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Journal of Clinical Microbiology, January 2005, p. 49-56, Vol. 43, No. 1
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.1.49-56.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Simultaneous Detection of Immunoglobulin A (IgA) and IgM Antibodies against Hepatitis E Virus (HEV) Is Highly Specific for Diagnosis of Acute HEV Infection

Masaharu Takahashi,1 Shigeyuki Kusakai,2 Hitoshi Mizuo,3 Kazuyuki Suzuki,4 Kuniko Fujimura,5 Kazuo Masuko,6 Yoshiki Sugai,7 Tatsuya Aikawa,8 Tsutomu Nishizawa,1 and Hiroaki Okamoto1*

Division of Virology, Department of Infection and Immunity, Jichi Medical School, Tochigi-Ken,1 Institute of Immunology, Tokyo,2 Department of Internal Medicine, Kin-ikyo Chuo Hospital, Hokkaido,3 First Department of Internal Medicine, Iwate Medical University, Iwate-Ken,4 Japanese Red Cross Yamaguchi Blood Center, Yamaguchi-Ken,5 Masuko Memorial Hospital and Masuko Institute for Medical Research, Aichi-Ken,6 Department of Internal Medicine, Iwaki Kyoritsu General Hospital, Fukushima-Ken,7 Aikawa Internal Medicine Hospital, Ibaraki-Ken, Japan8

Received 3 July 2004/ Returned for modification 21 September 2004/ Accepted 29 September 2004

Serum samples collected from 68 patients (age, mean ± the standard deviation [SD], 56.3 ± 12.8 years) at admission who were subsequently molecularly diagnosed as having hepatitis E and from 2,781 individuals who were assumed not to have been recently infected with hepatitis E virus (HEV; negative controls; 52.9 ± 18.9 years), were tested for immunoglobulin M (IgM) and IgA classes of antibodies to HEV (anti-HEV) by in-house solid-phase enzyme immunoassay with recombinant open reading frame 2 protein expressed in the pupae of silkworm as the antigen probe. The 68 patients with hepatitis E had both anti-HEV IgM and anti-HEV IgA. Among the 2,781 controls, 16 (0.6%) had anti-HEV IgM alone and 4 (0.1%) had anti-HEV IgA alone: these IgA/IgM anti-HEV-positive individuals were not only negative for HEV RNA but lack IgG anti-HEV antibody as well (at least in most of the cases). Periodic serum samples obtained from 15 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, and anti-HEV IgA. Although HEV RNA was detectable in the serum until 7 to 40 (21.4 ± 9.7) days after disease onset, both IgM and IgA anti-HEV antibodies were detectable until 37, 55, or 62 days after disease onset in three patients and up through the end of the observation period (50 to 144 days) in 12 patients. These results indicate that detection of anti-HEV IgA alone or along with anti-HEV IgM is useful for serological diagnosis of hepatitis E with increased specificity and longer duration of positivity than that by RNA detection.

* Corresponding author. Mailing address: Division of Virology, Department of Infection and Immunity, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-Machi, Tochigi-Ken 329-0498, Japan. Phone: 81-285-58-7404. Fax: 81-285-44-1557. E-mail: hokamoto{at}jichi.ac.jp.

Journal of Clinical Microbiology, January 2005, p. 49-56, Vol. 43, No. 1
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.1.49-56.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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