Clinical significance of the determination of antibodies to thrombospondin type 1 containing domain 7A (THSD7A) in membranous nephropathy

封面

如何引用文章

全文:

详细

Background. Membranous nephropathy (MN) is an immunocomplex glomerular disease, which is the most common cause of nephrotic syndrome in adults. Numerous studies have established that autoantibodies against the target podocyte autoantigens, including the thrombospondin type 1 domain containing 7A (THSD7A), play a leading role in the development of idiopathic MN.

Aim. To evaluate the prevalence of anti-THSD7A autoantibodies (anti-THSD7A AB) in a group of Russian patients with MN.

Materials and methods. Serum titers of anti-THSD7A AB were tested in 61 patients with biopsy-proven MN and 12 healthy controls.

Results. The prevalence of anti-THSD7A AB was not differing significantly in patients with MN and in the control group (110.9 [71.63; 210.62] and 159.25 [125.64; 231.97] pg/ml, respectively; p=0.111). When comparing subgroups of anti-PLA2R-negative patients and patients who did not receive immunosuppressive therapy with the control group, there were also no statistically significant differences in the Anti-THSD7A AB levels (p>0.05). In the MN group, 1 (1.6%) patient was anti-THSD7A-positive: a 60-year-old man with anti-PLA2R-negative MN and the presence of hormonally inactive adenomas of both adrenal glands and colon polyps (villous adenoma with focal moderate dysplasia, tubulo-villous and tubular adenoma with focal moderate severe dysplasia).

Conclusion. THSD7-associated MN is a rare variant of MN and is usually detected in PLA2R-negative patients. Screening for malignancies in THSD7A-positive MN patients is proposed.

作者简介

Patimat Kakhsurueva

Sechenov First Moscow State Medical University (Sechenov University)

Email: kamyshova_e_s@staff.sechenov.ru
ORCID iD: 0009-0002-6138-870X

аспирант каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского

俄罗斯联邦, Moscow

Elena Kamyshova

Sechenov First Moscow State Medical University (Sechenov University)

编辑信件的主要联系方式.
Email: kamyshova_e_s@staff.sechenov.ru
ORCID iD: 0000-0002-1823-0125

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского

俄罗斯联邦, Moscow

Irina Bobkova

Sechenov First Moscow State Medical University (Sechenov University)

Email: kamyshova_e_s@staff.sechenov.ru
ORCID iD: 0000-0002-8007-5680

д-р мед. наук, проф. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского

俄罗斯联邦, Moscow

Ekaterina Stavrovskaya

Sechenov First Moscow State Medical University (Sechenov University)

Email: kamyshova_e_s@staff.sechenov.ru
ORCID iD: 0000-0001-6381-2186

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского

俄罗斯联邦, Moscow

Tatiana Rudenko

Sechenov First Moscow State Medical University (Sechenov University)

Email: kamyshova_e_s@staff.sechenov.ru
ORCID iD: 0000-0002-1296-4494

канд. мед. наук, доц. каф. внутренних, профессиональных болезней и ревматологии Института клинической медицины им. Н.В. Склифосовского

俄罗斯联邦, Moscow

Elena Andreeva

Sechenov First Moscow State Medical University (Sechenov University)

Email: kamyshova_e_s@staff.sechenov.ru

канд. мед. наук, врач-нефролог клиники ревматологии, нефрологии и профпатологии им. Е.М. Тареева Университетской клинической больницы №3

