Defect of Cell-Mediated Immune Response against Hepatitis B Virus; An Indication for Pathogenesis of Hepatitis-B-Virus-Associated Membranous Nephropathy

Lin, Ching-Yuang; Lin, Chiou-Chyn; Chang, Gwong‐Jen J.; King, Chwan-Chuen

doi:10.1159/000190166

Cited by 21 publications

(17 citation statements)

References 7 publications

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“…The pathogenesis of HBV-associated GN is not fully understood [2,16]. The demonstration of HBsAg and HBeAg in the glomerular deposits suggests an immune complex mechanism leading to glomerular injury.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, it has been demonstrated that patients with HBVrelated MGN had an inadequate cellular immune response to HBeAg, causing defective clearance of virus particles and virus-infected cells [16]. Thus, the free form of HBeAg is filtered and deposited in the subepithelial zone of the GBM where it combines with antiHBe antibody, leading to HBV-related membranous nephropathy.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children

Özdamar

Güçer

Tinaztepe

2003

Pediatric Nephrology

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Hepatitis B virus (HBV)-associated glomerulonephritides have been increasingly reported, and the association between HBV and glomerulopathy is striking, especially in children. In this study, we investigated clinical and immunohistological features of HBV-associated glomerulonephritis in 14 children aged from 2.5 to 16 years (mean 10 years). The nephrotic syndrome was present in 9 (64%) and the nephritic syndrome in 8 children (57%). Five children had both nephrotic and nephritic syndrome together (35%). Renal insufficiency was determined in 4 of 14 patients (28%). Surface antigen (HBsAg) was present in all, with no history of clinically apparent hepatitis. Investigation of all renal tissue samples with light and immunofluorescence microscopy confirmed the diagnosis of membranous glomerulonephritis (MGN) in 6, membranoproliferative glomerulonephritis (MPGN) in 7, and IgA nephropathy (IgAN) in 1 child. Renal tissue samples were studied by the immunoperoxidase method for HBsAg in all cases; only in 4 children was HBsAg detected in the glomeruli. Examination of liver tissue samples was available in 4 cases, revealing chronic hepatitis in all, with additional development of cirrhosis in 1 and the presence of HBsAg in hepatocytes in all. Of the patients, 8 received corticosteroid treatment; 1 of them achieved a complete remission, while 4 had a partial remission with persistent proteinuria and hematuria. Four patients who received no treatment had a spontaneous remission within 5 months to 10 years following the onset of the renal disease. Two patients died of renal failure, while 1 died of intercurrent sepsis. The patient with IgAN received interferon-alpha 2a and lamuvidine, which resulted in a remission and a marked decrease in HBV DNA titer. The remaining 2 were lost to follow-up. Although MGN has been reported as the nephropathy most commonly associated with HBsAg antigenemia in adults, our study revealed that MPGN could occur in children as well as MGN, without any clinical or historical evidence of hepatitis. The present study provides further evidence for a causal relationship between HBV hepatitis and HBs antigenemia-related glomerulonephritides in the pediatric age group. It also indicates the prognosis (71%) of the associated nephropathies with or without treatment is quite favorable in childhood.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children

Özdamar

Güçer

Tinaztepe

2003

Pediatric Nephrology

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“…These results suggested that a type-1 immune response was not predominant in idiopathic membranous nephropathy. In an analysis of PBMCs obtained from patients with hepatitis B virus (HBV) associated membranous nephropathy, IL-2 and IFN-γ production reportedly decreased more than that in HBV-infected patients without membranous nephropathy after in vitro stimulation with a hepatitis B core antigen [34]. Decreased IL-2 production may be a common phenomenon in membranous nephropathy.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with HBV-associated membranous nephropathy, increased IL-10 production after in vitro stimulation with a hepatitis B core antigen was also reported [34]. IL-10 is produced by Th2 clones [35], and it suppresses cytokine production by Th1 cells and NK cells [36].…”

