Clinical and diagnostic significance of determining the cytokine status in infants with chronic cytomegalovirus infection against the background of hypoxic-ischemic CNS damage

Objective: based on the production of cytokines, to identify the immunological features of the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage.

Research methods:108 newborns with cytomegalovirus infection occurring against the background of perinatal hypoxic-ischemic lesions of the central unequal system were examined. All observed patients immediately after the diagnosis of cytomegalovirus infection underwent an immunological examination, including the determination of the levels of interferon-alpha (IFN-α) and interferon-gamma (IFN-γ), the level of interleukins — 2 and 4 (IL -2 and IL-4) necrosis factor human alpha tumors (TNF-α in blood serum was determined by enzyme immunoassay using a set of reagents ProCon IF2 plus, ProCon Ifgamma, ProCon TNFα (Protein contour LLC, Russia, St. Petersburg). At 1 and 6 months of life .

The observation groups consisted of 78 children (72.2%) with an acute course of the disease (Group 1) and 30 children (27.3%) with a chronic course (Group 2). The control group consisted of 15 newborns without herpes virus infection.

Results. Of the totality of the studied cytokines, statistically significant for the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage were found: IL-2, IFN-γ. It was found that in children with a persistent low level of IFN-γ and an increased level of IL-4 in the blood serum at the age of 6 months, there was a chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage.

A decrease in IFN-γ production indicates a congenital or acquired deficiency of the interferon system and can be considered as an indication for long-term interferon replacement therapy.

1. Karpova A.L., Narogan M.V., Karpov N.Yu. Congenital cytomegalovirus infection: diagnosis, treatment, and prevention. Rossiyskiy Vestnik Perinatologii i Pediatrii =Russian Bulletin of Perinatology and Pediatrics. 2017; 62(1):10—18. (in Russ). DOI: 10.21508/1027-4065-2017-62-1-10-18

2. Kravchenko L.V. Levkovich M.A., Pyatikova M.V. The role of polymorphism of the interferon-γ gene and interferonoproduction in the pathogenesis of infection caused by herpes 6 type virus in children of early age. Klinicheskaya Laboratornaya Diagnostika=Russian Clinical Laboratory Diagnostics. 2018; 63(6): 357—361. (in Russ). DOI: http://dx.doi.org/10.18821/0869-2084-2018-63-6-357-361

3. Vatazin А.V., Zul’karnaev А.B., FedulkinaV.А., Krstic М. Major intercellular interactions at the t cell activation in renaltransplant rejection Al'manakhoy Klinicheskoy Meditsiny=Almanac of Clinical Medicine. 2014; 3:76—82. (in Russ)

4. Kravchenko L.V., Levkovich M.A. Mechanisms of immunno-supression upon frequent acute viral respiratory infections in infants after neonatal cytomegalovirus infectoin. VICH-Infektsiya i Immunosupressii= HIV Infection and Immunosuppressive Disorders. 2017; 3(9):34—38. (in Russ.)

5. Sennikov S.V., Kulikova E.V., Knauer N.Y., Khantakova Y.N. Molecular and cellular mechanisms mediated by dendritic cells involved in the induction of tolerance. Meditsinskaya Immunologiya=Medical Immunology. 2017; 19(4):59—374. (in Russ). DOI:org/10.15789/1563-0625-2017-4-359-374

6. Yarilin A.A. Immunology. Moscow: GEOTAR-Media, 2010:752. (in Russ)

7. Kravchenko L.V. A role of impaired neonatal T cell activation upon late CMV detection. Infektsiya i Immunitet=Russian Journal of Infection andImmunity. 2019; 9(2):288—294. (in Russ). DOI: [10.15789/2220-7619-2019- 2-288-294

8. Sizyakina L.P., Kharitonova M.V. Characteristics of B2 lymphocytes in patients with seropositive rheumatoidarthritis articular form. Immunologiya= Immunologiya. 2017; 38(4):226—228. (in Russ). DOI: http://dx.doi.org/10.18821/0206-4952-2017-38-4-226-228

9. Berthelot J.M., Jamin C., Amrouche K. Regulatory B cells play a key role in immune system balance. Joint Bone Spine. 2013; 80(1): 18—22.

10. Candando K.M., J.M. Lykken, T.F. Tedder. B10 cell regulation of health and disease. Immunol. Rev. 2014; 259(1):259—272.

11. Royt A., J. Brosoff, D. Mail. Immunology. M.: Mir, 2000:593. (in Russ)

12. Kushnareva M.V., Vinogradova T.V., Keshishian E.S., Parfenov V.V., Koltsov V.D., Bragina G.S., Parshina O.V., Guseva T.S. Specific features of the immune status and interferon system of infants. Rossiyskiy Vestnik Perinatologii i Pediatrii=Russian Bulletin of Perinatology and Pediatrics. 2016; 61(3):12—21. (In Russ.) https://doi.org/10.21508/1027-4065-2016-61-3-12-21