Determination of Anti-Phospholipase A2 and Anti-Thrombospondin Type 1 Domain-Containing Protein 7A in Latin Patients With Membranous Nephropathy

Author(s):  
L. C. Battaini ◽  
O. T. Ranzani ◽  
L. J. Marçal ◽  
L. Antonangelo ◽  
L.B. Jorge ◽  
...  

Abstract BACKGROUND Membranous nephropathy (MN) is caused by antibodies against podocyte antigens, of which the type M receptor of phospholipase A2 (PLA2R) and thrombospondin type-1 domain containing 7 A (THSD7A) are the mostly studied. The objectives of this study were to determine anti-PLA2R and anti-THSD7A serum antibodies and anti-PLA2R renal tissue prevalence in a Latin population with primary MN and to evaluate their role as biomarkers for disease activity. Additionally, the performance of the two available serum diagnostic methods - ELISA and indirect immunofluorescence - was evaluated for the diagnosis of MN. METHODS Fifty-nine patients, 29 MN, 18 lupus membranous nephropathy (LMN) and 12 focal and segmental glomerulosclerosis (FSGS) were evaluated for serum antibodies. Renal biopsies were also evaluated for the presence of anti-PLA2R. Twenty-one patients with MN were followed for 1 year. RESULTS Patients with LMN and FSGS were negative for both antibodies. All 29 MN were negative for anti-THSD7A; 16 MN were positive by ELISA and/or IFI, and 3 MN patients were positive only by IFI. Thus, ELISA test showed a 45% sensitivity and 97% specificity while the IFI showed a 55% and 100%, respectively. In patients with less than a year between biopsy and antibody collection, sensitivity increased to 79% and maintained specificity. Positive correlations were observed between the anti-PLA2R ELISA titer and proteinuria. Among the 28 MN renal biopsies, 20 presented anti-PLA2R positive staining, a 72% sensitivity. CONCLUSIONS The determination of anti-PLA2R antibodies in the Latin population showed similar rates as reported in other populations, and the IFI test presented greater sensitivity. A lower rate of remission was found among those with anti-PLA2R positive tests.

2019 ◽  
Vol 72 (10) ◽  
pp. 705-711 ◽  
Author(s):  
Changming Zhang ◽  
Mingchao Zhang ◽  
Dacheng Chen ◽  
Qiang Ren ◽  
Weiwei Xu ◽  
...  

AimsPhospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were identified as pathogenic antigens in patients with membranous nephropathy (MN). Notably, PLA2R is detected in few patients with malignancy-associated MN, and a high incidence of cancer is reported in patients with THSD7A-associated MN. Therefore, the roles of PLA2R and THSD7A in malignancy-associated MN must be clarified.MethodsSerum anti-PLA2R antibodies and glomerular PLA2R staining were assessed in 36 patients with malignancy-associated MN, followed by examination of serum anti-THSD7A antibodies and glomerular THSD7A. THSD7A staining in cancer tissues was also assessed in 9 of the 36 patients.ResultsTwelve (33%) of 36 patients were positive for both glomerular PLA2R and serum anti-PLA2R antibodies, one of whom had enhanced glomerular THSD7A staining. Two patients were positive for either glomerular PLA2R or serum anti-PLA2R antibody. All these patients had IgG4-dominant deposits in glomeruli. Among the 22 (61%) patients who were double negative for glomerular PLA2R and serum anti-PLA2R antibodies, 17 of 20 (85%) had IgG1-dominant deposits in glomeruli, and 2 (9.1%) were positive for glomerular THSD7A staining. Serum anti-THSD7A antibody was not detected in any of the 36 patients. Among the nine patients with available cancer tissues, positive staining of THSD7A in the cancer tissues was observed in five (56%) patients, and one showed enhanced glomerular staining of THSD7A.ConclusionsScreening of glomerular PLA2R antigen and serum anti-PLA2R antibodies is necessary in patients with malignancy-associated MN, whereas the incidence of glomerular THSD7A antigen or circulating anti-THSD7A antibodies is uncommon.


2021 ◽  
Author(s):  
ting li ◽  
qingqing wu ◽  
Xue Yang ◽  
Yueming liu ◽  
bo lin ◽  
...  