Section: Discussionmentioning

confidence: 99%

Predominance of Type-2 Immune Response in Idiopathic Membranous Nephropathy

Hirayama

Ebihara²,

Yamamoto³

et al. 2002

Nephron

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Background: The Th1/Th2 paradigm is proving increasingly useful in the understanding of infectious diseases and many autoimmune diseases. Th1 cells predominantly produce interleukin-2 (IL-2) and interferon-γ (IFN-γ) and are instrumental in initiating delayed-type hypersensitivity and activating macrophages. Th2 cells secrete other cytokines, such as IL-4, IL-5, IL-10 and IL-13 that trigger B-cell activation and immunoglobulin synthesis. It has been shown that in patients with membranous nephropathy, there may be a predominance of Th2, because of the presence of IgG, particularly IgG4, which belongs to a subclass of the type-2 immune response, and complement deposits in glomeruli. In this study, we investigated the immunoresponse of helper T cells, i.e. Th predominance in patients with idiopathic membranous nephropathy. Methods: We used flow cytometry to assess the levels of circulating Th cells in patients with idiopathic membranous nephropathy (n = 8) and in normal individuals (n = 23) based on the expression of intracellular type-1 and type-2 cytokines. Because the production of each of these cytokines has a specific time course, we observed the cytokine synthesis at 3, 6, 9 and 12 h after stimulation. Results: The percentages of IL-2+/CD4+ cells from patients with idiopathic membranous nephropathy were significantly lower than those from normal individuals at 6, 9 and 12 h, with the difference becoming more significant over time. IFN-γ+/CD4+ cells and IL-4+/CD4+ cells were not significantly different between the two groups. In patients with idiopathic membranous nephropathy, the percentages of IL-10+/CD4+ cells were significantly higher than those in normal individuals at each point in time. Conclusion: Increased IL-10-producing Th cells may lead to suppression of delayed-type hypersensitivity and activate suppressor cells and IgG4 synthesis, resulting in idiopathic membranous nephropathy.

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“…A recent study by Lin et al [69]set out to elucidate why only some individuals with HBV infection developed MN. They did this by measuring serum HBeAg circulating immune complexes during the acute nephrotic phase of HBVMN and in the carrier stage of HBV.…”

Section: Pathogenesis Of Hbv-associated Nephropathymentioning

confidence: 99%

Hepatitis B Virus-Associated Nephropathy

Bhimma

Coovadia²

2004

Am J Nephrol

209

165

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A direct causal association between hepatitis B virus (HBV) infection and the development of nephropathy remains controversial. Epidemiological studies have shown that chronic carriage of HBV in some individuals (particularly children) leads to the development of nephrotic syndrome with a strong male predominance, the commonest histological type being membranous nephropathy (MN). Spontaneous clearance of HBV antigens (particularly the HBeAg) leads to abrogation of proteinuria. The isolation of immune complexes in the kidney suggests that the pathogenesis of the disease may have an immune-complex basis. Recent studies showing expression of HBV viral antigens in kidney tissue suggest direct viral-induced pathological alterations and chronic immunologic injury. Biosocial studies have detected no correlation between HBV carriage and proteinuria using both quantitative and qualitative urinary protein analysis. Genetic studies of HLA class I and II genes showed a predisposition to MN but no similar correlation in those with milder degrees of proteinuria. These findings suggest that milder proteinuria is unrelated to HBV carriage or genetic factors but the development of nephropathy, particularly MN, in patients with chronic HBV carriage (HBsAg and/or HBV DNA positive) is based on an interaction of virus and host factors. Although the natural history of the disease tends to remission with preservation of renal function, there is considerable morbidity and a small but significant mortality. Use of naturally occurring cytokines (such as interferon-α2b) and other candidate therapies accelerates clearance of the virus and proteinuria. The most effective tool in reducing the incidence of the disease is the use of HBV vaccines.

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Defect of Cell-Mediated Immune Response against Hepatitis B Virus; An Indication for Pathogenesis of Hepatitis-B-Virus-Associated Membranous Nephropathy

Cited by 21 publications

References 7 publications

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children

Hepatitis-B virus associated nephropathies: a clinicopathological study in 14 children

Predominance of Type-2 Immune Response in Idiopathic Membranous Nephropathy

Hepatitis B Virus-Associated Nephropathy

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