Detection of hepatitis E virus-specific immunoglobulin a in patients infected with hepatitis E virus genotype 1 or 3

Abstract

Currently, diagnosis of acute hepatitis E virus (HEV) in patients is primarily based on anti-HEV immunoglobulin M (IgM) detection. However, several investigations suggest the use of HEV-specific IgA for diagnosing acute HEV infections. We evaluated two commercially available assays, an IgA enzyme-linked immunosorbent assay (ELISA) (Diacheck) and an adapted immunoblot protocol (Mikrogen) for IgA detection and compared the performance in genotype 1- and 3-infected patients. The specificity of the IgA assays was high, with no positive reactions in a control group of 18 acute hepatitis patients who were negative for HEV. The sensitivity calculated in nine PCR-positive type 1-infected patients was 100% in both assays but was clearly lower in genotype 3-infected patients (n = 14), with sensitivities of only 67% and 57% for the ELISA and immunoblot assay, respectively. The lower IgA responses detected in genotype 3-infected patients could be caused by the use of only the genotype 1 and 2 antigens in the serological assays. Interestingly in two patients with possible infection through blood transfusion no response or intermediate IgA responses were detected, and this might confirm the parenteral route of transmission. In both the type 1- and type 3-infected patients both the IgA and IgM responses disappeared simultaneously. We conclude that IgA detection is of limited value for the serodiagnosis of acute HEV cases, particularly with genotype 3.

FIG. 1.

HEV-specific IgA antibodies measured by ELISA in controls and in hepatitis patients. Serum samples were from controls (n = 18), 8 type 1-infected PCR-positive patients (9 samples), 9 type 3-infected PCR-positive patients, 5 type 1 and 3 type 3 follow-up samples from serologically confirmed HEV patients based on a positive IgM and IgG response or PCR-positive result in a previous sample, 20 patients with an IgG response in the immunoblot assay (score of 4 to 12) in the absence of an IgM response, and sera from 6 hepatitis patient with an IgM response only.

FIG. 2.

HEV-specific IgA antibodies measured by immunoblot assay in controls and in hepatitis patients. Serum samples were from controls (n = 17), 9 type 1-infected PCR-positive patients (10 samples), 14 type 3-infected PCR-positive patients (15 samples), 5 type 1 and 8 (9 samples) follow-up samples from serologically confirmed HEV patients based on a positive IgM and IgG response or PCR positive result in a previous sample, 20 patients with IgG response in the immunoblot assay (score of 4 to 12) in the absence of an IgM response, and sera from 6 hepatitis patient with an IgM response only.