Neural Epidermal Growth Factor–Like 1 Protein–Positive Membranous Nephropathy in Chinese Patients

2021 ◽  
pp. CJN.11860720
Author(s):  
Guoqin Wang ◽  
Lijun Sun ◽  
Hongrui Dong ◽  
Yanyan Wang ◽  
Xiaoyi Xu ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinical Characteristics ◽  
Chinese Patients ◽  
Double Positive ◽  
Immunohistochemistry Staining ◽  
Phospholipase A2 Receptor ◽  
Pathologic Features ◽  
Glomerular Deposits ◽  
Epidermal Growth

Background and objectivesThe neural EGF-like 1 (NELL-1) protein is a novel antigen in primary membranous nephropathy. The prevalence and clinical characteristics of NELL-1–positive membranous nephropathy in Chinese individuals with primary membranous nephropathy are unclear.Design, setting, participants, & measurementsA total of 832 consecutive patients with biopsy-proven primary membranous nephropathy were enrolled. The glomerular expression of phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A) was screened. Glomerular immunohistochemistry staining for NELL-1 was performed in 43 patients with PLA2R- and THSD7A-negative membranous nephropathy, 31 patients with PLA2R-positive membranous nephropathy, and two patients with PLA2R and THSD7A double positivity. The NELL-1 antibody was also detected in the sera of patients with NELL-1–positive membranous nephropathy by western blot. Clinical and pathologic features were comparable between patients with isolated NELL-1–positive, isolated PLA2R/THSD7A-positive, and triple antigen–negative membranous nephropathy.ResultsAmong the 832 patients with primary membranous nephropathy, 11 of 54 (20%) patients with PLA2R-negative membranous nephropathy had THSD7A-positive membranous nephropathy. NELL-1–positive membranous nephropathy accounted for 35% (15 of 43) of all patients with PLA2R- and THSD7A-negative membranous nephropathy. One patient was double positive for NELL-1 and PLA2R in glomerular deposits and positive for only the PLA2R antibody in the serum. Most patients with NELL-1–positive membranous nephropathy were women. No tumors were found. There were significant differences in the prevalence of IgG subtypes between patients with different antigen positivity. Among patients with isolated NELL-1–positive membranous nephropathy, although 80% (12 of 15) were IgG4 staining positive, the proportion of IgG4 dominance was only 67% (ten of 15).ConclusionsAbout one third of patients who were PLA2R and THSD7A negative were NELL-1 positive in Chinese patients with primary membranous nephropathy. NELL-1–positive membranous nephropathy was more common than THSD7A-positive membranous nephropathy in PLA2R-negative membranous nephropathy.

Seropositive PLA2R-associated membranous nephropathy but biopsy-negative PLA2R staining

2020 ◽  
Author(s):  
Jiao Luo ◽  
Wang Zhang ◽  
Cailing Su ◽  
Zhanmei Zhou ◽  
Guobao Wang
Keyword(s):  
Membranous Nephropathy ◽  
Interstitial Fibrosis ◽  
Clinicopathological Characteristics ◽  
Enzyme Linked Immunosorbent Assay ◽  
Double Positive ◽  
Lower Serum ◽  
Tubular Atrophy ◽  
Phospholipase A2 Receptor ◽  
Glomerular Deposits ◽  
Paraffin Tissue

