Whole Blood Based Cytokine Release Assay Assesses Cellular Immunity in Hepatitis E Resolver Patients

BACKGROUND:Hepatitis E virus (HEV) infection is being recognized as a major concern in developed as well as industrialized countries, especially for immunocompromised patients at risk of developing chronic hepatitis E. OBJECTIVE:We developed an HEV specific interferon gamma release assay (IGRA) for assessing T cell responsiveness to HEV antigens in resolved hepatitis E patients (RHE). METHODS:8 RHE patients and 13 HEV seronegative healthy controls (HC) were tested for IFNγ- and IL2-secretion in whole blood after challenge with recombinant HEV ORF2 genotype 1 and ORF2 genotype 3 antigens. RESULTS:The developed IGRA test differentiated by trend between the RHE group and HEV seronegative HC. RHE patients showed a stronger IL2 response to ORF2 genotype 1 or genotype 3 (180±47 and 171±39 pg/ml) compared to HC (96±34 pg/ml and 65±20 pg/ml). IFNγ responses were negligible. CONCLUSIONS:HEV specific IGRAs using IL2 as a marker should help to further clarify prior exposure to HEV.