Diagnostic performance of selected commercial HEV IgM and IgG ELISAs for immunocompromised and immunocompetent patients
Section snippets
Background
Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus that causes sub-clinical, acute and chronic infections, characterised by hepatitis, though extra-hepatic manifestations have been described. Four genotypes are known to infect humans (genotype 1–4), the epidemiology and geographical distribution of which differs between genotypes 1–2 and 3–4. HEV genotype 3 and, to lesser extent, genotype 4 is recognised as an emerging pathogen in industrialised countries [1], [2] and it can
Objectives
We first aimed to evaluate the analytical and diagnostic performance of selected commercially available IgM and IgG ELISAs for the detection of both genotype 1 and 3 HEV infections using a well-defined serum panel of polymerase chain reaction (PCR)-confirmed HEV infected patients. Second, we targeted investigation of the HEV antibody responses in immunocompetent and immunocompromised patients.
Sample collection
The samples used in our retrospective study had been collected in the time period 2003–2011 during hospitalisation and routine visits by patients to our outpatient clinic for clinical assessments. Serum/ethylenediaminetetraacetic acid (EDTA)–plasma samples have been stored at −20 °C and −80 °C, respectively.
Sensitivity panel
In order to assess the analytical sensitivity we performed a twofold end-point titration of a genotype 1 and 3 HEV IgM and IgG antibody-positive serum, starting from 1/125 and 1/25,
Analytical sensitivity
IgM limiting dilutions indicated that the highest analytical sensitivity among the IgM ELISAs for genotype 1 was achieved by MP Diagnostics and Wantai assays. For genotype 3 IgM antibody titration, the Wantai assay was the most sensitive assay (Table 2). Remarkably, a wide variety of s/co ratios was observed, among which the IgM and IgG Wantai assay stood out (s/co ratios of 18 as upper limit of detection). IgG limiting dilutions indicated that the highest analytical sensitivity in head-to-head
Discussion
Autochthonous HEV infection, caused by genotype 3, is recognised as an emerging infectious disease in industrialised countries. Only limited data are available on the diagnostic performance of commercial IgM and IgG ELISAs or combination of these two, and the sensitivity of ELISAs coated with genotype 1 and 2 antigens is questioned for the detection of genotypes 3 and 4. Our study gives more insight into the diagnostic performance and antibody kinetics of commercial anti-HEV IgM and IgG assays
Funding
This work was supported by the Virgo consortium, funded by the Dutch Government (FES0908), by The Netherlands Genomics Initiative (NGI) (project number 050-060-452) and by the European Community Seventh Framework Programme (FP7/2007-2013) under project EMPERIE (Grant agreement No. 223498).
Conflicts of interest
S.D.P received travelling and accommodation expenses from Mikrogen. A.D.M.E.O. is chief science officer of Viroclinics Biosciences BV, a spin-out Erasmus MC contract research organisation that collaborates with pharmaceutical companies. The other authors have no conflicts of interest to disclose.
Ethical approval
This study was approved by the hospital medical ethical committee (MEC-2011-277).
Acknowledgements
We thank Claudia Mulders and Sandra Scherbeijn for technical assistance, Hans Kruining for his help with LIMS database searches and Jean-Luc Murk for his expert opinion. We thank Mikrogen and MP Products for providing the new IgM recomwell HEV ELISA and Diacheck anti IgM and IgG HEV ELISA.
References (21)
- et al.
an emerging infection in developed countries
Lancet Infect Dis
(2008) - et al.
Clinical implications of chronic hepatitis E virus infection in heart transplant recipients
J Heart Lung Transplant Off Pub Int Soc Heart Transplant
(2013) - et al.
Low risk of hepatitis E virus reactivation after haematopoietic stem cell transplantation
J Clin Virol
(2012) - et al.
Report of a collaborative study to assess the suitability of a reference reagent for antibodies to hepatitis E virus
Biol J Int Assoc Biol Standard
(2002) - et al.
Serological diagnostics of hepatitis E virus infection
Virus Res
(2011) - et al.
Epidemiology of hepatitis E: current status
J Gastroenterol Hepatol
(2009) - et al.
Profile of acute infectious markers in sporadic hepatitis E
PLoS One
(2010) - et al.
Characteristics of autochthonous hepatitis E virus infection in solid-organ transplant recipients in France
J Infect Dis
(2010) - et al.
Hepatitis E virus infection among solid organ transplant recipients, the Netherlands
Emerg Infect Dis
(2012) - et al.
A comparison of two commercially available anti-HEV IgG kits and a re-evaluation of anti-HEV IgG seroprevalence data in developed countries
J Med Virol
(2010)