俄罗斯联邦, Moscow

参考

  1. Debiec H, Guigonis V, Mougenot B, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med. 2002;346(26):2053-60. doi: 10.1056/NEJMoa012895
  2. Madaio MP, Salant DJ, Cohen AJ, et al. Comparative study of in situ immune deposit formation in active and passive Heymann nephritis. Kidney Int. 1983;23(3):498-505. doi: 10.1038/ki.1983.47
  3. Beck LH Jr., Bonegio RG, Lambeau G, et al. M-Type Phospholipase A2 Receptor as Target Antigen in IdiopathicMembranous Nephropathy. N Engl J Med. 2009;361(1):11-21. doi: 10.1056/NEJMoa0810457
  4. Qin W, Beck LH Jr., Zeng C, et al. Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol. 2011;22(6):1137-43. doi: 10.1681/ASN.2010090967
  5. Hoxha E, Harendza S, Zahner G, et al. An immunofluorescence test for phospholipase-A₂-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant. 2011;26(8):2526-32. doi: 10.1093/ndt/gfr247
  6. Akiyama S, Akiyama M, Imai E, et al. Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy. Clin Exp Nephrol. 2015;19(4):653-60. doi: 10.1007/s10157-014-1054-2
  7. Hayashi N, Akiyama S, Okuyama H, et al. Clinicopathological characteristics of M-type phospholipase A2 receptor (PLA2R)-related membranous nephropathy in Japanese. Clin Exp Nephrol. 2015;19(5):797-803. doi: 10.1007/s10157-014-1064-0
  8. Hara S, Goto S, Kamiura N, et al. Reappraisal of PLA2R1 in membranous nephropathy: immunostaining method influence and association with IgG4-dominant phenotype. Virchows Arch. 2015;467(1):87-94. doi: 10.1007/s00428-015-1754-3
  9. Bobart SA, De Vriese AS, Pawar AS, et al. Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies. Kidney Int. 2019;95:429-38. doi: 10.1016/j.kint.2018.10.021
  10. De Vriese AS, Glassock RJ, Nath KA, et al. A proposal for a serology-based approach to membranous nephropathy. J Am Soc Nephrol. 2017;28:421-30. doi: 10.1681/ASN.2016070776
  11. Hofstra JM, Beck LH Jr., Beck DM, et al. Anti-Phospholipase A(2) Receptor Antibodies Correlate With Clinical Status in Idiopathic Membranous Nephropathy. Clin J Am Soc Nephrol. 2011;6(6):1286-91. doi: 10.2215/CJN.07210810
  12. Bech AP, Hofstra JM, Brenchley PE, Wetzels JF. Association of anti-PLA₂R antibodies with outcomes after immunosuppressive therapy in idiopathic membranous nephropathy. Clin J Am Soc Nephrol. 2014;9(8):1386-92. doi: 10.2215/CJN.10471013
  13. Ruggenenti P, Debiec H, Ruggiero B, et al. Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy. J Am Soc Nephrol. 2015;26(10):2545-58. doi: 10.1681/ASN.2014070640
  14. Kanigicherla D, Gummadova J, McKenzie EA, et al. Anti-PLA2R Antibodies Measured by ELISA Predict Long-Term Outcome in a Prevalent Population of Patients With Idiopathic Membranous Nephropathy. Kidney Int. 2013;83(5):940-8. doi: 10.1038/ki.2012.486
  15. Quintana LF, Blasco M, Seras M, et al. Antiphospholipase A2 Receptor Antibody Levels Predict the Risk of Posttransplantation Recurrence of Membranous Nephropathy. Transplantation. 2015;99(8):1709-14. doi: 10.1097/TP.0000000000000630
  16. Tomas NM, Beck LH Jr., Meyer-Schwesinger C, et al. Thrombospondin Type-1 Domain-Containing 7A in Idiopathic Membranous Nephropathy. N Engl J Med. 2014;371(24):2277-87. doi: 10.1056/NEJMoa1409354
  17. Hoxha E, Beck LH Jr., Wiech T, et al. An Indirect Immunofluorescence Method Facilitates Detection of Thrombospondin Type 1 Domain-Containing 7A-Specific Antibodies in Membranous Nephropathy. J Am Soc Nephrol. 2017;28(2):520-31. doi: 10.1681/ASN.2016010050
  18. Wang J, Cui Z, Lu J, et al. Circulating Antibodies against Thrombospondin Type-I Domain-Containing 7A in Chinese Patients with Idiopathic Membranous Nephropathy. Clin J Am Soc Nephrol. 2017;12(10):1642-51. doi: 10.2215/CJN.01460217
  19. Tomas NM, Hoxha E, Reinicke AT, et al. Autoantibodies against thrombospondin type 1 domain-containing 7A induce membranous nephropathy. J Clin Invest. 2016;126(7):2519-32. doi: 10.1172/JCI85265
  20. Tomas NM, Meyer-Schwesinger C, von Spiegel H, et al. A Heterologous Model of Thrombospondin Type 1 Domain-Containing 7A-Associated Membranous Nephropathy. J Am Soc Nephrol. 2017;28(11):3262-77. doi: 10.1681/ASN.2017010030
  21. Hoxha E, Wiech T, Stahl PR, et al. A Mechanism for Cancer-Associated Membranous Nephropathy. N Engl J Med. 2016;374(20):1995-6. doi: 10.1056/NEJMc1511702
  22. Liu Y, Zheng S, Ma C, et al. Meta-Analysis of the Diagnostic Efficiency of THSD7A-AB for the Diagnosis of Idiopathic Membranous Nephropathy. Glob Chall. 2020;4(11):1900099. doi: 10.1002/gch2.201900099
  23. Zaghrini C, Seitz-Polski B, Justino J, et al. Novel ELISA for thrombospondin type 1 domain-containing 7A autoantibodies in membranous nephropathy. Kidney Int. 2019;95(3):666-79. doi: 10.1016/j.kint.2018.10.024
  24. Sharma SG, Larsen CP. Tissue staining for THSD7A in glomeruli correlates with serum antibodies in primary membranous nephropathy: a clinicopathological study. Mod Pathol. 2018;31(4):616-22. doi: 10.1038/modpathol.2017.163
  25. Hara S, Tsuji T, Fukasawa Y, et al. Clinicopathological characteristics of thrombospondin type 1 domain-containing 7A-associated membranous nephropathy. Virchows Arch. 2019;474(6):735-43. doi: 10.1007/s00428-019-02558-0
  26. Ren S, Wu C, Zhang Y, et al. An update on clinical significance of use of THSD7A in diagnosing idiopathic membranous nephropathy: a systematic review and meta-analysis of THSD7A in IMN. Ren Fail. 2018;40(1):306-13. doi: 10.1080/0886022X.2018.1456457
  27. Leeaphorn N, Kue-A-Pai P, Thamcharoen N, et al. Prevalence of cancer in membranous nephropathy: a systematic review and meta-analysis of observational studies. Am J Nephrol. 2014;40(1):29-35. doi: 10.1159/000364782

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. Antibody levels to THSD7A in general and control groups.

下载 (61KB)
索引源数据

版权所有 © Consilium Medicum, 2023

Creative Commons License
此作品已接受知识共享署名-非商业性使用-相同方式共享 4.0国际许可协议的许可。
 
 


##common.cookie##