Enzyme immunoassay for anti-hepatitis B core (HBc) immunoglobulin G1 and significance of low-level results in competitive assays for anti-HBc

Abstract

An enzyme immunoassay (EIA) for anti-hepatitis B core (HBc) immunoglobulin Gi (IgGl) was compared with a commercial radioimmunoassay (RIA) for anti-HBc antibody (Corab; Abbott Laboratories, North Chicago, 111.). In parallel tests of 445 consecutive samples, discrepant results were obtained with 2 samples, 1 of which was positive only by the RIA and the other of which was positive only by the EIA for anti-HBc IgG1. In tests of another 192 samples with low blocking activity in the RIA (inhibition range, 90 to 30%), 10 samples gave discrepant results, 5 of which were positive only by the RIA and the other 5 of which were positive only by the EIA for anti-HBc IgGl. Of 12 samples with discrepant results, 11 samples were tested further for anti-HBc IgG3, IgM, and IgAl by the EIA. Of these, seven samples were positive for anti-HBc IgGl, anti-HBc IgG3, or both. All seven samples were also positive for anti-hepatitis B surface (HBs) antigen. Three samples were negative for anti-HBc IgGl, anti-HBc IgG3, or both but were positive for anti-HBc IgM, anti-HBc IgAl, or both; and one sample was reactive only in the RIA. These four samples were all negative for anti-HBs. Thus, low-level results in the RIA caused by anti-HBc IgM, anti-HBc IgA, or both reflect the unspecific activation of immature B lymphocytes that is not related to previous exposure to hepatitis B virus (HBV). In contrast, the presence of anti-HBc IgGl, anti-HBc IgG3, or both indicates differentiated anti-HBc IgG-producing plasma cells and previous exposure to HBV, as was also shown by the presence of anti-HBs. On class and subclass determination for confirmation of positivity for anti-HBc in 19 serum samples, which was identified by screening of blood from 1,343 donors by a competitive EIA (Hepanostika; Organon), 9 samples with positive results, all low level, did not indicate previous exposure to HBV. It was concluded that determination of classes and subclasses of anti-HBc provides a tool for discriminating positive anti-HBc results not caused by HBV exposure.

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

“…However, high titres of anti-HBc IgM and IgAl were also found, though less frequently, in HBV DNA-negative sera. IgGl was found to be the dominant immunoglobulin among the antibody classes and subclasses of anti-HBc, in agreement with previous findings [Sallberg et al, 1988;Sallberg and Magnius, 1989 I. Anti-HBc IgGl generally occurs in high titres (>10,000) in chronic HBV infection. The other IgG subclasses of anti-HBc IgG3 and IgG4 occur less frequently and also at lower titres.…”

The Isolated Anti-HBc Reactivity: New Developments/Die Bedeutung des isoliert anti-HBc positiven Befundes: neue Aspekte

“…Isolated false-positive anti-HBc reactivity (presence of anti-HBc; HBsAg and anti-HBs negative) has been attributed to cross-reactive antibodies or interfering substances in serum; this effect was also observed for anti-HBs [2,3]. One of the major reasons for false-positive reactivity is the non-specific activation of premature Blymphocytes resulting in the production of IgA-or IgM-related molecules without previous exposure to HBV [6,7]. Pre-treatment of serum samples with reducing agents, i. e. dithiothreitol (DTT) or potassium bisulphite (MBS) significantly improves the specificity of the anti-HBc determination [8,9].…”

“…Generally, strong signals are reproducible over years, whereas weak reactivities are not. Alternative data from selected populations indicate that samples with very low levels of reductant-stable anti-HBc activity are associated with anti-HBs and are presumably true anti-HBc-IgG positive [7,13]. This suggests that the sensitivity of anti-HBc assays should be increased in order to detect true low-level reactive samples.…”

The validity of injecting drug users' self‐reports about sexually transmitted diseases: a comparison of survey and serological data

“…However, manufacturers of different enzyme immunoassay tests like Corzyme provide different specifications for distinguishing between an anti-HBc positive serum and an anti-HBc negative serum, making it difficult to determine consistently whether certain results should be categorized as positive or negative (Caspari et al, 1989). Furthermore, specificity of low-level results obtained by enzyme immunoassays is a recognized problem for those engaged in the laboratory diagnosis of hepatitis B (Sallberg & Magnius, 1989). On repeated testing, individuals with initially low positive responses tend to become negative over time (Hadler et al, 1984).…”