Structural and functional state of blood lymphocytes in patients with infectious mononucleosis with different course
DOI:
https://doi.org/10.14739/2310-1237.2021.3.239166Keywords:
children, infectious mononucleosis, structure, immunity, lymphocyte, prognosis of the courseAbstract
The article presents the results of our own studies.
The aim was to determine the structural and functional status of blood lymphocytes in patients with acute and prolonged course of infectious mononucleosis (IM) in children.
Materials and methods. 102 children were under clinical and laboratory-instrumental supervision, the children were divided into groups: group 1 – 65 children with IM with an acute course of the disease; group 2 – 37 children with a prolonged course of the disease. All children underwent standard clinical laboratory and instrumental laboratory examinations. The diagnosis of IM was confirmed by PCR (detection of EBV DNA in the blood) and ELISA (anti-EBV IgM and IgG).
Research results. In the study of the structural state of the cytoplasmic membrane of the lymphocytes in the blood of patients with MI in the onset of the disease, it was found that the average values of penetration rate of the electron paramagnetic resonance of spin probes (PR EPR s. p.) in children of both groups were significantly higher than normal (P < 0.001). There are also differences between groups of patients. In this case, the value of PR EPR s. p. in patients with a prolonged course by 15.8 % exceeded those in patients with acute IM (P < 0.001). According to the rate of microviscosity of the intracellular content (MV IC), its values were reduced compared with the control – by 22.1 % (P < 0.001) in patients with acute course of the disease and by 25.1 % – with a prolonged course of IM). In addition, in patients with a prolonged course of the disease, the values were 9 % lower than in the group with acute infectious mononucleosis. When considering immunological parameters, it was found that the indicators of the T-immune system for patients with a prolonged course of the disease in comparison with the alternative group was characterized by a decrease in the content of CD3 <50 % (respectively in 51.3 % and 26.2 % of patients; P < 0.05); CD4 <31 % (62.1 % and 32.4 %, respectively; P < 0.05) and CD8 <15 % (37.8 % and 10.8 %, respectively; P < 0.01). With regard to the cytokine profile, the level of IL-1 <20.0 pg/ml was determined 3.5 times more often in patients with a prolonged course of the disease compared to the acute course (64.8 % and 18.5 % of patients, respectively); TNFα <20.0 pg/ml 1.9 times more often (48.6 % and 24.6 %, respectively) and a very high (>30.1 pg/ml) level of IL4 in 40.5 % and 20 %). From the B-system of immunity in patients with a prolonged course of IM in comparison with the acute course increased content of CD22 was more often determined, as well as low levels of IgA, IgM <1.1 g/l and IgG <10.0 g/l.
Conclusions. According to the results of observations, the pathogenetic role of the violation of the structural organization of blood lymphocytes in the formation of IM is established. It was found that these disorders in the form of increased permeability of their cytoplasmic membrane and reduced viscoelastic properties of their intracellular environment are more pronounced with a prolonged course of the disease, which is a factor in the prolongation of the disease. It is determined that the indicators of cellular and humoral parts of the immune system affect the course of IM. During formation of an acute course of IM in children already in the acute period of a disease activation of both cellular and humoral links of immunity, which is shown in the form of increase in relative content of CD3+, CD4+, CD8+ and CD22+ and levels of immunoglobulins M, A, is noted. For the prolonged course of the disease depression of T-cell immunity in the form of a decrease in the relative content of CD3+, CD4+ and CD8+ lymphocytes and an increase in CD22+, as well as inhibition of antibody genesis are characteristic. It was found that the variant of IM depends on the type of reaction of T-helper clones, namely – in the initial period of manifestation of IM with its acute course there is activation of T1 and T2 helper response, which manifests itself in a significant increase in IL-1, TNFα and moderate IL-4. Prolonged course of the disease is formed against the background of weak activation of pro-inflammatory interleukins (IL-1, TNFα) and significant – anti-inflammatory IL-4.
References
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
Kuri, A., Jacobs, B. M., Vickaryous, N., Pakpoor, J., Middeldorp, J., Giovannoni, G., & Dobson, R. (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
Rostgaard, K., Balfour, H. H., Jr, Jarrett, R., Erikstrup, C., Pedersen, O., Ullum, H., Nielsen, L. P., Voldstedlund, M., & Hjalgrim, H. (2019). Primary Epstein-Barr virus infection with and without infectious mononucleosis. PloS one, 14(12), e0226436. https://doi.org/10.1371/journal.pone.0226436
Ebell, M. (2016). Infectious Mononucleosis. JAMA, 315(14), 1532.
