Ukrainian Journal of Perinatology and Pediatrics. 2025.3(103): 108-114. doi: 10.15574/PP.2025.3(103).108114
Kolesnyk Ya. V., Olkhovska O. M., Slepchenko M. Yu.
Kharkiv National Medical University, Ukraine

For citation: Kolesnyk YaV, Olkhovska OM, Slepchenko MYu. (2025). Clinical and immunological differences of infectious mononucleosis in children with acute and prolonged course of the disease. Ukrainian Journal of Perinatology and Pediatrics. 3(103): 108-114. doi: 10.15574/PP.2025.3(103).108114.
Article received: Mar 21, 2025. Accepted for publication: Sep 15, 2025.

The basis for conducting the study was the absence in the scientific literature of works devoted to the study of clinical and immunological differences of infectious mononucleosis (IM) in children with an acute and protracted course of the disease.
The aim – to determine the clinical and immunological differences of IM in children with acute and prolonged courses in order to improve therapy and rehabilitation of patients.
Materials and methods. A total of 102 children were under clinical and laboratory-instrumental supervision, of which 65 children (group 1) had acute IM, and 37 (group 2) had a prolonged course.
Results. The severity of lymphoproliferative and hepatosplenic syndromes at the onset of IM can be used as one of the criteria for the probable development of a prolonged course of the disease. The formation of a protracted course is accompanied by a decrease in the content of CD3 less than 50%; CD4 less than 31% and CD8 less than 15%, as well as an increase in the levels of interleukin 1 (IL1) over 20.0 pg/ml (3.5 times more often compared to the group 1), tumor necrosis factor α (TNFα) up to 20.0 pg/ml (1.9 times more often) and a very high level of interleukin 4 (IL4) – over 30.1 pg/ml. Patients of the group 2 were characterized by increased CD22 levels, low levels of immunoglobulins (Ig) IgA, IgM (less than 1.1 g/l), and IgG (less than 10.0 g/l).
Conclusions. Indicators of cellular and humoral immunity influence the course of IM. The formation of the acute course of IM in children is accompanied by activation of both cellular and humoral immunity at the onset of the disease. The prolonged course of IM is characterized by depression of the T-cell link of immunity, as well as inhibition of antibody genesis. The prolonged course of the disease is formed against the background of weak activation of pro-inflammatory interleukins (IL1, TNFα) and significant – anti-inflammatory IL4.
The research was carried out in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of the institution mentioned in the paper. The informed consent of the patient was obtained for conducting the studies.
No conflict of interests was declared by the authors.
Keywords: children, infectious mononucleosis, immunity.

REFERENCES

1. Cen O, Longnecker R. (2015). Latent Membrane Protein 2 (LMP2). Current topics in microbiology and immunology. 391: 151-180. https://doi.org/10.1007/978-3-319-22834-1_5; PMid:26428374

2. Chen L, Chen X, Yao W, Wei X, Jiang Y, Guan J et al. (2021). Dynamic Distribution and Clinical Value of Peripheral Lymphocyte Subsets in Children with Infectious Mononucleosis. Indian journal of pediatrics. 88(2): 113-119. https://doi.org/10.1007/s12098-020-03319-7; PMid:32472349

3. Chiereghin A, Piccirilli G, Belotti T, Prete A, Bertuzzi C, Gibertoni D et al. (2019). Clinical utility of measuring Epstein-Barr virus-specific cell-mediated immunity after HSCT in addition to virological monitoring: results from a prospective study. Medical microbiology and immunology. 208(6): 825-834. https://doi.org/10.1007/s00430-019-00629-2; PMid:31289930

4. Cohen JI, Iwatsuki K, Ko YH, Kimura H, Manoli I, Ohshima K et al. (2020). Epstein-Barr virus NK and T cell lymphoproliferative disease: report of a 2018 international meeting. Leukemia & lymphoma. 61(4): 808-819. https://doi.org/10.1080/10428194.2019.1699080; PMid:31833428 PMCid:PMC8189159

5. Dralova OA, Usachova OV, Pakholchuk TM, Konakova OV, Silina EA. (2019). Infectious mononucleosis: the multiplicity of manifestations. A clinical case of a severe course of infectious mononucleosis in an infant. Modern Pediatrics. Ukraine. 7(103): 63-66. https://doi.org/10.15574/SP.2019.103.63

6. Ebell MH. (2016). JAMA Patient page. Infectious Mononucleosis. JAMA. 315(14): 1532. https://doi.org/10.1001/jama.2016.2474; PMid:27115282

7. Fujiwara S, Nakamura H. (2020). Chronic Active Epstein-Barr Virus Infection: Is It Immunodeficiency. Malignancy, or Both? Cancers. 12(11): 3202. https://doi.org/10.3390/cancers12113202; PMid:33143184 PMCid:PMC7692233

8. Guz O, Kuznetsov S. (2020). The value of the microbial flora of the nasal and oropharyngeal mucosa in the formation of clinical and immunological features of infectious mononucleosis in children. Inter Collegas. 3: 146-151. https://doi.org/10.35339/ic.7.3.146-151

9. Harvey JM, Broderick G, Bowie A, Barnes ZM, Katz BZ, O'Gorman MRG et al. (2016). Tracking post-infectious fatigue in clinic using routine Lab tests. BMC pediatrics. 16: 54. https://doi.org/10.1186/s12887-016-0596-8; PMid:27118537 PMCid:PMC4847210

