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Clinical and Epidemiological Relevance of Quantitating Hepatitis E Virus-Specific Immunoglobulin M

Jitvimol Seriwatana,¹ Mrigendra P. Shrestha,² Robert M. Scott,² Sergei A. Tsarev,^1, David W. Vaughn,^3, Khin Saw Aye Myint,³ and Bruce L. Innis^1*

Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, Maryland 20910,¹ Walter Reed/Armed Forces Research Institute of Medical Sciences Research Unit—Nepal, Kathmandu, Nepal,² Department of Virology, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand³

Received 4 March 2002/ Returned for modification 2 April 2002/ Accepted 1 June 2002

Diagnosis of acute hepatitis E by detection of hepatitis E virus (HEV)-specific immunoglobulin M (IgM) is an established procedure. We investigated whether quantitation of HEV IgM and its ratio to HEV total Ig furnished more information than conventional IgM tests that are interpreted as positive or negative. A previously described indirect immunoassay for total Ig against a baculovirus-expressed HEV capsid protein was modified to quantitate HEV-specific IgM in Walter Reed (WR) antibody units by using a reference antiserum and the four-parameter logistic model. A receiver-operating characteristics curve derived from 197 true-positive specimens and 449 true-negative specimens identified 30 WR units/ml as an optimum cut point. The median HEV IgM level in 36 patients with acute hepatitis E fell from 3,000 to 100 WR units/ml over 6 months, suggesting that 100 WR units/ml would be a more appropriate cut point for distinguishing recent from remote IgM responses. Among three hepatitis E case series, determination of the HEV IgM-to-total-Ig ratio in acute-phase serum revealed that most patients had high ratios consistent with primary infections whereas a few had low ratios, suggesting that they had sustained reinfections that elicited anamnestic antibody responses. The diagnostic utility of the new IgM test was similar to that of a commercially available test that uses different HEV antigens. In conclusion, we found that HEV IgM can be detected specifically in >95% of acute hepatitis E cases defined by detection of the virus genome in serum and that quantitation of HEV IgM and its ratio to total Ig provides insight into infection timing and prior immunity.

Present address: Science Applications International Corporation, New Media Systems Division, Reston, VA 20190.

Present address: Department of Virus Diseases, Walter Reed Army Institute of Research, Silver Spring, MD 20910.

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