Membranous nephropathy and cancer in the era of PLA2R testing

2018 ◽  
Vol 2 (2-3) ◽  
pp. 50-55 ◽  
Author(s):  
Pascale Khairallah ◽  
Andrew Bomback
Keyword(s):  
Cancer Screening ◽  
General Population ◽  
Membranous Nephropathy ◽  
Phospholipase A ◽  
Idiopathic Membranous Nephropathy ◽  
Antibody Testing ◽  
Risk Of Malignancy ◽  
Major Antigen

Membranous nephropathy has historically been associated with a higher risk of malignancy compared to the general population. Following a membranous nephropathy diagnosis, physicians screen patients for underlying cancers at the time of and up to several years following the diagnosis. The discovery of phospholipase A2 receptor (PLA2R) as a major antigen in primary membranous nephropathy may be changing how we think about the association between membranous nephropathy and cancer. PLA2R was found to be present in 72% of cases of idiopathic membranous nephropathy with very few PLA2R patients having cancer. Following PLA2R discovery, thrombospondin type-1 domain-containing 7A (THSD7A) was discovered. This antigen, in contrast to PLA2R, may be more strongly associated with cancer. This review will evaluate the associations between these antigens and cancer, as well as propose an algorithm on cancer screening in the era of antibody testing.

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.

scholarly journals Thrombospondin Type-1 Domain-Containing 7A in Idiopathic Membranous Nephropathy

2014 ◽  
Vol 371 (24) ◽  
pp. 2277-2287 ◽  
Author(s):  
Nicola M. Tomas ◽  
Laurence H. Beck ◽  
Catherine Meyer-Schwesinger ◽  
Barbara Seitz-Polski ◽  
Hong Ma ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Idiopathic Membranous Nephropathy

scholarly journals Integrative analysis of miRNA–mRNA network in idiopathic membranous nephropathy by bioinformatics analysis

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12271
Author(s):  
Wenfang He ◽  
Jinshi Zhang ◽  
Shizhu Yuan ◽  
Mingzhu Liang ◽  
Weidong Chen ◽  
...  
Keyword(s):  
Membranous Nephropathy ◽  
Regulatory Networks ◽  
Target Genes ◽  
Therapeutic Targets ◽  
Differentially Expressed ◽  
Idiopathic Membranous Nephropathy ◽  
Validation Dataset ◽  
Epidermal Growth ◽  
Specific Antigens

Background Currently, several specific antigens, M-type receptor for secretory phospholipase A2(PLA2R1), thrombospondin type-1 domain-containing 7A(THSD7A), and neural epidermal growth factor-like 1 protein (NELL-1), are discovered associated with the onset of idiopathic membranous nephropathy (IMN). But the pathomechanisms of IMN still need to be further claried. Understanding the mechanisms of IMN is required to improve its diagnosis and treatment. Methods In this study, we constructed miRNA regulatory networks to investigate IMN development. Moreover, miRNAs and mRNAs that were differentially expressed between Idiopathic Membranous Nephropathy (IMN) patients and normal controls were examined using the GSE115857 dataset and our previous sequence study. DE miRNA target genes were determined based on the FUNRICH software, starBase, miRDB, and miRWalk, and an miRNA-mRNA network was designed using DE-mRNAs that were negatively correlated with DE-miRNAs. The miRNA-mRNA network contained 228 miRNA-mRNA pairs. Thereafter, we conducted KEGG pathway, GO functional annotation, immune-related gene screening, protein interaction networks, and potential hub gene analyses. Furthermore, 10 miRNAs and 10 genes were determined and preliminarily validated using the validation dataset from GEO. Finally, we identified which pair may offer more accurate diagnosis and therapeutic targets for IMN. Results Two miRNA-mRNA pairs, miR-155-5p-FOS and miR-146a-5p-BTG2, were differentially expressed in IMN, indicating that these genes may affect IMN through immune processes. These findings may offer more accurate diagnoses and therapeutic targets for IMN.

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