The suggestion that hepatitis B virus (HBV) may be involved in a pathologic process leading to the development of chronic glomerulonephritis is derived from the clinical and immunological similarities of the HBV infection to serum sickness. Since the first report¹⁾ of the association between HBV and membranous nephropathy, there have been several other reports^2–16) strongly suggesting that HBV, through an immune response elicited by one of its antigens, is causally related to the development of glomerular changes in humans.

On renal biopsy the lesion was variable including MGN^{1,4,7,8,19–21)}, MPGN^3,4,15), Mesangioproliferative GN^5,9,13), and IgA GN^20–22), but the exact pathogenic mechanism by which certain individuals with chronic HBV infection develop glomerulonephritis is unknown. In spite of so many papers^{4,7,10,12,13,19,20,22)} demonstrating HBsAg in the glomerular capillary wall, HBsAg has been considered unlikely to deposit subepithelial space because of its large size (>10⁶ dalton) and anionic charge²³⁾, but it may be deposited by a trapping mechanism in the mesangial and subendothelial area regardless of its size and charge²³⁾. In our preliminary study, HBsAg/IgG was positive in HBsAg positive serum of 74.3% of the B viral liver disease group and 10% of the healthy control group. The presence of HBsAg/IgG CX reflects the presence of anti HBs in circulation even if this were not detected by a conventional assay system for anti HBs. So, the quantitative measurement of the HBsAg/IgG CX may reflect the characteristics and nature of anti HBs in each case.

In this regard, it is interesting how the prevalence rate and amount of HBsAg/IgG CX will be found in the HBsAg positive serum of MGN and MPGN patients.

Even though recent evidence suggests that, with few exceptions, circulating immune complex measurements do not correlate with disease activity²⁵⁾, from the background of serum sickness animal models^26,27), it has been accepted that continuous formation of the immune complex is necessary to maintain the chronicity of GN.

The methods commonly used to gather the evidence that supports of the theory of HBV as a primary cause of immune complex GN were the detection of HBsAg in glomerular basement membrane in association with immune globulin and the detection of free form and/or complexed form of the HBAg and anti HBs in circulation.

Experimental studies²⁸⁾ in rats indicate that complexes with a molecular mass of 1,000,000 daltons or less precipitate in the glomerular basement membrane and subepithelial space to induce typical MGN. The 20 nm spherical HBAg particles, the most commonly demonstrated antigen, have a molecular mass of 3,000,000 daltons even without antibody²⁸⁾.

In this regard, in spite of so many papers showing HBsAg deposited in the basement membrane, HBsAg seems impossible to pass through the size barrier of the basement membrane. Anyway, an immune complex containing small-sized HBsAg molecular fragments, but with the same immunoreactivity, may be responsible for the lesion²⁸⁾.

The renal lesions that have been presented in literature^6,12–14) appear to span nearly the whole spectrum of renal pathology, although the MGN and MPGN have been more common. As far as the accumulated knowledge about the HBsAg/antiHBs CX in pathologic process of glomerulonephritis is concerned, MGN may be due to an in situ HBsAg/antiHBs CX formation in the subepithelial space, and MPGN may be due to a trapping process of circulating HBsAg/anti HBs CX in the subendothelial space and mesangium.

The exact incidence of HBV-associated GN is not known, but several reports^5,12–14) suggest that, from cases of GN with immunofluorescent evidence of an immune complex lesion, HBsAg was positive in as many as 16.3–56.2% of cases.

Glomerular lesions could be influenced by various factors including quantitiy and size of the complexes as well as by genetically-determined differences in individual host responsiveness²⁹⁾.

If HBsAg is a primary cause of immune complex glomerulonephritis, the nature and characteristics of anti HBs, including avidity and/or affinity, the amount, isotype, and idotype of anti HBs should be the key of pathogenesis. Of course, the nature and characteristics of HBsAg/IgG CX should be influenced not only by the nature of anti HBs but also by the nature and amount of HBsAg. HBsAg may accumulate levels as high as 10¹⁴ particles or 200 μg/ml in the blood of HBV-infected individuals³⁰⁾, and it will vary depending on the clinical situation. But in a chronic state of HBV infection, the concentration of HBsAg will be stable, and considering that more than 80% of the particle surface area can still be exposed even after saturation with anti HBs³¹⁾, the HBsAg surface area is not limiting the amount of antibody that can bind, the nature of anti HBs is a more important factor in HBsAg/IgG CX formation. In the liver diseases group, the range of HBsAg/IgG CX was wide, ranging from 62 ng/ml to 4466 ng/ml. Theoretically, HBsAg/IgG CX within these ranges might include various degrees of affinity and variable kinds of antibody class. The incidence of HBsAg/IgG CX was high in the B-virus related liver diseases group (57–100%), but it was 10% in the healthy carrier group and 14.3% in the MGN group and 12.5% in the MPGN group. The mass of HBsAg/IgG CX was large and variable in the liver diseases group but similar in the healthy carrier group (41±2.6ng/ml, n=5) and in the MGN (50 ng/ml) and MPGN (42 ng/ml) groups.

With the finding that in the liver disease group, no one suffered from glomerulopathy even with various kinds of anti HBs, our result showed that the characteristics of antibody formed against HBsAg are similar to those between the healthy carrier group and the MGN and MPGN group. Circulating HBsAg and it’s antibody seems to be non causative of MGN and MPGN in HBsAg positive individuals.