A cohort study of membranous nephropathy, primary or secondary

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Abstract

Background

Although IgG4 deposit against phospholipase A2 receptor (anti-PLA2R) is predominantly presented in the renal biopsy of patients with primary membranous nephropathy (MN), its diagnostic value of this immune complex has not been fully established.

Methods

In this cohort study, 108 biopsy-proven MN patients with proteinuria were evaluated during two years follow up and were divided into primary and secondary groups. Renal biopsy specimens were pathologically assessed for IgG4 and PLA2R depositions by immunohistochemistry (IHC). Therefore, the relationships between staining severity, MN type and total proteinuria in all patients were determined.

Results

Of 108 patients, 73.1% had primary MN and 26.9% were diagnosed as secondary form. IHC staining in patients with primary MN was positive for PLA2R in 76 (96.2%) and IgG4 in 68 (86.1%). Cases with positive PLA2R expression had a significantly higher rate among patients with mild to moderate stages ( P = 0.03). No significant relationship was found between intensity of PLA2R and IgG4 deposits with proteinuria and serum creatinine. Based on our data, double positivity/negativity of PLA2R and IgG4 expression adds prominent information to the clinical data and were found to be useful and robust biomarkers for detection of primary MN patients with high sensitivity and specificity (97.1 and 96.3% respectively, PPV = 98.5% and NPV = 92.9%).

Conclusions

Simultaneously expression of PLA2R and IgG4 in renal biopsy specimens of patients with MN could possibly be used as a potential diagnostic method to distinguish primary from secondary MN and also pathological severity of the disease.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12882-021-02338-6.

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Most cited references 34

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Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

Michelle Petri, Ana-Maria Orbai, Graciela Alarcón … (2012)

The Systemic Lupus International Collaborating Clinics (SLICC) group revised and validated the American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria in order to improve clinical relevance, meet stringent methodology requirements, and incorporate new knowledge regarding the immunology of SLE. The classification criteria were derived from a set of 702 expert-rated patient scenarios. Recursive partitioning was used to derive an initial rule that was simplified and refined based on SLICC physician consensus. The SLICC group validated the classification criteria in a new validation sample of 690 new expert-rated patient scenarios. Seventeen criteria were identified. In the derivation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (49 versus 70; P = 0.0082) and had greater sensitivity (94% versus 86%; P < 0.0001) and equal specificity (92% versus 93%; P = 0.39). In the validation set, the SLICC classification criteria resulted in fewer misclassifications compared with the current ACR classification criteria (62 versus 74; P = 0.24) and had greater sensitivity (97% versus 83%; P < 0.0001) but lower specificity (84% versus 96%; P < 0.0001). The new SLICC classification criteria performed well in a large set of patient scenarios rated by experts. According to the SLICC rule for the classification of SLE, the patient must satisfy at least 4 criteria, including at least one clinical criterion and one immunologic criterion OR the patient must have biopsy-proven lupus nephritis in the presence of antinuclear antibodies or anti-double-stranded DNA antibodies. Copyright © 2012 by the American College of Rheumatology.

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M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.

Gérard Lambeau, Ramon G. Bonegio, Judith Beck … (2009)

Idiopathic membranous nephropathy, a common form of the nephrotic syndrome, is an antibody-mediated autoimmune glomerular disease. Serologic diagnosis has been elusive because the target antigen is unknown. We performed Western blotting of protein extracts from normal human glomeruli with serum samples from patients with idiopathic or secondary membranous nephropathy or other proteinuric or autoimmune diseases and from normal controls. We used mass spectrometry to analyze the reactive protein bands and confirmed the identity and location of the target antigen with a monospecific antibody. Serum samples from 26 of 37 patients (70%) with idiopathic but not secondary membranous nephropathy specifically identified a 185-kD glycoprotein in nonreduced glomerular extract. Mass spectrometry of the reactive protein band detected the M-type phospholipase A(2) receptor (PLA(2)R). Reactive serum specimens recognized recombinant PLA(2)R and bound the same 185-kD glomerular protein as did the monospecific anti-PLA(2)R antibody. Anti-PLA(2)R autoantibodies in serum samples from patients with membranous nephropathy were mainly IgG4, the predominant immunoglobulin subclass in glomerular deposits. PLA(2)R was expressed in podocytes in normal human glomeruli and colocalized with IgG4 in immune deposits in glomeruli of patients with membranous nephropathy. IgG eluted from such deposits in patients with idiopathic membranous nephropathy, but not in those with lupus membranous or IgA nephropathy, recognized PLA(2)R. A majority of patients with idiopathic membranous nephropathy have antibodies against a conformation-dependent epitope in PLA(2)R. PLA(2)R is present in normal podocytes and in immune deposits in patients with idiopathic membranous nephropathy, indicating that PLA(2)R is a major antigen in this disease. 2009 Massachusetts Medical Society

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The classification of glomerulonephritis in systemic lupus erythematosus revisited.

