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Circulating antibodies against M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in Chinese patients with membranous nephropathy

  • Nephrology - Original Paper
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Abstract

Background

M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) have recently been identified as target antigens for patients with idiopathic membranous nephropathy (IMN). The prevalence of PLA2R and THSD7A in the serum of MN patients deserves further investigation.

Methods

Here, we studied the presence of anti-PLA2R and anti-THSD7A antibodies in patients with biopsy-proven IMN (n = 212), secondary membranous nephropathy (SMN, n = 118), and other kidney diseases (n = 84). The progress of 49 IMN patients [anti-PLA2R(+), n = 27; anti-THSD7A(+), n = 6; anti-PLA2R(−) and anti-THSD7A(−) dual negative, n = 16] who received immunosuppressive therapy was observed for 12 months. Serum concentrations of antibodies against PLA2R and THSD7A were detected using an indirect immunofluorescent assay.

Results

One hundred fifty-two (71.7%) IMN patients and 11 (9.3%) SMN patients were identified as anti-PLA2R(+) anti-THSD7A(−). Five (2.4%) IMN patients and two (1.7%) SMN patients were identified as anti-THSD7A(+) anti-PLA2R(−). One of the IMN patients was identified as anti-PLA2R(+) and anti-THSD7A(+). The rate of partial remission was lower in anti-PLA2R(+) patients than in anti-PLA2R(−) patients 3 months (P = 0.045) and 6 months (P = 0.006) after immunosuppressive therapy. The rate of complete remission was lower in anti-PLA2R(+) patients than in anti-PLA2R(−) patients 12 months (P = 0.037) after immunosuppressive therapy.

Conclusions

The serum concentration of anti-PLA2R antibodies may be used as a sensitive and specific marker for diagnosing IMN. Immunosuppressive therapy is more effective for IMN patients who are anti-PLA2R(−) than for those who are anti-PLA2R(+).

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References

  1. Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H (2013) Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy. Nephrol Dial Transplant 28:1839–1844

    Article  CAS  PubMed  Google Scholar 

  2. Ma H, Sandor DG, Beck LH (2013) The role of complement in membranous nephropathy. Semin Nephrol 33:531–542

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rozenberg I, Kotliroff A, Zahavi T, Benchetrit S (2018) Outcome of idiopathic membranous nephropathy: a retrospective study. Isr Med Assoc J 20:186–189

    PubMed  Google Scholar 

  4. Murtas C, Ghiggeri GM (2016) Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms. J Nephrol 29:469–478

    Article  CAS  PubMed  Google Scholar 

  5. Fresquet M, Jowitt TA, Gummadova J et al (2015) Identification of a major epitope recognized by PLA2R autoantibodies in primary membranous nephropathy. J Am Soc Nephrol 26:302–313

    Article  CAS  PubMed  Google Scholar 

  6. Beck LH, Bonegio RG, Lambeau G et al (2009) M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med 361:11–21

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Radice A, Trezzi B, Maggiore U et al (2016) Clinical usefulness of autoantibodies to M-type phospholipase A2 receptor (PLA2R) for monitoring disease activity in idiopathic membranous nephropathy (IMN). Autoimmun Rev 15:146–154

    Article  CAS  PubMed  Google Scholar 

  8. Tomas NM, Beck LH, Meyer-Schwesinger C et al (2014) Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371:2277–2287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Iwakura T, Ohashi N, Kato A, Baba S, Yasuda H (2015) Prevalence of enhanced granular expression of thrombospondin type-1 domain-containing 7A in the glomeruli of Japanese patients with idiopathic membranous nephropathy. PLoS One 10:e0138841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Larsen CP, Cossey LN, Beck LH (2016) THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. Mod Pathol 29:421–426

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. L’Imperio V, Pieruzzi F, Sinico RA et al (2018) Routine immunohistochemical staining in membranous nephropathy: in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain. J Nephrol 31:543–550

    Article  CAS  PubMed  Google Scholar 

  12. Hoxha E, Harendza S, Zahner G et al (2011) An immunofluorescence test for phospholipase-A2-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant 26:2526–2532

    Article  CAS  PubMed  Google Scholar 

  13. Qin W, Beck LH, Zeng C et al (2011) Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 22:1137–1143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Akiyama S, Akiyama M, Imai E, Ozaki T, Matsuo S, Maruyama S (2015) Prevalence of anti-phospholipase A2 receptor antibodies in Japanese patients with membranous nephropathy. Clin Exp Nephrol 19:653–660

    Article  CAS  PubMed  Google Scholar 

  15. Gopalakrishnan N, Abeesh P, Dineshkumar T et al (2016) Prevalence of serum anti M-type phospholipase A2 receptor antibody in primary membranous nephropathy: a single center experience. Indian J Nephrol 26:257–261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hofstra JM, Debiec H, Short CD et al (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23:1735–1743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Dai H, Zhang H, He Y (2015) Diagnostic accuracy of PLA2R autoantibodies and glomerular staining for the differentiation of idiopathic and secondary membranous nephropathy: an updated meta-analysis. Sci Rep 5:8803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ronco P, Debiec H (2012) Pathogenesis of membranous nephropathy: recent advances and future challenges. Nat Rev Nephrol 8:203–213

    Article  CAS  PubMed  Google Scholar 

  19. Knehtl M, Debiec H, Kamgang P et al (2011) A case of phospholipase A2 receptor-positive membranous nephropathy preceding sarcoid-associated granulomatous tubulointerstitial nephritis. Am J Kidney Dis 57:140–143

    Article  PubMed  Google Scholar 

  20. Larsen CP, Messias NC, Silva FG, Messias E, Walker PD (2013) Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol 26:709–715

    Article  CAS  PubMed  Google Scholar 

  21. Ge YC, Jin B, Zeng CH et al (2016) PLA2R antibodies and PLA2R glomerular deposits in psoriasis patients with membranous nephropathy. BMC Nephrol 17:185

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sharma SG, Larsen CP (2018) Tissue staining for THSD7A in glomeruli correlates with serum antibodies in primary membranous nephropathy: a clinicopathological study. Mod Pathol 31:616–622

    Article  CAS  PubMed  Google Scholar 

  23. Wang J, Cui Z, Lu J et al (2017) Circulating antibodies against thrombospondin type-I domain-containing 7A in Chinese patients with idiopathic membranous nephropathy. Clin J Am Soc Nephrol 12:1642–1651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hayashi N, Okada K, Matsui Y et al (2018) Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy. Nephrol Dial Transplant 33:832–840

    Article  CAS  PubMed  Google Scholar 

  25. Hoxha E, Wiech T, Stahl PR et al (2016) A mechanism for cancer-associated membranous nephropathy. N Engl J Med 374:1995–1996

    Article  CAS  PubMed  Google Scholar 

  26. Li X, Wei D, Zhou Z et al (2016) Anti-PLA2R antibodies in Chinese patients with membranous nephropathy. Med Sci Monit 22:1630–1636

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was granted by the Foundation of Health and Family Planning Commission of Hubei province (Grant no. WJ2017M217).

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Authors and Affiliations

  1. Laboratory Medicine Centre, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China

    Caixia Tian & Yurong Qiu

  2. Department of Clinical Laboratory Science, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China

    Caixia Tian, Lian Li & Xin Qu

  3. Division of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China

    Tanxin Liu

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  1. Caixia Tian
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Correspondence to Yurong Qiu.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee (the Ethics Committee of Hubei University of Medicine) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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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. Int Urol Nephrol 51, 1371–1377 (2019). https://doi.org/10.1007/s11255-019-02146-w

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  • DOI: https://doi.org/10.1007/s11255-019-02146-w

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