Identification of ADA as a Biomarker for Atypical Epstein Barr Virus
                    Infection in Children

Ting Shi; Linlin Huang; Wangsheng Zhang; Wenxin Shi; Jiahui Wu; Yuanxi Bian; Yanqun Jiang; Jianmei Tian

doi:10.1055/a-2041-2986

Klinische Pädiatrie, Table of Contents

Klin Padiatr 2023; 235(04): 221-227
DOI: 10.1055/a-2041-2986

Original Article

Identification of ADA as a Biomarker for Atypical Epstein Barr Virus Infection in Children

Authors

Ting Shi

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China
Linlin Huang

²Pediatric Intensive Care Unit, Soochow University Affiliated Children’s Hospital, Suzhou, China
Wangsheng Zhang

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China
Wenxin Shi

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China
Jiahui Wu

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China
Yuanxi Bian

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China
Yanqun Jiang

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China
Jianmei Tian

¹Department of Infectious Diseases, Soochow University Affiliated Children’s Hospital, Suzhou, China

Abstract

Objective This study aims to explore the ability of adenosine deaminase (ADA) to discriminate atypical Epstein Barr virus (EBV) infection in children from acute febrile illness.

Methods All children admitted to the Children’s Hospital of Soochow University between 2018 and 2019, who were acute febrile patients and subjected to the plasma EBV-DNA polymerase chain reaction (PCR) and indirect immunofluorescence (IIF) assay for EBV-specific antibodies assays. The diagnostic value of each detection index was compared by the area under the ROC curve.

Results In children with atypical Epstein Barr virus infection, the sensitivity, specificity, positive predictive value, negative predictive value and Youden index were 62.87%, 100.00%,100.00%, 61.73% and 0.63 for EBV-DNA PCR assay, 80.84%, 100.00%, 100.00%, 75.76% and 0.81 for VCA-IgG avidity and 89.22%, 87.00%, 91.98%, 82.86% and 0.76 for ADA. VCA-IgG avidity (AUC=0.904, P<0.01) and ADA (AUC=0.881, P<0.01) assays had the great diagnostic efficiency. In addition, the sensitivity, specificity and AUC were 92.75%,91.43% and 0.921(95%CI: 0.856–0.985) for ADA in the course≤3 days group, respectively.

Conclusions ADA has a good diagnostic value in the early stage of atypical EBV infection, and is not affected by primary EBV infection and reactivation.

Schlüsselwörter Adenosine deaminase, Epstein -Barr virus, Biomarker, children.

Key words

Adenosine deaminase - Epstein-Barr virus - Biomarkerpublished online 2023

Full Text

References

References
1 de Thé G, Day N, Geser A. et al. Epidemiology of the Epstein-Barr virus infection and associated tumors in man. Bibl Haematol 1975; 216-220
2 Thompson MP, Kurzrock R. Epstein-Barr virus and cancer. Clin Cancer Res 2004; 10: 803-821
3 Balfour HH, Verghese P. Primary Epstein-Barr virus infection: impact of age at acquisition, coinfection, and viral load. J Infect Dis 2013; 207: 1787-1789
4 Dowd JB, Palermo T, Brite J. et al. Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6-19, 2003-2010. PLoS One 2013; 8: e64921
5 Cohen JI. Epstein-Barr virus infection. N Engl J Med 2000; 343: 481-492
6 Nowalk A, Green M. Epstein-Barr virus. Microbiol Spectr 2016; 4
7 Shi T, Huang L, Chen Z. et al. Characteristics of primary Epstein-Barr virus infection disease spectrum and its reactivation in children, in Suzhou, China. J Med Virol 2021; 93: 5048-5057
8 Hurt C, Tammaro D. Diagnostic evaluation of mononucleosis-like illnesses. Am J Med 2007; 120: 911.e1-8
9 Kanakry JA, Hegde AM, Durand CM. et al. The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases. Blood 2016; 127: 2007-2017
10 Antonioli L, Colucci R, La Motta C. et al. Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Curr Drug Targets 2012; 13: 842-862
11 Mejer J, Nygaard P, Cohn J. et al. Adenosine deaminase, purine nucleoside phosphorylase and 5’-nucleotidase activities in infectious mononucleosis. Adv Exp Med Biol 1984; 165: 249-252
12 Schiavetti A, Gonfiantini M, Varrasso G. et al. Atypical Epstein-Barr-virus infection in a 5-year-old girl. Minerva Pediatr 2009; 61: 115-117
13 Shi J, Ma W, Li W. Epidemiologic features of children with Epstein-Barr virus associated diseases in Hangzhou, China. J Med Virol 2020; 92: 1277-1282
14 Niller HH, Bauer G. Epstein-Barr virus: clinical diagnostics. Methods Mol Biol 2017; 1532: 33-55
15 AbuSalah M, Gan SH, Al-Hatamleh M. et al. Recent advances in diagnostic approaches for Epstein-Barr virus. Pathogens 2020; 9: 226
16 Shi T, Huang L, Luo L. et al. Diagnostic value of serological and molecular biological tests for infectious mononucleosis by EBV in different age stages and course of the disease. J Med Virol 2021; 93: 3824-3834
17 Singh L, Javali M, Mehta A. et al. Study of cerebrospinal fluid levels of lactate, lactate dehydrogenase and adenosine deaminase in the diagnosis and outcome of acute meningitis. Neurol Res 2022; 44: 463-467
18 Delemarre EM, van Hoorn L, Bossink A. et al. Serum biomarker profile including CCL1, CXCL10, VEGF, and adenosine deaminase activity distinguishes active from remotely acquired latent tuberculosis. Front Immunol 2021; 12: 725447
19 Bruu AL, Hjetland R, Holter E. et al. Evaluation of 12 commercial tests for detection of Epstein-Barr virus-specific and heterophile antibodies. Clin Diagn Lab Immunol 2000; 7: 451-456
20 Zavialov AV, Gracia E, Glaichenhaus N. et al. Human adenosine deaminase 2 induces differentiation of monocytes into macrophages and stimulates proliferation of T helper cells and macrophages. J Leukoc Biol 2010; 88: 279-290
21 Ghaderi B, Amini S, Maroofi F. et al. Adenosine deaminase activity in chronic lymphocytic leukemia and healthy subjects. Iran J Cancer Prev 2016; 9: e5069
22 Naval-Macabuhay I, Casanova V, Navarro G. et al. Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1. J Leukoc Biol 2016; 99: 349-359