus. 2019; 28(3):396-405. DOI: 10.1177/0961203319828521. View

18.

Gamble C, REARDAN J . Immunopathogenesis of syphilitic glomerulonephritis. Elution of antitreponemal antibody from glomerular immune-complex deposits. N Engl J Med. 1975; 292(9):449-54. DOI: 10.1056/NEJM197502272920903. View

19.

Hoxha E, Wiech T, Stahl P, Zahner G, Tomas N, Meyer-Schwesinger C . A Mechanism for Cancer-Associated Membranous Nephropathy. N Engl J Med. 2016; 374(20):1995-6. DOI: 10.1056/NEJMc1511702. View

20.

Sethi S, Debiec H, Madden B, Charlesworth M, Morelle J, Gross L . Neural epidermal growth factor-like 1 protein (NELL-1) associated membranous nephropathy. Kidney Int. 2020; 97(1):163-174. DOI: 10.1016/j.kint.2019.09.014. View