10. Hayashida M, Daibata M, Tagami E, Taguchi T, Maekawa F, Takeoka K et al. (2017). Establishment and characterization of a novel Hodgkin lymphoma cell line, AM-HLH, carrying the Epstein-Barr virus genome integrated into the host chromosome. Hematological oncology. 35(4): 567-575. https://doi.org/10.1002/hon.2369; PMid:27813134

11. Iemura T, Kondo T, Hishizawa M, Yamashita K, Kimura H, Takaori-Kondo A. (2019). NK-cell post-transplant lymphoproliferative disease with chronic active Epstein-Barr virus infection-like clinical findings. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 88: 31-33. https://doi.org/10.1016/j.ijid.2019.07.039; PMid:31398454

12. Ionov IA, Komisova TIe, Sukach OM, Katerynych OO. (2017). Suchasna imunolohiia. Kurs lektsii dlia stud. vyshch. navch. zakl. Kharkiv: ChP Petrov V.V.: 107. URL: http://dspace.hnpu.edu.ua/handle/123456789/765.

13. Ishii T, Sasaki Y, Maeda T et. al. (2019). Clinical differentiation of infectious mononucleosis that is caused by Epstein-Barr virus or cytomegalovirus: A single-center case-control study in Japan. Journal of Infection and Chemotherapy. 25(6): 431-436. https://doi.org/10.1016/j.jiac.2019.01.012; PMid:30773381 PMCid:PMC7128249

14. Kimura H, Fujiwara S. (2019). Overview of EBV-Associated T/NK-Cell Lymphoproliferative Diseases. Frontiers in pediatrics. 6: 417. https://doi.org/10.3389/fped.2018.00417; PMid:30662890 PMCid:PMC6328478

15. Ko Y. (2018). Epstein-Barr virus-positive T/NK-cell lymphoproliferative diseases in children and adolescents. Precision and Future Medicine. 2(1): 1-7. https://doi.org/10.23838/pfm.2017.00198

16. Kuri A, Jacobs BM, Vickaryous N, Pakpoor J, Middeldorp J et al. (2020). Epidemiology of Epstein-Barr virus infection and infectious mononucleosis in the United Kingdom. BMC public health. 20(1): 912. https://doi.org/10.1186/s12889-020-09049-x; PMid:32532296 PMCid:PMC7291753

17. Kuryliv HM, Drohomeretska OІ, Iakubovska IO. (2019). Otsinka imunolohichnykh porushen u khvorykh na v-klitynnu khronichnu limfotsytarnu leikemiiu. Art of medicine. 1: 62-65.

18. Popov MM, Liadova TI, Volobuieva OV, Sorokina OH, Pavlikova KV. (2022). Features of the course of infectious mononucleosis caused by epstiein-barr virus. Immunology and Allergology: Science and Practice. (1-2): 59-64. https://doi.org/10.37321/immunology.2022.1-2-07

19. Rostgaard K, Balfour HH Jr, Jarrett R, Erikstrup C, Pedersen O, Ullum H et al. (2019). Primary Epstein-Barr virus infection with and without infectious mononucleosis. PloS one. 14(12): e0226436. https://doi.org/10.1371/journal.pone.0226436; PMid:31846480 PMCid:PMC6917282

20. Simre K, Uibo O, Peet A, Puustinen L, Oikarainen S, Tamminen K et al. (2019). Early-life exposure to common virus infections did not differ between coeliac disease patients and controls. Acta paediatrica (Oslo, Norway : 1992). 108(9): 1709-1716. https://doi.org/10.1111/apa.14791; PMid:30896051

21. Smoliar NI, Chukhrai NL, Savchyn SV. (2019). Epshteina-Barr virusna infektsiia u ditei. Aktualni problemy suchasnoi medytsyny. 19; 1(65): 43-47. https://doi.org/10.31718/2077-1096.19.1.43

22. Sorokman TV, Popeliuk O-MV, Parfonova IV, Zymahorova NO. (2016). Osoblyvosti urazhennia pechinky pry infektsionnomu mononukleozi v ditei. Aktualna infektolohiia. 2(11): 177-181. https://doi.org/10.22141/2312-413x.2.11.2016.77667

23. Stanfield BA, Luftig MA. (2017). Recent advances in understanding Epstein-Barr virus. F1000 Research. 6: 386. https://doi.org/10.12688/f1000research.10591.1; PMid:28408983 PMCid:PMC5373418

24. Tangye SG, Palendira U, Edwards ES. (2017). Human immunity against EBV-lessons from the clinic. The Journal of experimental medicine. 214(2): 269-283. https://doi.org/10.1084/jem.20161846; PMid:28108590 PMCid:PMC5294862

25. Yang Y, Gao F. (2020). Clinical characteristics of primary and reactivated Epstein-Barr virus infection in children. Journal of medical virology. 92(12): 3709-3716. https://doi.org/10.1002/jmv.26202; PMid:32558948

26. Zaretska AV. (2020). Epidemiolohiia, suchasni osoblyvosti diahnostyky, кlinichnoho perebihu, korektsii patolohichnykh zrushen ta prohnoz infektsiinoho mononukleozu herpesvirusnoi etiolohii v ditei. Dys. d-ra filosofii: 14.01.10. Odeskyi natsionalnyi medychnyi universytet: 202.