Diagnostic relevance of immunoglobulin G avidity for hepatitis A virus

Abstract

Diagnosis of acute hepatitis A virus (HAV) infection is based on the detection of HAV immunoglobulin M (IgM). However, IgM could be detected due to nonspecific polyclonal activation of the immune system. An avidity test for anti-HAV IgG was developed to distinguish acute infection, where low-avidity antibodies are detected, from immune reactivation. The assay was tested on 104 samples, including 11 sera from patients with past infection, 15 sera from patients with acute infection and 4 collected after recovery, 10 sera from vaccinated subjects, 4 sera from patients with suspected immune reactivation, and 60 unselected HAV-IgM positive sera, collected over 1 year in a routine laboratory. The avidity index (AI) was expressed as percentage. The results were provided as the mean +/- one standard deviation. Patients with a history of prior infection had AIs of >70% (mean, 86% +/- 10), whereas the mean AI was 36% +/- 16 during acute HAV infection (P < 0.001). Within the first month after the onset of hepatitis, avidity was either noncalculable due to a very low IgG titer or <50%. In patients with immune reactivation, avidity was >70% (88% +/- 10%), a finding consistent with a prior infection. Among the 60 unselected sera, 35 (58%) had a noncalculable or <50% avidity, and most of them had a detectable HAV RNA, confirming HAV infection. In contrast, 16 (27%) had an avidity of >70%, and none was reverse transcription-PCR positive, suggesting immune reactivation. These 16 patients were significantly older than the others (50 +/- 16 years versus 26 +/- 14 years). The new anti-HAV IgG avidity assay we developed could improve HAV infection diagnosis, particularly in elderly patients.

FIG. 1.

AI values for 11 patients with acute infections according to the date of symptom onset. The evolution over time is indicated for three patients.

FIG. 2.

IgG anti-HAV AI according to clinical data.