Skip to main content
Top
Published in: International Urology and Nephrology 8/2019

01-08-2019 | Nephrology - Original Paper

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

Authors: Caixia Tian, Lian Li, Tanxin Liu, Xin Qu, Yurong Qiu

Published in: International Urology and Nephrology | Issue 8/2019

Login to get access

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(+).
Literature
1.
go back to reference 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 28:1839–1844CrossRefPubMed 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 28:1839–1844CrossRefPubMed
3.
go back to reference Rozenberg I, Kotliroff A, Zahavi T, Benchetrit S (2018) Outcome of idiopathic membranous nephropathy: a retrospective study. Isr Med Assoc J 20:186–189PubMed Rozenberg I, Kotliroff A, Zahavi T, Benchetrit S (2018) Outcome of idiopathic membranous nephropathy: a retrospective study. Isr Med Assoc J 20:186–189PubMed
4.
go back to reference Murtas C, Ghiggeri GM (2016) Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms. J Nephrol 29:469–478CrossRefPubMed Murtas C, Ghiggeri GM (2016) Membranous glomerulonephritis: histological and serological features to differentiate cancer-related and non-related forms. J Nephrol 29:469–478CrossRefPubMed
5.
go back to reference 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 26:302–313CrossRefPubMed 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 26:302–313CrossRefPubMed
6.
go back to reference 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 361:11–21CrossRefPubMedPubMedCentral 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 361:11–21CrossRefPubMedPubMedCentral
7.
go back to reference 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 15:146–154CrossRefPubMed 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 15:146–154CrossRefPubMed
8.
go back to reference Tomas NM, Beck LH, Meyer-Schwesinger C et al (2014) Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371:2277–2287CrossRefPubMedPubMedCentral Tomas NM, Beck LH, Meyer-Schwesinger C et al (2014) Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med 371:2277–2287CrossRefPubMedPubMedCentral
9.
go back to reference 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:e0138841CrossRefPubMedPubMedCentral 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:e0138841CrossRefPubMedPubMedCentral
10.
go back to reference Larsen CP, Cossey LN, Beck LH (2016) THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. Mod Pathol 29:421–426CrossRefPubMedPubMedCentral Larsen CP, Cossey LN, Beck LH (2016) THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. Mod Pathol 29:421–426CrossRefPubMedPubMedCentral
11.
go back to reference 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 31:543–550CrossRefPubMed 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 31:543–550CrossRefPubMed
12.
go back to reference 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 26:2526–2532CrossRefPubMed 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 26:2526–2532CrossRefPubMed
14.
go back to reference 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 19:653–660CrossRefPubMed 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 19:653–660CrossRefPubMed
15.
go back to reference 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 26:257–261CrossRefPubMedPubMedCentral 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 26:257–261CrossRefPubMedPubMedCentral
16.
go back to reference Hofstra JM, Debiec H, Short CD et al (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23:1735–1743CrossRefPubMedPubMedCentral Hofstra JM, Debiec H, Short CD et al (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23:1735–1743CrossRefPubMedPubMedCentral
17.
go back to reference 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 5:8803CrossRefPubMedPubMedCentral 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 5:8803CrossRefPubMedPubMedCentral
18.
go back to reference Ronco P, Debiec H (2012) Pathogenesis of membranous nephropathy: recent advances and future challenges. Nat Rev Nephrol 8:203–213CrossRefPubMed Ronco P, Debiec H (2012) Pathogenesis of membranous nephropathy: recent advances and future challenges. Nat Rev Nephrol 8:203–213CrossRefPubMed
19.
go back to reference 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 57:140–143CrossRefPubMed 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 57:140–143CrossRefPubMed
20.
go back to reference 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 26:709–715CrossRefPubMed 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 26:709–715CrossRefPubMed
21.
go back to reference Ge YC, Jin B, Zeng CH et al (2016) PLA2R antibodies and PLA2R glomerular deposits in psoriasis patients with membranous nephropathy. BMC Nephrol 17:185CrossRefPubMedPubMedCentral Ge YC, Jin B, Zeng CH et al (2016) PLA2R antibodies and PLA2R glomerular deposits in psoriasis patients with membranous nephropathy. BMC Nephrol 17:185CrossRefPubMedPubMedCentral
22.
go back to reference Sharma SG, Larsen CP (2018) Tissue staining for THSD7A in glomeruli correlates with serum antibodies in primary membranous nephropathy: a clinicopathological study. Mod Pathol 31:616–622CrossRefPubMed Sharma SG, Larsen CP (2018) Tissue staining for THSD7A in glomeruli correlates with serum antibodies in primary membranous nephropathy: a clinicopathological study. Mod Pathol 31:616–622CrossRefPubMed
23.
go back to reference 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 12:1642–1651CrossRefPubMedPubMedCentral 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 12:1642–1651CrossRefPubMedPubMedCentral
24.
go back to reference Hayashi N, Okada K, Matsui Y et al (2018) Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy. Nephrol Dial Transplant 33:832–840CrossRefPubMed Hayashi N, Okada K, Matsui Y et al (2018) Glomerular mannose-binding lectin deposition in intrinsic antigen-related membranous nephropathy. Nephrol Dial Transplant 33:832–840CrossRefPubMed
25.
go back to reference Hoxha E, Wiech T, Stahl PR et al (2016) A mechanism for cancer-associated membranous nephropathy. N Engl J Med 374:1995–1996CrossRefPubMed Hoxha E, Wiech T, Stahl PR et al (2016) A mechanism for cancer-associated membranous nephropathy. N Engl J Med 374:1995–1996CrossRefPubMed
Metadata
Title
Circulating antibodies against M-type phospholipase A2 receptor and thrombospondin type-1 domain-containing 7A in Chinese patients with membranous nephropathy
Authors
Caixia Tian
Lian Li
Tanxin Liu
Xin Qu
Yurong Qiu
Publication date
01-08-2019
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 8/2019
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-019-02146-w

Other articles of this Issue 8/2019

International Urology and Nephrology 8/2019 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine