Skip to main content
Top
Published in: Italian Journal of Pediatrics 1/2023

Open Access 01-12-2023 | Mononucleosis | Research

Concordance of adenosine deaminase with immunoglobulins and lymphocyte subsets in EBV-related diseases

Authors: Ting Shi, Qi Ding, Xinglou Liu, Guo Ai, Hua Zhou, Linlin Huang

Published in: Italian Journal of Pediatrics | Issue 1/2023

Login to get access

Abstract

Background

Clinical manifestations of Epstein–Barr virus (EBV) infection are diverse. This study aimed to explore the immune response in EBV-related diseases and the correlation between immune cells and adenosine deaminase (ADA) levels.

Methods

This study was conducted at the Children’s Hospital of Soochow University. In total, 104 patients with EBV-associated respiratory tract infection (EBV-RTI), 32 patients with atypical EBV infection, 54 patients with EBV-associated infectious mononucleosis (IM1, with normal alanine aminotransferase [ALT] levels), 50 patients with EBV-IM2 (with elevated ALT levels), 50 patients with acute respiratory infection (AURI, with other pathogens), and 30 healthy controls were enrolled in this study. Indicators of ADA, immunoglobulins (Igs), and lymphocyte subsets were analyzed for EBV-related diseases.

Results

Differences in the white blood cell, lymphocyte counts, ADA levels, IgA, IgG and IgM titers, percentage of CD3+, CD3+CD4+, CD3+CD8+, CD16+CD56+, CD3CD19+, and CD19+CD23+ lymphocytes, and CD4+/CD8+ ratio between EBV-related disease groups were all statistically significant (P < 0.01). ADA levels in the EBV-related disease groups were significantly higher than those in the control group (P < 0.01). The lymphocyte count, ADA levels, IgA and IgG titers, and percentage of CD3+ and CD3+CD8 + lymphocytes in the atypical EBV infection, EBV-IM1, and EBV-IM2 groups were significantly higher than those in the EBV-RTI, AUTI, and control groups (P < 0.01), whereas the percentage of CD3+CD4+, CD3CD19+, and CD19+CD23+ lymphocytes and CD4+/CD8+ ratio showed the opposite trend. ADA levels were consistent with and closely related to the viral load and cellular and humoral immunity in EBV-related diseases.

Conclusions

ADA levels, humoral immunity, and cellular immunity were diverse in EBV-related diseases, and ADA was closely related to Igs and lymphocyte subsets.
Literature
1.
3.
go back to reference Rostgaard K, Balfour HH Jr, Jarrett R, Erikstrup C, Pedersen O, Ullum H, et al. Primary Epstein-Barr virus infection with and without infectious mononucleosis. PLoS ONE. 2019;14:e0226436.CrossRefPubMedPubMedCentral Rostgaard K, Balfour HH Jr, Jarrett R, Erikstrup C, Pedersen O, Ullum H, et al. Primary Epstein-Barr virus infection with and without infectious mononucleosis. PLoS ONE. 2019;14:e0226436.CrossRefPubMedPubMedCentral
4.
go back to reference Kasahara Y, Yachie A. Cell type specific infection of Epstein-Barr virus (EBV) in EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Crit Rev Oncol Hematol. 2002;44:283–94.CrossRefPubMed Kasahara Y, Yachie A. Cell type specific infection of Epstein-Barr virus (EBV) in EBV-associated hemophagocytic lymphohistiocytosis and chronic active EBV infection. Crit Rev Oncol Hematol. 2002;44:283–94.CrossRefPubMed
5.
go back to reference Shi T, Huang L, Chen Z, Tian J. Characteristics of primary Epstein-Barr virus infection disease spectrum and its reactivation in children, in Suzhou, China. J Med Virol. 2021;93:5048–57.CrossRefPubMed Shi T, Huang L, Chen Z, Tian J. Characteristics of primary Epstein-Barr virus infection disease spectrum and its reactivation in children, in Suzhou, China. J Med Virol. 2021;93:5048–57.CrossRefPubMed
6.
7.
go back to reference Balfour HH Jr, Odumade OA, Schmeling DO, Mullan BD, Ed JA, Knight JA, et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis. 2013;207:80–8.CrossRefPubMed Balfour HH Jr, Odumade OA, Schmeling DO, Mullan BD, Ed JA, Knight JA, et al. Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis. 2013;207:80–8.CrossRefPubMed
9.
go back to reference Houssaint E, Saulquin X, Scotet E, Bonneville M. Immunodominant CD8 T cell response to Epstein-Barr virus. Biomed Pharmacother. 2001;55:373–80.CrossRefPubMed Houssaint E, Saulquin X, Scotet E, Bonneville M. Immunodominant CD8 T cell response to Epstein-Barr virus. Biomed Pharmacother. 2001;55:373–80.CrossRefPubMed
11.
go back to reference Cortés A, Gracia E, Moreno E, et al. Moonlighting adenosine deaminase: a target protein for drug development. Med Res Rev. 2015;35(1):85–125.CrossRefPubMed Cortés A, Gracia E, Moreno E, et al. Moonlighting adenosine deaminase: a target protein for drug development. Med Res Rev. 2015;35(1):85–125.CrossRefPubMed
12.
go back to reference Antonioli L, Colucci R, La Motta C, Tuccori M, Awwad O, Da Settimo F, 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;13:842–62.CrossRefPubMed Antonioli L, Colucci R, La Motta C, Tuccori M, Awwad O, Da Settimo F, 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;13:842–62.CrossRefPubMed
13.
go back to reference Mejer J, Nygaard P, Cohn J, Gadeberg O, Faber V. Adenosine deaminase, purine nucleoside phosphorylase and 5’-nucleotidase activities in infectious mononucleosis. Adv Exp Med Biol. 1984;165:249–52. Pt A: 249 – 52.CrossRefPubMed Mejer J, Nygaard P, Cohn J, Gadeberg O, Faber V. Adenosine deaminase, purine nucleoside phosphorylase and 5’-nucleotidase activities in infectious mononucleosis. Adv Exp Med Biol. 1984;165:249–52. Pt A: 249 – 52.CrossRefPubMed
14.
go back to reference Shi T, Li J, Miao Y, et al. Adenosine deaminase as a marker for the severity of infectious mononucleosis secondary to EBV in children. BMC Infect Dis. 2022;22:876–85.CrossRef Shi T, Li J, Miao Y, et al. Adenosine deaminase as a marker for the severity of infectious mononucleosis secondary to EBV in children. BMC Infect Dis. 2022;22:876–85.CrossRef
15.
go back to reference Shi J, Ma W, Li W. Epidemiologic features of children with Epstein-Barr virus associated diseases in Hangzhou, China. J Med Virol. 2020;92:1277–82.CrossRefPubMed Shi J, Ma W, Li W. Epidemiologic features of children with Epstein-Barr virus associated diseases in Hangzhou, China. J Med Virol. 2020;92:1277–82.CrossRefPubMed
16.
go back to reference Odame J, Robinson J, Khodai-Booran N, Yeung S, Mazzulli T, Stephens D, et al. Correlates of illness severity in infectious mononucleosis. Can J Infect Dis Med Microbiol. 2014;25:277–80.CrossRefPubMedPubMedCentral Odame J, Robinson J, Khodai-Booran N, Yeung S, Mazzulli T, Stephens D, et al. Correlates of illness severity in infectious mononucleosis. Can J Infect Dis Med Microbiol. 2014;25:277–80.CrossRefPubMedPubMedCentral
17.
go back to reference Jayasooriya S, de Silva TI, Njie-jobe J, Sanyang C, Leese AM, Bell AI, et al. Early virological and immunological events in asymptomatic Epstein-Barr virus infection in african children. PLOS Pathog. 2015;11:e1004746.CrossRefPubMedPubMedCentral Jayasooriya S, de Silva TI, Njie-jobe J, Sanyang C, Leese AM, Bell AI, et al. Early virological and immunological events in asymptomatic Epstein-Barr virus infection in african children. PLOS Pathog. 2015;11:e1004746.CrossRefPubMedPubMedCentral
19.
go back to reference Houen G, Trier NH. Epstein-Barr Virus and systemic Autoimmune Diseases. Front Immunol. 2020;11:587380.CrossRefPubMed Houen G, Trier NH. Epstein-Barr Virus and systemic Autoimmune Diseases. Front Immunol. 2020;11:587380.CrossRefPubMed
20.
go back to reference Kakalacheva K, Regenass S, Wiesmayr S et al. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein. Viruses. 2016. 8(2). Kakalacheva K, Regenass S, Wiesmayr S et al. Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein. Viruses. 2016. 8(2).
21.
go back to reference Ben-Chetrit E, Wiener-Well Y, Fadeela A, Wolf DG. Antiphospholipid antibodies during infectious mononucleosis and their long term clinical significance. J Clin Virol. 2013;56(4):312–5.CrossRefPubMed Ben-Chetrit E, Wiener-Well Y, Fadeela A, Wolf DG. Antiphospholipid antibodies during infectious mononucleosis and their long term clinical significance. J Clin Virol. 2013;56(4):312–5.CrossRefPubMed
22.
go back to reference Sutton RN, Emond RT, Thomas DB, Doniach D. The occurrence of autoantibodies in infectious mononucleosis. Clin Exp Immunol. 1974;17:427–36.PubMedPubMedCentral Sutton RN, Emond RT, Thomas DB, Doniach D. The occurrence of autoantibodies in infectious mononucleosis. Clin Exp Immunol. 1974;17:427–36.PubMedPubMedCentral
23.
go back to reference Long HM, Chagoury OL, Leese AM, Ryan GB, James E, Morton LT, et al. MHC II tetramers visualize human CD4 + T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response. J Exp Med. 2013;210:933–49.CrossRefPubMedPubMedCentral Long HM, Chagoury OL, Leese AM, Ryan GB, James E, Morton LT, et al. MHC II tetramers visualize human CD4 + T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response. J Exp Med. 2013;210:933–49.CrossRefPubMedPubMedCentral
24.
go back to reference Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: Lessons from Epstein-Barr virus. Annu Rev Immunol. 2007;25:587–617.CrossRefPubMed Hislop AD, Taylor GS, Sauce D, Rickinson AB. Cellular responses to viral infection in humans: Lessons from Epstein-Barr virus. Annu Rev Immunol. 2007;25:587–617.CrossRefPubMed
25.
go back to reference Barros MHM, Vera-Lozada G, Segges P, Hassan R, Niedobitek G. Revisiting the tissue microenvironment of infectious mononucleosis: identification of EBV infection in T cells and deep characterization of immune profiles. Front Immunol. 2019;10:146.CrossRefPubMedPubMedCentral Barros MHM, Vera-Lozada G, Segges P, Hassan R, Niedobitek G. Revisiting the tissue microenvironment of infectious mononucleosis: identification of EBV infection in T cells and deep characterization of immune profiles. Front Immunol. 2019;10:146.CrossRefPubMedPubMedCentral
26.
go back to reference Lam JKP, Hui KF, Ning RJ, Xu XQ, Chan KH, Chiang AKS. Emergence of CD4 + and CD8 + polyfunctional T cell responses against immunodominant lytic and latent EBV antigens in children with primary EBV infection. Front Microbiol. 2018;9:416.CrossRefPubMedPubMedCentral Lam JKP, Hui KF, Ning RJ, Xu XQ, Chan KH, Chiang AKS. Emergence of CD4 + and CD8 + polyfunctional T cell responses against immunodominant lytic and latent EBV antigens in children with primary EBV infection. Front Microbiol. 2018;9:416.CrossRefPubMedPubMedCentral
27.
go back to reference Hendricks DW, Balfour HH Jr, Dunmire SK, Schmeling DO, Hogquist KA, Lanier LL. Cutting edge: NKG2C(hi)CD57 + NK cells respond specifically to acute infection with cytomegalovirus and not Epstein-Barr virus. J Immunol. 2014;192:4492–6.CrossRefPubMed Hendricks DW, Balfour HH Jr, Dunmire SK, Schmeling DO, Hogquist KA, Lanier LL. Cutting edge: NKG2C(hi)CD57 + NK cells respond specifically to acute infection with cytomegalovirus and not Epstein-Barr virus. J Immunol. 2014;192:4492–6.CrossRefPubMed
28.
go back to reference Strowig T, Brilot F, Arrey F, Bougras G, Thomas D, Muller WA, et al. Tonsilar NK cells restrict B cell transformation by the Epstein-Barr virus via IFN-gamma. PLOS Pathog. 2008;4:e27.CrossRefPubMedPubMedCentral Strowig T, Brilot F, Arrey F, Bougras G, Thomas D, Muller WA, et al. Tonsilar NK cells restrict B cell transformation by the Epstein-Barr virus via IFN-gamma. PLOS Pathog. 2008;4:e27.CrossRefPubMedPubMedCentral
29.
go back to reference Yu DM, Slaitini L, Gysbers V, Riekhoff AG, Kähne T, Knott HM, et al. Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding. Scand J Immunol. 2011;73:102–11.CrossRefPubMed Yu DM, Slaitini L, Gysbers V, Riekhoff AG, Kähne T, Knott HM, et al. Soluble CD26 / dipeptidyl peptidase IV enhances human lymphocyte proliferation in vitro independent of dipeptidyl peptidase enzyme activity and adenosine deaminase binding. Scand J Immunol. 2011;73:102–11.CrossRefPubMed
30.
go back to reference Moreno E, Canet J, Gracia E, Lluís C, Mallol J, Canela EI, et al. Molecular evidence of adenosine deaminase linking adenosine A2a receptor and CD26 proteins. Front Pharmacol. 2018;9:106.CrossRefPubMedPubMedCentral Moreno E, Canet J, Gracia E, Lluís C, Mallol J, Canela EI, et al. Molecular evidence of adenosine deaminase linking adenosine A2a receptor and CD26 proteins. Front Pharmacol. 2018;9:106.CrossRefPubMedPubMedCentral
31.
go back to reference Lamontagne RJ, Soldan SS, Su C, Wiedmer A, Won KJ, Lu F, et al. A multi-omics approach to Epstein-Barr virus immortalization of B-cells reveals EBNA1 chromatin pionering activities targeting nucleotide metabolism. PLOS Pathog. 2021;17:e1009208.CrossRefPubMedPubMedCentral Lamontagne RJ, Soldan SS, Su C, Wiedmer A, Won KJ, Lu F, et al. A multi-omics approach to Epstein-Barr virus immortalization of B-cells reveals EBNA1 chromatin pionering activities targeting nucleotide metabolism. PLOS Pathog. 2021;17:e1009208.CrossRefPubMedPubMedCentral
Metadata
Title
Concordance of adenosine deaminase with immunoglobulins and lymphocyte subsets in EBV-related diseases
Authors
Ting Shi
Qi Ding
Xinglou Liu
Guo Ai
Hua Zhou
Linlin Huang
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Italian Journal of Pediatrics / Issue 1/2023
Electronic ISSN: 1824-7288
DOI
https://doi.org/10.1186/s13052-023-01457-0

Other articles of this Issue 1/2023

Italian Journal of Pediatrics 1/2023 Go to the issue