TY - JOUR
T1 - Microsphere-based IgM and IgG avidity assays for human parvovirus B19, human cytomegalovirus, and toxoplasma gondii
AU - Wang, Yilin
AU - Hedman, Lea
AU - Nurmi, Visa
AU - Ziemele, Inga
AU - Perdomo, Maria F.
AU - Söderlund-Venermo, Maria
AU - Hedman, Klaus
N1 - Funding Information:
We thank the Helsinki University Hospital Research & Education and Research & Development funds, the Sigrid Jus?lius Foundation, the Medical Society of Finland (FLS), the Finnish Society of Sciences and Letters, Finnish Medical Foundation, and the Instrumentarium Research Fund. We are grateful to Piia Karisola at the University of Helsinki and Maija Lappalainen at HUSLAB for permission to use the Bioplex devices. Y.W., M.S.-V., M.F.P., and K.H. contributed to the conception and design of this study. Y.W. carried out the development of SIAs, experiments, and acquisition and analysis of data and drafted the manuscript. V.N., M.F.P., and I.Z. participated in the development of IgG avidity SIAs. L.H. carried out B19 EIAs and collected data from HCMV and T. gondii Vidas and Architect assays. M.S.-V., M.F.P., and K.H. helped to revise the manuscript. All authors read and approved the final manuscript.
Publisher Copyright:
© 2020 Wang et al.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3/18
Y1 - 2020/3/18
N2 - Human parvovirus B19 (here B19), human cytomegalovirus (HCMV), and Toxoplasma gondii infections during pregnancy can lead to severe complications. While traditional diagnosis of infections is mostly confined to one pathogen at a time, a multiplex array is a feasible alternative to improve diagnostic management and costefficiency. In the present study, for these three pathogens, we developed microspherebased suspension immunoassays (SIAs) in multiplex and monoplex formats for the detection of antimicrobial IgM antibodies as well as corresponding chaotrope-based IgG avidity SIAs. We determined the diagnostic performances of the SIAs versus in-house and commercial reference assays using a panel of 318 serum samples from wellcharacterized clinical cohorts. All the newly developed assays exhibited excellent performance compared to the corresponding high-quality reference methods. The positive and negative percent agreements of the IgM SIAs in comparison with reference methods were 95 to 100% and 98 to 100%, and those of the IgG avidity SIAs were 92 to 100% and 95 to 100%, respectively. Kappa efficiency values between the SIAs and the corresponding reference assays were 0.91 to 1. Furthermore, with another panel comprising 391 clinical samples from individuals with primary infection by B19, HCMV, or T. gondii, the IgM SIAs were highly sensitive for the detection of acute infections, and the IgG avidity SIAs were highly specific for the separation of primary infections from past immunity. Altogether, the strategy of IgM multiplex screening followed by IgG avidity reflex testing can provide high-throughput and accurate means for the detection and stage determination of B19, HCMV, and T. gondii infections. IMPORTANCE Human parvovirus B19, human cytomegalovirus, and Toxoplasma gondii are ubiquitous pathogens. Their infections are often asymptomatic or mild in the general population yet may be transmitted from mother to fetus during pregnancy. Maternal infections by these pathogens can cause severe complications to the fetus or congenital abnormalities. As a rule, the risk of maternal transmission is critically related to the infection time; hence, it is important to determine when a pregnant woman has acquired the infection. In this study, we developed new diagnostic approaches for the timing of infections by three pathogens. All the new assays appeared to be highly sensitive and specific, providing powerful tools for medical diagnosis.
AB - Human parvovirus B19 (here B19), human cytomegalovirus (HCMV), and Toxoplasma gondii infections during pregnancy can lead to severe complications. While traditional diagnosis of infections is mostly confined to one pathogen at a time, a multiplex array is a feasible alternative to improve diagnostic management and costefficiency. In the present study, for these three pathogens, we developed microspherebased suspension immunoassays (SIAs) in multiplex and monoplex formats for the detection of antimicrobial IgM antibodies as well as corresponding chaotrope-based IgG avidity SIAs. We determined the diagnostic performances of the SIAs versus in-house and commercial reference assays using a panel of 318 serum samples from wellcharacterized clinical cohorts. All the newly developed assays exhibited excellent performance compared to the corresponding high-quality reference methods. The positive and negative percent agreements of the IgM SIAs in comparison with reference methods were 95 to 100% and 98 to 100%, and those of the IgG avidity SIAs were 92 to 100% and 95 to 100%, respectively. Kappa efficiency values between the SIAs and the corresponding reference assays were 0.91 to 1. Furthermore, with another panel comprising 391 clinical samples from individuals with primary infection by B19, HCMV, or T. gondii, the IgM SIAs were highly sensitive for the detection of acute infections, and the IgG avidity SIAs were highly specific for the separation of primary infections from past immunity. Altogether, the strategy of IgM multiplex screening followed by IgG avidity reflex testing can provide high-throughput and accurate means for the detection and stage determination of B19, HCMV, and T. gondii infections. IMPORTANCE Human parvovirus B19, human cytomegalovirus, and Toxoplasma gondii are ubiquitous pathogens. Their infections are often asymptomatic or mild in the general population yet may be transmitted from mother to fetus during pregnancy. Maternal infections by these pathogens can cause severe complications to the fetus or congenital abnormalities. As a rule, the risk of maternal transmission is critically related to the infection time; hence, it is important to determine when a pregnant woman has acquired the infection. In this study, we developed new diagnostic approaches for the timing of infections by three pathogens. All the new assays appeared to be highly sensitive and specific, providing powerful tools for medical diagnosis.
KW - B19
KW - HCMV
KW - IgG avidity
KW - IgM
KW - Infection time
KW - Intrauterine infection
KW - Multiplex
KW - Suspension immunoassay
KW - T. gondii
UR - https://www.mendeley.com/catalogue/a80768e9-d84e-33a8-90fb-984476e138d1/
U2 - 10.1128/msphere.00905-19
DO - 10.1128/msphere.00905-19
M3 - Article
C2 - 32188754
AN - SCOPUS:85082066688
SN - 2379-5042
VL - 5
JO - mSphere
JF - mSphere
IS - 2
M1 - e00905-19
ER -