Abstract Background Serum phospholipase A2 receptor (PLA2R) antibody (SAb) and glomerular deposits of PLA2R antigen (GAg) have been tested widely in idiopathic membranous nephropathy (MN). Recently, we noticed a special form of PLA2R-associated MN with positive circulating PLA2R antibody but negative PLA2R deposits in the glomeruli by immunofluorescence on frozen tissue (IF-F). The significance of this form of PLA2R-associated MN is yet to be elucidated. This study aimed to explore the clinicopathological features of these PLA2R-associated MN patients. Methods This study enrolled 229 biopsy-proven PLA2R-associated MN patients with SAb+. SAb was measured by enzyme-linked immunosorbent assay, and GAg was detected by IF-F. These patients were divided into SAb+/GAg+ and SAb+/GAg− groups. Clinicopathological characteristics of SAb+/GAg+ and SAb+/GAg− PLA2R-associated MN patients were compared. PLA2R antigens of 19 SAb+/GAg− PLA2R-associated MN patients were verified by immunohistochemistry on paraffin tissue (IHC-P). Results Among 229 SAb+ PLA2R-associated MN patients, 210 (91.70%) were GAg+ and 19 (8.3%) were GAg−. These 19 SAb+/GAg− PLA2R-associated MN patients presented positive PLA2R deposits by IHC-P. Compared with SAb+/GAg+ PLA2R-associated MN patients, SAb+/GAg- PLA2R-associated MN patients had higher levels of serum PLA2R antibody (P = 0.004), increased proteinuria (P = 0.008), lower serum albumin (P = 0.019), more prominent chronic pathological lesions in terms of glomerulosclerosis score (P = 0.025), interstitial fibrosis score (P = 0.016), tubular atrophy score (P = 0.010) and total renal chronicity score (P = 0.010), and were more likely to be accompanied by focal segmental glomerulosclerosis (P = 0.014). Higher SAb level was associated with the total renal chronicity score (odds ratio per 100 RU/mL, 1.16; 95% confidence interval 1.01–1.33; P = 0.033). Conclusions PLA2R-associated MN patients with seropositive PLA2R antibody but negative PLA2R deposits in the glomeruli by IF-F have higher levels of SAb and worse clinicopathological manifestations compared with their double-positive counterparts. IHC-P can be an alternative technique to reveal PLA2R glomerular deposits.

scholarly journals Exostosin 1/Exostosin 2–Associated Membranous Nephropathy

2019 ◽  
Vol 30 (6) ◽  
pp. 1123-1136 ◽  
Author(s):  
Sanjeev Sethi ◽  
Benjamin J. Madden ◽  
Hanna Debiec ◽  
M. Cristine Charlesworth ◽  
LouAnn Gross ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Autoimmune Disease ◽  
Lupus Nephritis ◽  
Membranous Nephropathy ◽  
Validation Cohort ◽  
Laser Microdissection ◽  
Immunohistochemistry Staining ◽  
Phospholipase A2 Receptor ◽  
And Control

BackgroundIn membranous nephropathy (MN), which is characterized by deposition of immune complexes along the glomerular basement membrane (GBM), phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain–containing 7A are target antigens in approximately 70% and 1%–5% of cases of primary MN, respectively. In other cases of primary MN and in secondary MN, the target antigens are unknown.MethodsWe studied 224 cases of biopsy-proven PLA2R-negative MN and 102 controls (including 47 cases of PLA2R-associated MN) in pilot and discovery cohorts. We also evaluated 48 cases of PLA2R-negative presumed primary MN and lupus MN in a validation cohort. We used laser microdissection and mass spectrometry to identify new antigens, which were localized by immunohistochemistry.ResultsMass spectrometry detected exostosin 1 (EXT1) and exostosin 2 (EXT2) in 21 cases of PLA2R-negative MN, but not in PLA2R-associated MN and control cases. Immunohistochemistry staining revealed bright granular GBM staining for EXT1 and EXT2. Clinical and biopsy findings showed features of autoimmune disease, including lupus, in 80.7% of the 26 EXT1/EXT2-associated MN cases we identified. In the validation cohort, we confirmed that EXT1/EXT2 staining was detected in pure class 5 lupus nephritis (eight of 18 patients) and in presumed primary MN associated with signs of autoimmunity (three of 16 patients); only one of the 14 cases of mixed class 5 and 3/4 lupus nephritis was positive for EXT1/EXT2. Tests in seven patients with EXT1/EXT2-associated MN found no circulating anti-exostosin antibodies.ConclusionsA subset of MN is associated with accumulation of EXT1 and EXT2 in the GBM. Autoimmune disease is common in this group of patients.

scholarly journals Retrospective Study of Phospholipase A2 Receptor and IgG Subclasses in Glomerular Deposits in Chinese Patients with Membranous Nephropathy

PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0156263 ◽  
Author(s):  
Hong-rui Dong ◽  
Yan-yan Wang ◽  
Xiao-hong Cheng ◽  
Guo-qing Wang ◽  
Li-jun Sun ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Igg Subclasses ◽  
Chinese Patients ◽  
Phospholipase A2 Receptor ◽  
Glomerular Deposits

Routine immunohistochemical staining in membranous nephropathy: in situ detection of phospholipase A2 receptor and thrombospondin type 1 containing 7A domain

2018 ◽  
Vol 31 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Vincenzo L’Imperio ◽  
Federico Pieruzzi ◽  
Renato Alberto Sinico ◽  
Manuela Nebuloni ◽  
Antonio Granata ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Membranous Nephropathy ◽  
Immunohistochemical Staining ◽  
Phospholipase A2 Receptor ◽  
In Situ Detection

scholarly journals Membranous nephropathy associated with viral infection

2020 ◽  
Author(s):  
Aikaterini Nikolopoulou ◽  
Catarina Teixeira ◽  
H Terry Cook ◽  
Candice Roufosse ◽  
Thomas H D Cairns ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Viral Infection ◽  
Membranous Nephropathy ◽  
Spontaneous Remission ◽  
Outcome Data ◽  
Phospholipase A2 Receptor ◽  
B Virus ◽  
Immunodeficiency Virus ◽  
Hepatitis Infection

Abstract Background Membranous nephropathy (MN) can be associated with hepatitis infection and less commonly with human immunodeficiency virus (HIV) infection. The significance of anti-phospholipase A2 receptor (PLA2R) and anti-thrombospondin type 1 domain-containing 7A (THSD7A) antibodies in this setting is unclear. Methods We describe the clinical, histopathological and outcome data of 19 patients with MN and hepatitis B virus (HBV), hepatitis C virus (HCV) or HIV infection identified through our renal biopsy database and the association with anti-PLA2R antibodies and anti-THSD7A antibodies. Results The cohort consisted of 19 patients, 8 male and 11 female, with a median age of 42 years (range 23–74). HBV infection was found in six cases, HCV in four and HIV in nine (two HIV patients had HBV co-infection and one HCV co-infection). PLA2R staining on biopsy was positive in 10/19 patients: 4 with HBV-MN, 3 with HCV-MN and 3 with HIV-MN and circulating anti-PLA2R antibodies were detected in 7/10 cases. THSD7A staining on biopsy was positive in three PLA2R-negative cases, one with HBV-MN and two with HIV-MN. Mean proteinuria was higher in the PLA2R-positive group and the median urinary protein:creatinine ratio (uPCR) was 963 mg/mmol (range 22–2406) compared with the PLA2R-negative group [median uPCR 548 mg/mmol (range 65–1898); P = 0.18 Mann–Whitney]. Spontaneous remission occurred in 6/19 patients and after-treatment remission occurred in 7/11 patients. Renal function was preserved in all but two patients who required haemodialysis 2 and 11 years from diagnosis. Conclusions We describe a cohort of patients with MN associated with viral infection, including rare cases of HIV-MN with PLA2R and THSD7A positivity. The mechanism of coincidental or viral-related MN needs to be investigated further.

scholarly journals Serum Antibody and Glomerular Antigen of Antiphospholipase A2 Receptor in Chinese Patients with Idiopathic Membranous Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Qiu-hua Zhang ◽  
Mian Wu ◽  
Zhi-gang Hu ◽  
Xiao-bin Liu ◽  
Biao Huang ◽  
...  
Keyword(s):  
Renal Function ◽  
Serum Creatinine ◽  
Serum Albumin ◽  
Membranous Nephropathy ◽  
Serum Antibody ◽  
Chinese Patients ◽  
Idiopathic Membranous Nephropathy ◽  
Phospholipase A2 Receptor ◽  
Secondary Membranous Nephropathy ◽  
Clinical Correlations

