Comparison of class and subclass distribution of antibodies to the hepatitis B core and B e antigens in chronic hepatitis B

The IgG subclasses IgM and IgA1 of antibodies to hepatitis B core antigen (anti‐HBc) and hepatitis B e antigen (anti‐HBe) were assayed in sera from 82 patients with chronic hepatitis B utilising class/subclass‐specific enzyme immunoassays (EIA). The solid‐phase was either recombinant hepatitis B core antigen (rHBcAg) or rHBcAg converted to HBeAg by addition of 0.1% SDS with remaining HBcAg antigenicity blocked with monoclonal anti‐HBc. Anti‐HBc IgG1 was detected in 81 sera at a geometrical mean titre (GMT) of 296, 110  ÷× 2.9. Anti‐HBc IgG2 was not detected in any of the sera, and anti‐HBc IgG3 and IgG4 were detected in 50 and 37 sera, respectively. Anti‐HBc IgM and IgA1 were both significantly correlated to the presence of HBV DNA. The predominant antibody to HBeAg was found to be IgG1, being detected in 45 sera with a GMT of 1,035  ÷× 3.3. Anti‐HBe IgG2 was not detected in any serum, while anti‐HBe IgG3 and IgG4 were found in 8 and 23 sera, respectively. Anti‐HBe IgG1, IgG3, and IgG4 were mainly detected in sera positive for anti‐HBe in RIA (Abbott). No patient was found positive for anti‐HBe IgA1 or IgM. Thus, in contrast to HBcAg, HBeAg does not trigger a persistent IgM and IgA1 response in chronic hepatitis B. The levels of anti‐HBe IgG1 and IgG3 were much lower than the levels of anti‐HBc IgG1 and IgG3. The presence of anti‐HBe IgG4 was significantly correlated to that of anti‐HBc IgG4. The relative levels of anti‐HBc IgG subclasses were found to be IgG1 > IgG3 > IgG4, whereas the relative levels of anti‐HBe subclasses were IgG1 ≥ IgG4 ≥ IgG3. The anti‐HBe IgG1:IgG4 ratio was much lower than that of anti‐HBc, 2.7:1 versus 890:1. Our findings support the suggestion of differences at the B‐cell level in the regulation of the immunoresponse to HBeAg and HBcAg, though both antigenic epitopes reside on the same polypeptide.