Lai-Meng Looi, Michio Nagata, Robert G. Hill … (2004)

The currently used classification reflects our understanding of the pathogenesis of the various forms of lupus nephritis, but clinicopathologic studies have revealed the need for improved categorization and terminology. Based on the 1982 classification published under the auspices of the World Health Organization (WHO) and subsequent clinicopathologic data, we propose that class I and II be used for purely mesangial involvement (I, mesangial immune deposits without mesangial hypercellularity; II, mesangial immune deposits with mesangial hypercellularity); class III for focal glomerulonephritis (involving or = 50% of total number of glomeruli) either with segmental (class IV-S) or global (class IV-G) involvement, and also with subdivisions for active and sclerotic lesions; class V for membranous lupus nephritis; and class VI for advanced sclerosing lesions]. Combinations of membranous and proliferative glomerulonephritis (i.e., class III and V or class IV and V) should be reported individually in the diagnostic line. The diagnosis should also include entries for any concomitant vascular or tubulointerstitial lesions. One of the main advantages of the current revised classification is that it provides a clear and unequivocal description of the various lesions and classes of lupus nephritis, allowing a better standardization and lending a basis for further clinicopathologic studies. We hope that this revision, which evolved under the auspices of the International Society of Nephrology and the Renal Pathology Society, will contribute to further advancement of the WHO classification.

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Author and article information

Contributors

Maryam Arghiani: ArghianiM@mums.ac.ir

Boshra Hasan Zamani: HasanzamaniB@mums.ac.ir

Fatemeh Nazemian: NazemianF@mums.ac.ir

Sara Samadi: Samadis931@mums.ac.ir

Malihe Saber Afsharian: saberafsharian@yahoo.com

Mahmoud Habibzadeh: sm_Habibzadeh@yahoo.com

Saeid Eslami: sabbaghm@mums.ac.ir

Mahin Ghorban Sabbagh: sabbaghm@mums.ac.ir

Journal

Journal ID (nlm-ta): BMC Nephrol

Journal ID (iso-abbrev): BMC Nephrol

Title: BMC Nephrology

Publisher: BioMed Central (London )

ISSN (Electronic): 1471-2369

Publication date (Electronic): 19 April 2021

Publication date PMC-release: 19 April 2021

Publication date Collection: 2021

Volume: 22

Electronic Location Identifier: 138

Affiliations

[1 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Kidney Transplantation Complications Research Center, , Mashhad University of Medical Sciences, ; Mashhad, Iran

[2 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Student research committee, , Mashhad University of Medical Sciences, ; Mashhad, Iran

[3 ]GRID grid.411768.d, ISNI 0000 0004 1756 1744, Islamic Azad University, Mashhad Branch, ; Mashhad, Iran

[4 ]Razi pathology and genetic lab, Rasht, Iran

[5 ]GRID grid.411583.a, ISNI 0000 0001 2198 6209, Department of medical informatics, Faculty of Medicine, , Mashhad University of Medical Sciences, ; Mashhad, Iran

Article

Publisher ID: 2338

DOI: 10.1186/s12882-021-02338-6

PMC ID: 8056567

PubMed ID: 33874909

SO-VID: 9824e9a4-b99a-4385-91de-836fdc1291e6

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 14 October 2020

Date accepted : 5 April 2021

Custom metadata

ScienceOpen disciplines: Nephrology

Keywords: membranous nephropathy,phospholipase a2 receptor,pla2r,igg4,primary mn,secondary mn

Data availability:

ScienceOpen disciplines: Nephrology

Keywords: membranous nephropathy, phospholipase a2 receptor, pla2r, igg4, primary mn, secondary mn

A cohort study of membranous nephropathy, primary or secondary

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Abstract

Background

Methods

Results

Conclusions

Supplementary Information

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Karger: Nephrology

Most cited references 34

Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus.

M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy.

The classification of glomerulonephritis in systemic lupus erythematosus revisited.

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