Distribution of glomerular IgG subclass deposits in patients with membranous nephropathy and anti-U1 ribonucleoprotein antibody

Background. The role of IgG subclass in idiopathic membranous nephropathy (IMN) was unclarified. Recent study found IgG subtype switches from IgG1 to IgG4 in the early pathological stage in IMN. The profile of IgG subclass in phospholipase A2 receptor- (PLA2R-) related and PLA2R-unrelated IMN was unrevealed. Our study is aimed at testifying whether IgG subclass switch existed in PLA2R-related and PLA2R-unrelated IMN, respectively. Methods. Our study retrospectively enrolled 157 Chinese patients with biopsy-confirmed IMN between September 2017 and November 2019. We measured glomerular PLA2R antigen and serum anti-PLA2R antibody to classify the patients into PLA2R-related ( n = 132 ) and PLA2R-unrelated ( n = 25 ) subgroup. We evaluated glomerular IgG subclass by immunofluorescence (IF) predominance. Our study defined IgG subclass deposition as predominant if the IF score was higher than the other three and ≥1 +, or as codominant if the IF intensity was equal to any other and ≥1 +. We explored the relationship between IF predominance of glomerular IgG subtype and electron microscopic (EM) stages of IMN. Results. We did not find statistical difference of predominant or codominant rate (pre/co-rate) among EM stages in any subclass ( P > 0.05 ). Pre/co-rate of IgG3 linearly associated with EM stage in total and PLA2R-related subgroup ( P = 0.044 , P = 0.013 ). PLA2R-related subgroup showed higher IgG4 intensity ( 2.1 ± 0.6 vs. 1.6 ± 0.7 , P = 0.001 ) and pre/co-rate of IgG4 in stage 1 (97% vs. 57%, P = 0.015 ) than PLA2R-unrelated group. We found no difference of IgG subclass pre/co-rate in different EM stages or linear association between pre/co-rate of IgG1, IgG2, IgG4, and EM stages ( P > 0.05 ). Conclusions. Pre/co-rate of IgG3 declined with EM stage in total and PLA2R-related subgroup. We did not find IgG subclass switches from IgG1 to IgG4 in either IMN patients or subgroups.

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Epitope Mapping of Human α3(IV)NC1-Induced Membranous Nephropathy in Mice

American Journal of Nephrology ◽

10.1159/000505443 ◽

2020 ◽

Vol 51 (2) ◽

pp. 99-107 ◽

Cited By ~ 1

Author(s):

Jia Wang ◽

Miao Wang ◽

Zhao Cui ◽

Ming-hui Zhao

Keyword(s):

Nephrotic Syndrome ◽

Electron Microscope ◽

Membranous Nephropathy ◽

Epitope Mapping ◽

Igg Subclass ◽

Common Cause ◽

Linear Peptide ◽

Dense Deposits ◽

Circulating Antibodies ◽

Gbm Thickening

Background and Aim: Primary membranous nephropathy (pMN) is the most common cause of nephrotic syndrome in adults. Recent studies suggested that immunization of DBA/1 mice with the main antigen of antiglomerular basement membrane disease (GBM) disease, α3(IV)NC1, could lead to MN lesions. This study aimed to explore the pathogenic epitopes for mouse MN. Methods: Twenty-four linear peptides were synthesized spanning human α3(IV)NC1. Male DBA/1 mice aged 6–8 weeks were immunized with the peptides 200 μg/mouse in Freund’s complete adjuvant subcutaneously and boosted 3 times with the peptides in Freund’s incomplete adjuvant in weeks 3, 5, and 7. The blood and 24-h urine samples were assessed every 2 weeks. The kidneys were examined when the mice were sacrificed at 18 weeks. Results: All the mice immunized with human α3(IV)NC1 and the 24 peptides produced circulating antibodies against the immunogens at 2 weeks and achieved the maximum titers at 8 weeks. About 5/6 (83%) mice immunized with α3(IV)NC1 and (3/6) 50% of the mice immunized with peptide 23 (α3141–154) showed proteinuria at 8–10 weeks and increased continuously. The kidneys showed granular depositions of IgG, C3, and C5b-9 along the glomerular capillary loops. The major IgG subclass was IgG1 (equivalent to human IgG4). GBM thickening with the formation of spikes and subepithelial electron-dense deposits were observed under electron microscope. Conclusion: The linear peptide of α3141–154 could induce clinical and histopathological features of MN in DBA/1 mice, which might give clues to the mechanism of MN in combination with anti-GBM disease.

