ORIGINAL ARTICLE Clinical Significance of Anti-HEV IgA in Diagnosis of Acute Genotype 4 Hepatitis E Virus Infection Negative for Anti-HEV IgM Shujun Zhang Æ Deying Tian Æ Zhengang Zhang Æ Junhui Xiong Æ Quan Yuan Æ Shengxiang Ge Æ Jun Zhang Æ Ningshao Xia Received: 11 August 2008 / Accepted: 28 November 2008 / Published online: 1 January 2009 Ó Springer Science+Business Media, LLC 2008 Abstract Anti-HEV IgM is a diagnostic for recent or ongoing HEV infection. However, some patients with acute hepatitis E (AHE) negative for anti-HEV IgM in acute period were often observed in clinical practice. In this study, we constructed the anti-HEV IgA indirect ELISA assay to evaluate the significance of anti-HEV IgA. The specificity of anti-HEV IgA was 99.6%. Among 245 AHE patients, 84 samples from 84 patients were positive for HEV RNA. The positive rate of anti-HEV IgA, anti-HEV IgM and anti-HEV IgG in 84 samples positive for HEV RNA was 96.3, 97.6, and 88.1%, respectively, and no sample was negative for anti-HEV IgA and anti-HEV IgM simultaneously. Among 245 AHE patients, we found nine samples collected from nine patients in acute period were negative for anti-HEV IgM but positive for anti-HEV IgA and two samples were positive for HEV RNA. Detection of anti-HEV IgA can be a useful supplement for diagnosis of acute HEV infection especially in patients negative for anti-HEV IgM. Keywords Hepatitis E virus Á Acute hepatitis E Á Anti-HEV IgA Á Anti-HEV IgM Á Anti-HEV IgG Introduction Acute hepatitis E (AHE) is caused by hepatitis E virus (HEV) in developing countries where sanitation is subop- timal, however, epidemiological investigation indicated HEV infection also occurs among individuals in industri- alized countries with no history of travel to epidemic regions [1–3]. Like hepatitis A, it is transmitted by the fecal–oral route and contaminated water or food supplies have been implicated in major outbreaks. However, mor- tality rate of AHE is 0.5–4% in the general population and up to 20% among pregnant women [4]. The HEV genome is a single-stranded, positive-sense RNA, approximately 7.2 kb in length. It contains a short 5 0 untranslated region (UTR), three open reading frames (ORFs: ORF1, ORF2 and ORF3), and a short 3 0 UTR that is terminated by a poly(A) tract [5]. Although HEV sequences have been classified into four genotypes according to either the complete genome sequence or the nucleotide 80–450 of ORF1 [1, 6], only the single serotype was identified until now [4]. Genotype 1 is distributed in various developing countries in Asia and Africa; genotype 2 has been found in Mexico and Africa; genotype 3 is widely distributed and has been isolated from sporadic cases of an acute HEV infection and/or domestic pigs in the United States, several European countries, and Japan; genotype 4 is found mainly in Asian countries and contains strains from human and domestic pigs in China [7]. Clinical diagnosis of AHE is mainly done by a blood test that detects specific antibodies to HEV [8]. The immuno- globulin M (IgM) class of antibody against HEV (Anti- HEV IgM) is a diagnostic for recent or ongoing HEV infection for its short duration [9]. But the anti-HEV IgM alone should not be seen as evidence for infection because false-positive results are often caused by rheumatoid S. Zhang Á D. Tian (&) Á Z. Zhang Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan 430030, Hubei Province, China e-mail: deyingtian@163.com J. Xiong Á Q. Yuan Á S. Ge Á J. Zhang Á N. Xia National Institute of Diagnostics and Vaccine Development of Infectious Diseases, Xiamen University, Xiamen 361005, China 123 Dig Dis Sci (2009) 54:2512–2518 DOI 10.1007/s10620-008-0657-4