Key result
Urine HEV ORF2 antigen levels were concentrated >10-fold compared to serum, yielding higher diagnostic sensitivity and appearing 6 days earlier than viremia in animal models.
Why the study?
Urinary shedding of HEV antigen has gained interest, but its origin, antigenicity, diagnostic performance, and diagnostic significance remained to be uncovered.
Does urine HEV ORF2 antigen provide higher diagnostic sensitivity and earlier detection compared to serum antigen in HEV infection?
Observational
Does urine HEV ORF2 antigen provide higher diagnostic sensitivity and earlier detection compared to serum antigen in HEV infection?
Urine HEV ORF2 antigen offers higher diagnostic sensitivity and a wider detection window than serum antigen for hepatitis E infection.
Urine HEV antigen may enable earlier, more sensitive detection; leaves open clinical translation pending human studies.
BACKGROUND AND AIMS: HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection. APPROACH AND RESULTS: Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s-like dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2 S ) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model. CONCLUSIONS: Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.
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Dong et al. (2022) conducted an observational in Acute and chronic HEV infection. Urine HEV ORF2 antigen testing vs. Serum HEV ORF2 antigen testing was evaluated on Diagnostic sensitivity and antigen levels. Urine HEV ORF2 antigen levels were concentrated >10-fold compared to serum, yielding higher diagnostic sensitivity and appearing 6 days earlier than viremia in animal models.
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