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Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfg616 ◽

2004 ◽

Vol 19 (3) ◽

pp. 574-579 ◽

Cited By ~ 126

Author(s):

H. Ohtani ◽

H. Wakui ◽

A. Komatsuda ◽

S. Okuyama ◽

R. Masai ◽

...

Keyword(s):

Membranous Nephropathy ◽

Igg Subclass

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Lessons from a rare disease: IgG subclass and disease severity in alloimmune antenatal membranous nephropathy

Kidney International ◽

10.1038/ki.2014.367 ◽

2015 ◽

Vol 87 (3) ◽

pp. 494-497 ◽

Cited By ~ 4

Author(s):

Laurence H. Beck

Keyword(s):

Rare Disease ◽

Disease Severity ◽

Membranous Nephropathy ◽

Igg Subclass

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Genetic homogeneity but IgG subclass–dependent clinical variability of alloimmune membranous nephropathy with anti-neutral endopeptidase antibodies

Kidney International ◽

10.1038/ki.2014.381 ◽

2015 ◽

Vol 87 (3) ◽

pp. 602-609 ◽

Cited By ~ 27

Author(s):

Marina Vivarelli ◽

Francesco Emma ◽

Thimothée Pellé ◽

Christopher Gerken ◽

Stefania Pedicelli ◽

...

Keyword(s):

Membranous Nephropathy ◽

Neutral Endopeptidase ◽

Genetic Homogeneity ◽

Igg Subclass ◽

Clinical Variability

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P0103ANALYSIS OF GLOMERULAR IGG SUBCLASSES SWITCH IN IDIOPATHIC MEMBRANOUS NEPHROPATHY CLASSIFIED BY GLOMERULAR PHOSPHOLIPASE A2 RECEPTOR ANTIGEN AND SERUM ANTIBODY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0103 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Haoyuan Cui ◽

Chao Li ◽

Hang Li ◽

Yu-bing Wen ◽

Xi-wei Yan ◽

...

Keyword(s):

Phospholipase A2 ◽

Membranous Nephropathy ◽

Early Stage ◽

Serum Antibody ◽

Stage I ◽

Chinese Patients ◽

Idiopathic Membranous Nephropathy ◽

Igg Subclass ◽

Phospholipase A2 Receptor ◽

Positive Rate

Abstract Background and Aims IgG subclass switch phenomenon in early pathological stage of idiopathic membranous nephropathy (IMN) was reported recently. However, the profile of serum anti-phospholipase A2 receptor (PLA2R) antibody and glomerular PLA2R antigen was not reported in previous studies. The objective of our study was to testify whether glomerular IgG subclass switch phenomenon was present in PLA2R-related and PLA2R-unrelated IMN, respectively. Method This was a retrospective study including 157 Chinese patients with biopsy-proven IMN in a tertiary referral hospital between September 2017 and November 2019. IMN patients were classified into PLA2R-related (n = 132) and PLA2R-unrelated (n = 25) subgroups. We compared the immunofluorescence intensity of glomerular IgG subclass between two groups among different electron microscopic (EM) stages. Results Positive rate of anti-PLA2R antibody was 56.0% (88/157) and glomerular PLA2R deposition was 75.8% (119/157). The intensity of IgG4 deposition in PLA2R-related group was stronger than that in unrelated group (2.1 ± 0.6 vs. 1.6 ± 0.7, P = 0.001). In stage I, IgG4 showed difference in predominant or co-dominant rate (pre/co rate) between two groups (P = 0.015). IgG4 was predominant in early stage (stage I) of both groups (pre/co rate 97% vs 57%). IgG1 was the less predominant subtype in stage I (pre/co rate 39% vs 43%). Pre/co rate of IgG3 declined with EM stage (P = 0.013). Conclusion IgG subclass switch were not found in PLA2R-related or unrelated IMN. IgG4 was the predominant IgG subtype in all stages of PLA2R-related IMN. The positive rate of glomerular PLA2R antigen was higher than serum PLA2R antibody.

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