Renal Phospholipase A&lt;sub&gt;2&lt;/sub&gt; Receptor in Hepatitis B Virus-Associated Membranous Nephropathy

Xie, Qionghong; Li, Yan; Xue, Jun; Xiong, Zhenggang; Wang, Liang; Sun, Zhonghua; Ren, Yueheng; Zhu, Xiaoye; Hao, Chuan‐Ming

doi:10.1159/000431331

Cited by 119 publications

(90 citation statements)

References 21 publications

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“…Circulating PLA2R antibodies seem to be specific for pMN [32-34]; however, they can also occur in secondary MN, especially the hepatitis B virus-related MN common in China [35]. The prevalence of positive antibodies varies between different diagnostic centers, from the highest prevalence of 82% [36] to the lower prevalences of 68% [37], 59% [38], and 69% [39], respectively, in China.…”

Section: The Autoimmune Disorders Of Pmnmentioning

confidence: 99%

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

2018

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Background: Primary membranous nephropathy (pMN) is the most common cause of nephrotic syndrome in adults. The discovery of the 2 autoantigens, M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A), has defined pMN as an autoimmune disease. A remarkable increase in the frequency of pMN in primary glomerular disease was witnessed in China. The genetic and environmental contributors to disease susceptibility have been investigated in these patients. Summary: We reviewed recent publications in genetic and environmental studies of pMN, focusing mainly on those undertaken in China. Following a genome-wide association study, the gene-gene interaction between the 2 most significant risk factors, PLA2R1 and DQA1, was validated in Chinese patients with MN. Fine mapping on human leukocyte antigen (HLA) locus found that DRB1*1501 and DRB1*0301 were risk alleles. Three amino acid residues on positions 13 and 71 of HLA-DRβ1 chain may confer the susceptibility to pMN by presenting T-cell epitopes on PLA2R. Another study found that DRB3*0202 was the most likely culprit allele for the signal at DRB1*0301. One environmental risk factor for pMN has been identified as the long-term exposure to high levels of PM_2.5 in Chinese patients with MN. Each 10 μg/m³ increase in PM_2.5 concentration was associated with 14% higher odds for pMN in the regions with PM_2.5 above 70 μg/m³. Key Message: A gene-environment interaction is suspected as an underlying mechanism for the increasing trend of pMN in China.

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Section: The Autoimmune Disorders Of Pmnmentioning

confidence: 99%

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

2018

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“…Glomerular depositions of PLA2R have been thought as specific findings of IMN. However, the significance of PLA2R for differentiation of IMN from HBV-MN is controversial because co-localized deposition with HBsAg has been reported from China (4). In the present case, we performed double immunofluorescence study with both of the antibodies against HBs-Ag and PLA2R, and found the co-localized deposition of them shown along the glomerular capillary walls.…”

Section: Discussionmentioning

confidence: 51%

“…However, the role of PLA2R in patients with HBV-MN is still unclear in Asian countries. Frequent co-localization of PLA2R and HBV antigens are reported mainly from China (4). We report the case of PLA2R-positive HBV-MN that was remitted with entecavir after a relapse during the treatment with lamivudine.…”

Section: Introductionmentioning

confidence: 89%

Anti-phospholipase A2 receptor antibody positive hepatitis B virus-associated membranous nephropathy remitted with entecavir after relapse with lamivudine

Sasaki¹,

Nagai²,

Mikami³

et al. 2017

J Nephropathol

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Background: Phospholipase A2 receptor (PLA2R) is thought to be an intrinsic antigen of idiopathic membranous nephropathy (IMN), and has been widely used for the differentiation from secondary membranous nephropathies. However, the positive expression of PLA2R in the patients with hepatitis B virus associated membranous nephropathy (HBV-MN) is controversial in Asian countries, because co-localization of PLA2R and HBV antigens in glomeruli have been reported. Case Presentation: We report a case of anti PLA2R antibody positive HBV-MN that was remitted with entecavir after a relapse during treatment with lamivudine. In a renal biopsy of the case, we could confirm the co-localized glomerular deposition of HBV surface antigen (HBs-Ag) and PLA2R using double staining of immunofluorescence. We also could observe the relapse of nephrotic syndrome correlated with the increased titer of HBs-Ag, and the remission with the decrease of HBs-Ag by the change of antiviral agents. Conclusions: Our case demonstrated that the renal manifestation of HBV-MN clearly responded to antiviral agents. Furthermore, the co-localized glomerular depositions of PLA2R and HBs-Ag in HBV-MN may be concerned with the etiology of MN patients with chronic HBV infection.

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“…Although initial reports showed ,5% of patients with HBVassociated MN having a positive assay for anti-PLA2R (12), a recent study indicated contradictory findings with 64% of HBV patients showing anti-PLA2R (13). The study also demonstrated the presence of HBV antigens colocalizing with anti-PLA2R antibody confirming the possible association of these two findings.…”

Section: Membranous Nephropathymentioning

confidence: 52%

Viral-Associated GN: Hepatitis B and Other Viral Infections

Kupin

2016

CJASN

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By definition, viral-associated GN indicates the direct pathogenic relationship between active viral replication and the development of acute GN. This definition is in sharp contrast to the semantic label and pathophysiologic foundation behind postinfectious GN that uniquely develops only during a period of resolved and absent active infection. The primary example of postinfectious GN are the glomerular lesions described after a pharyngeal or cutaneous streptococcal infection and do not represent the clinical or immunologic pattern seen with viralassociated GN. Hepatitis B (HBV) is the most common chronic viral infection in the world affecting >400 million people which is more than double the prevalence of chronic HIV and hepatitis C carriers combined. In addition, 10%-20% of HBV patients may be coinfected with hepatitis C and 5%-10% will have coinfection with HIV. Being able to distinguish the different types of GN seen with each viral infection is essential for the practicing clinician as each virus requires its own specific antiviral therapy. HBV-induced immune complex disease with renal injury lies on one end of the spectrum of disorders that occurs after a prolonged chronic carrier state. On the opposite end of the spectrum are renal diseases that develop from acute or subacute viral infections. One important glomerular lesion in this category is the association of collapsing FSGS with acute active cytomegalovirus, Epstein-Barr virus, and parvovirus B19 infection. The data supporting or disproving this relationship for each of these viruses will be discussed. A second renal manifestation of acute viral infections often occurs with many different sporadic or epidemic infections such as dengue and hantavirus and can lead to a transient proliferative GN that resolves upon viral clearance. The complex interplay of HBV and all viruses with the immune system provides conceptual lessons on the pathophysiology of immune complex GN that can be applied to all infection-related renal disease and plays an integral role in developing an approach to therapeutic intervention.

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Renal Phospholipase A<sub>2</sub> Receptor in Hepatitis B Virus-Associated Membranous Nephropathy

Cited by 119 publications

References 21 publications

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

The Genetic and Environmental Factors of Primary Membranous Nephropathy: An Overview from China

Anti-phospholipase A2 receptor antibody positive hepatitis B virus-associated membranous nephropathy remitted with entecavir after relapse with lamivudine

Viral-Associated GN: Hepatitis B and Other Viral Infections

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