Deposition of hepatitis B e antigen in membranous glomerulonephritis: Identification by F(ab′)2 fragments of monoclonal antibody

209

165

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.

Section: Pathogenesis Of Hbv-associated Nephropathymentioning

confidence: 99%

Section: Clinical Presentation Of Hbvmnmentioning

confidence: 99%

Section: Pathogenesis Of Hbv-associated Nephropathymentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis B Virus-Associated Nephropathy

Bhimma

Coovadia²

2004

209

165

“…3]. Re cently, hepatitis Be antigen (HBeAg) has been found in glomerular immune deposits in membranous glomerulo nephritis of children, and the pathogenetic role of HBeAg in membranous glomerulonephritis has been em phasized [4][5][6]. It remains uncertain, however, whether HBsAg or HBeAg plays a pathogenetic role in the devel opment of membranoproliferative glomerulonephritis (MPGN) associated with HBV infection.…”

Section: Introductionmentioning

confidence: 99%

Membranoproliferative Glomerulonephritis Associated with Chronic Hepatitis B in Adults: Pathogenetic Role of HBsAg

Iida¹,

Izumino²,

Asaka³

et al. 1987

Two adult cases of membranoproliferative glomerulonephritis (MPGN) associated with chronic hepatitis B were reported. Serum HBsAg, HBeAg and anti-HBc were positive. Glomerular changes were essentially the same in both patients and consistent with MPGN type III. Immunofluorescence microscopy revealed diffuse granular and lumpy deposits of IgG, IgA, IgM, C1q and C3 along glomerular capillary walls and in mesangial areas. Granular deposition of HBsAg was observed along capillary walls and in mesangial areas, and the staining patterns were similar to those of immunoglobulins and complements in both patients. Glomerular deposition of HBeAg, however, was negative in one case, and only slight and segmental in the other case. These findings suggest that HBsAg rather than HBeAg may play a role in the pathogenesis of MPGN associated with hepatitis B virus infection in adults.

“…HBe antigen is known to combine with IgG, irrespective of antibody specificity [8]. On the other hand, it has been reported that HBe antigen is present in glomerular deposits of MGN, as demonstrated by fluoresceinated F(ab')2 fragments of monoclonal antibody raised against HBe antigen [9]. Therefore, the question as to whether the IgG de tected by immunofluorescent staining in the glomeruli of HBV-associated MGN is a specific anti-HBe antibody was not answered.…”

Section: Introductionmentioning

confidence: 99%

Presence of HBe Antibody in Glomerular Deposits in Membranous Glomerulonephritis Is Associated with Hepatitis B Virus Infection

Hattori

Furuse²,

Matsuda³

1988

The specificity of IgG on the glomerular capillary wall was investigated in 3 patients with hepatitis B virus associated membranous glomerulonephritis. The immune deposits on the capillary walls were stained by immunofluorescent antibody against HBe antigen and IgG. The eluted fluid (0.02 M citrate buffer, pH 3.2) from renal biopsy slices contained significant activity of HBe antibody, but not of HBs and HBe antibodies. After elution, the disappearance of IgG on the capillary walls was confirmed by immunofluorescence. Heterologous complement activation with fresh guinea pig complement was positive in the glomerular capillary walls from all 3 patients. Our observations support the notion that this disease is caused by HBe antigen-anti-HBe immune complexes.