Background: The level of serum antibodies against the M-type phospholipase A2 receptor (anti-PLA2R-IgG) is closely related to the disease activity of idiopathic membranous nephropathy (IMN). Therefore, the establishment of a...


2018 ◽  
Vol 31 (4) ◽  
pp. 543-550 ◽  
Author(s):  
Vincenzo L’Imperio ◽  
Federico Pieruzzi ◽  
Renato Alberto Sinico ◽  
Manuela Nebuloni ◽  
Antonio Granata ◽  
...  

2019 ◽  
Vol 12 (1) ◽  
pp. 27-32
Author(s):  
Yosuke Inaguma ◽  
Atsutoshi Shiratori ◽  
Taku Nakagawa ◽  
Kyoko Kanda ◽  
Makiko Yoshida ◽  
...  

Background: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome in adults that can also occur in children, albeit less frequently. Recently, the M-type phospholipase A2 receptor (PLA2R) was identified as the target antigen in idiopathic membranous nephropathy (IMN), making it a useful marker for diagnosis. However, there are few studies describing the potential role of PLA2R in children with IMN. The aim of this study was to clarify the involvement of PLA2R in childhood IMN. Methods: We enrolled 11 patients diagnosed with IMN from January 1998 to March 2017. We performed PLA2R staining in paraffin-embedded renal biopsy sections. The clinical data were collected from the patients’ medical records. Results: The median age at biopsy was 6 years (range, 4 to 14 years). A single 6-year-old boy among all pediatric patients with IMN had granular PLA2R staining along his glomerular capillary loops and the prevalence of PLA2R-positivity was 9%. He also showed IgG4 co-dominant staining in terms of IgG subclass. There were no apparent differences in his clinical features such as clinical data at the time of renal biopsy, the time from the treatment initiation to remission, and relapse or renal dysfunction during the follow-up period. Conclusion: We suggest that PLA2R staining can be a diagnostic tool for patients with IMN of any age, though pediatric patients with IMN have lower prevalence of PLA2R-positive staining than adult patients.


2013 ◽  
Vol 421 ◽  
pp. 213-218 ◽  
Author(s):  
Cornelia Dähnrich ◽  
Lars Komorowski ◽  
Christian Probst ◽  
Barbara Seitz-Polski ◽  
Vincent Esnault ◽  
...  

2020 ◽  
Vol 58 (8) ◽  
pp. 1357-1364 ◽  
Author(s):  
Marie Tré-Hardy ◽  
Alain Wilmet ◽  
Ingrid Beukinga ◽  
Jean-Michel Dogné ◽  
Jonathan Douxfils ◽  
...  

AbstractObjectivesFaced with the COVID-19 pandemic and its impact on the availability and quality of both therapeutic and diagnostic methods, the Belgian authorities have decided to launch a procedure for additional evaluation of the performance of serological tests offered for sale on the national territory. This has been proposed with a double aim: (1) an in-depth verification of the analytical and clinical performances presented by the manufacturer and (2) an economy of scale in terms of centralized validation for all the laboratories using the tests subject to evaluation.MethodsA retrospective validation study was conducted including the serum of 125 patients in order to determine the analytical and clinical performances of the LIAISON®SARS-CoV-2 from DiaSorin® detecting anti-SARS-CoV-2 IgG and to compare its clinical performance with the enzyme-linked immunosorbent assay (ELISA) test from Euroimmun®, one of the first commercially available tests allowing the detection of anti-SARS-CoV-2 IgA and IgG.ResultsThe performances of the LIAISON®SARS-CoV-2 satisfied all the acceptance criteria and provided “real world” analytical and clinical performances very close to the ones reported by the manufacturer in its insert kit. Comparison between the LIAISON®SARS-CoV-2 and the ELISA method did not reveal any difference between the two techniques in terms of sensitivities and specificities regarding the determination of the IgG.ConclusionsThis study reports the validation of the LIAISON®SARS-CoV-2 allowing to detect IgG antibodies specifically directed against SARS-CoV-2. The analytical and clinical performances are excellent, and the automation of the test offers important rates, ideal for absorbing an extension of testing.


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