Background. M-type phospholipase A2 receptor (PLA2R) is the first autoantigen responsible for idiopathic membranous nephropathy (IMN). However, serum PLA2R antibody (PLA2R-Ab) can be inaccurate in distinguishing between IMN and secondary membranous nephropathy, while renal PLA2R antigen (PLA2R-Ag) emerges as an ancillary diagnostic. The present study is aimed at examining the associations between PLA2R-Ab in sera and PLA2R-Ag in kidneys in IMN patients. Methods. A total of 93 patients with IMN were retrospectively identified. Their serum PLA2R-Ab and renal PLA2R-Ag expression levels were determined, and the clinical correlations between these parameters and clinical features were examined. Results. The sensitivities of serum PLA2R-Ab and renal PLA2R-Ag for diagnosing IMN were 74.2% and 88.2%, respectively (P<0.001), with poor consistency. Higher serum PLA2R-Ab levels were correlated to stronger renal PLA2R-Ag expression (P=0.048). Patients with positive PLA2R-Ab significantly differed from those with negative levels, in terms of proteinuric levels over 24 hours (4.54 vs. 3.46 g/day, P=0.015) and serum albumin (23.28 vs. 27.95 g/L, P=0.038). Among patients with positive renal PLA2R-Ag, patients with positive PLA2R-Ab had significantly higher 24-hour proteinuria, when compared to patients with negative PLA2R-Ab (4.57 vs. 3.08 g/day, P=0.005). Among those with positive PLA2R-Ab in sera, their PLA2R-Ab levels were correlated with the estimated glomerular filtration and serum creatinine. Conclusion. Serum PLA2R-Ab exhibits a closer correlation with proteinuric severity and renal function, when compared to renal PLA2R-Ag.

scholarly journals Clinicopathological features in membranous nephropathy with cancer: A retrospective single-center study and literature review

2019 ◽  
Vol 34 (4) ◽  
pp. 406-413
Author(s):  
Dan Zhang ◽  
Chong Zhang ◽  
Fan Bian ◽  
Wenzhu Zhang ◽  
Gengru Jiang ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Clinicopathological Characteristics ◽  
Idiopathic Membranous Nephropathy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Patients With Cancer ◽  
Phospholipase A2 Receptor ◽  
Single Center Study ◽  
Close Relationship ◽  
Circulating Antibodies

Background: Membranous nephropathy is the most common glomerular disease related to malignancy. However, it is difficult to distinguish between true malignancy-related membranous nephropathy and idiopathic membranous nephropathy coincident with cancer. It has been reported that phospholipase A2 receptor (PLA2R) is the first autoantigen involved in idiopathic membranous nephropathy and thrombospondin type-1 domain-containing 7A (THSD7A) may have a close relationship with malignancy-related membranous nephropathy. Therefore, the aim of this study was to compare the clinicopathological characteristics between membranous nephropathy patients with cancer and idiopathic membranous nephropathy patients without cancer to better detect malignancy-related membranous nephropathy, including glomerular PLA2R and THSD7A depositions and their circulating antibodies, together with glomerular IgG4 deposition. Methods: Twelve membranous nephropathy patients with cancer and 257 idiopathic membranous nephropathy patients without cancer were included in this study and had been followed up for more than 1 year. The glomerular expression of PLA2R, THSD7A, and IgG4 was analyzed by immunohistochemistry. Circulating anti-PLA2R and anti-THSD7A antibodies were assessed by enzyme-linked immunosorbent assay and indirect immunofluorescence testing, respectively. Results: Membranous nephropathy patients with cancer were significantly older and had higher serum creatinine and a lower estimated glomerular filtration rate than idiopathic membranous nephropathy patients ( P<0.05). The positive rates of glomerular PLA2R and IgG4 depositions and circulating anti-PLA2R antibodies in membranous nephropathy patients with cancer were significantly lower than those in idiopathic membranous nephropathy patients without cancer ( P<0.01). Conclusion: The absence of glomerular PLA2R deposition and negative circulating anti-PLA2R antibodies, along with negative glomerular IgG4 staining, may be useful clues to more accurately screen underlying malignancies in membranous nephropathy patients.

Sign in / Sign up

Export Citation Format

Share Document