Ishii, T., Sasaki, Y., Maeda, T., Komatsu, F., Suzuki, T., & Urita, Y. (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
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
Stanfield, B. A., & Luftig, M. A. (2017). Recent advances in understanding Epstein-Barr virus. F1000Research, 6, 386. https://doi.org/10.12688/f1000research.10591.1
Long, H. M., Meckiff, B. J., & Taylor, G. S. (2019). The T-cell Response to Epstein-Barr Virus-New Tricks From an Old Dog. Frontiers in immunology, 10, 2193. https://doi.org/10.3389/fimmu.2019.02193
Barros, M., Vera-Lozada, G., Segges, P., Hassan, R., & Niedobitek, G. (2019). Revisiting the Tissue Microenvironment of Infectious Mononucleosis: Identification of EBV Infection in T Cells and Deep Characterization of Immune Profiles. Frontiers in immunology, 10, 146. https://doi.org/10.3389/fimmu.2019.00146
Siliézar, M. M., Muñoz, C. C., Solano-Iturri, J. D., Ortega-Comunian, L., Mollejo, M., Montes-Moreno, S., & Piris, M. A. (2018). Spontaneously Ruptured Spleen Samples in Patients With Infectious Mononucleosis: Analysis of Histology and Lymphoid Subpopulations. American journal of clinical pathology, 150(4), 310-317. https://doi.org/10.1093/ajcp/aqy056
Hayashida, M., Daibata, M., Tagami, E., Taguchi, T., Maekawa, F., Takeoka, K., Fukutsuka, K., Shimomura, D., Hayashi, T., Iwatani, Y., & Ohno, H. (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
Cohen, J. I., Iwatsuki, K., Ko, Y. H., Kimura, H., Manoli, I., Ohshima, K., Pittaluga, S., Quintanilla-Martinez, L., & Jaffe, E. S. (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
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
Ko, Y.-H. (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
Chen, L., Chen, X., Yao, W., Wei, X., Jiang, Y., Guan, J., Liu, X., Xie, Y., Lu, H., Qian, J., Zhang, Z., Wu, L., & Lin, X. (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
Brustolon, M., & Giamello, E. (Eds.). (2009). Electron paramagnetic resonance. Hoboken, N.J: John Wiley & Sons, Inc.
Arashiki, N., & Takakuwa, Y. (2017). Maintenance and regulation of asymmetric phospholipid distribution in human erythrocyte membranes: implications for erythrocyte functions. Current opinion in hematology, 24(3), 167-172. https://doi.org/10.1097/MOH.0000000000000326
Sezgin, E., Levental, I., Mayor, S., & Eggeling, C. (2017). The mystery of membrane organization: composition, regulation and roles of lipid rafts. Nature reviews. Molecular cell biology, 18(6), 361-374. https://doi.org/10.1038/nrm.2017.16
Harvey, J. M., Broderick, G., Bowie, A., Barnes, Z. M., Katz, B. Z., O'Gorman, M., Vernon, S. D., Fletcher, M. A., Klimas, N. G., & Taylor, R. (2016). Tracking post-infectious fatigue in clinic using routine Lab tests. BMC pediatrics, 16, 54. https://doi.org/10.1186/s12887-016-0596-8
Baxter, A. A., Poon, I. K., & Hulett, M. D. (2017). The lure of the lipids: how defensins exploit membrane phospholipids to induce cytolysis in target cells. Cell death & disease, 8(3), e2712. https://doi.org/10.1038/cddis.2017.69
Degreif, D., de Rond, T., Bertl, A., Keasling, J. D., & Budin, I. (2017). Lipid engineering reveals regulatory roles for membrane fluidity in yeast flocculation and oxygen-limited growth. Metabolic engineering, 41, 46-56. https://doi.org/10.1016/j.ymben.2017.03.002
Chen M. R. (2011). Epstein-barr virus, the immune system, and associated diseases. Frontiers in microbiology, 2, 5. https://doi.org/10.3389/fmicb.2011.00005
Merlo, A., Turrini, R., Dolcetti, R., Martorelli, D., Muraro, E., Comoli, P., & Rosato, A. (2010). The interplay between Epstein-Barr virus and the immune system: a rationale for adoptive cell therapy of EBV-related disorders. Haematologica, 95(10), 1769-1777. https://doi.org/10.3324/haematol.2010.023689
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, 88, 31-33. https://doi.org/10.1016/j.ijid.2019.07.039
Kimura, H., Morishima, T., Kanegane, H., Ohga, S., Hoshino, Y., Maeda, A., Imai, S., Okano, M., Morio, T., Yokota, S., Tsuchiya, S., Yachie, A., Imashuku, S., Kawa, K., Wakiguchi, H., & Japanese Association for Research on Epstein-Barr Virus and Related Diseases (2003). Prognostic factors for chronic active Epstein-Barr virus infection. The Journal of infectious diseases, 187(4), 527-533. https://doi.org/10.1086/367988
Fukuda, M., & Kawaguchi, Y. (2014). Role of the immunoreceptor tyrosine-based activation motif of latent membrane protein 2A (LMP2A) in Epstein-Barr virus LMP2A-induced cell transformation. Journal of virology, 88(9), 5189-5194. https://doi.org/10.1128/JVI.03714-13
Fish, K., Chen, J., & Longnecker, R. (2014). Epstein-Barr virus latent membrane protein 2A enhances MYC-driven cell cycle progression in a mouse model of B lymphoma. Blood, 123(4), 530-540. https://doi.org/10.1182/blood-2013-07-517649
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
Chiereghin, A., Piccirilli, G., Belotti, T., Prete, A., Bertuzzi, C., Gibertoni, D., Gabrielli, L., Turello, G., Borgatti, E. C., Barbato, F., Sessa, M., Arpinati, M., Bonifazi, F., & Lazzarotto, T. (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
Tangye, S. G., Palendira, U., & Edwards, E. S. (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
Downloads
Published
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (SeeThe Effect of Open Access).
