Assessment of neuronal antibodies levels and cytokine profile in healthcare professionals

A review of research in the field of occupational medicine shows that one of the central places in it is occupied by a comprehensive diagnosis of an employee's health status, especially in situations of severe and prolonged stress, which often leads to complete or partial professional burnout. The profession of a medical professional occupies a key place among specialties with a high risk of occupational stress. The consequences of occupational stress are closely related to the threat of developing various diseases of the nervous, cardiovascular, immune and endocrine systems. There is a growing interest in the importance of antibodies to specialized structures of nervous tissue, which are considered as new-generation biomarkers in a number of neurological disorders. A significant number of studies show the role of the cytokine network in the pathogenesis of anxiety and depressive disorders caused by stress.

The study aims to evaluate the serum concentrations of antibodies to regulatory proteins of the nervous tissue, pro- and anti-inflammatory cytokines and their interrelationships in the secondary medical staff to substantiate the early immunochemical indicators of changes in the nervous system.

The authors conducted a laboratory immunological examination of the secondary medical staff of the therapeutic profile and the comparison group. Using enzyme immunoassay in blood serum, the authors determined IgG class antibodies to nervous tissue proteins and the content of proinflammatory cytokines (IL-1β, IL-6, IL-8, TNF-α, IL-4).

In medical workers working under occupational stress, when compared with the comparison group, the authors revealed increased levels of AВ to nervous tissue proteins (S-100, Hol-R, GABA-R, DA-R, Ser-R), a change in cytokine balance characterized by hyperactivation of the proinflammatory immune response (IL-1β, IL-8) against the background of increased individual immunoreactivity in 75% of cases. Correlation analysis showed the presence of a relationship between AB to DA and IL-1β receptors.

The results obtained indicate a more likely risk of developing neuroimmune inflammation in medical staff and allow us to identify the most informative biomarkers (AT to DA-R, IL-1β, IL-8) for diagnosing disorders in the nervous system.

Limitations. The disadvantage of this work is the small number of employees.

Ethics. The study was conducted in compliance with ethical standards in accordance with the Helsinki Declaration of the World Medical Association. The work was approved by the local Ethics committee of the East-Siberian Institute of Medical and Ecological Research (Protocol No. 5 dated 03/21/2023).

Contributions:
Boklazhenko E.V. — research concept and design, data collection and processing, text writing;
Bodienkova G.M. — research concept and design, text writing, editing.

Funding. The work was carried out at the expense of financial resources allocated within the framework of the State Assignment of the East-Siberian Institute of Medical and Ecological Research.

Conflict of interest. The authors declare no conflict of interest.

Received: 19.02.2025 / Accepted: 20.02.2025 / Published: 07.04.2025

1. Matyushkina E.Ya., Roy A.P., Rakhmanina A.A., Kholmogorova A.B. Occupational stress and burnout among healthcare professionals. Sovremennaya zarubezhnaya psikhologiya [Journal of Modern Foreign Psychology]. 2020; 75(1): 57–79. https://doi.org/10.1080/17843286.2019.1699690 (in Russian)

2. Kobiakova O.S., Deev I.A., Kulikov E.S., Khomiakov K.V., Tiufilin D.S., Zagromova T.A. et al. The factors associated with development of professional burning-out in physicians. Problemi socialnoi gigieni, zdravookhranenia i istorii meditsini [Problems of Social Hygiene, Public Health and History of Medicine]. 2019; 27(6): 967–971 https://doi.org/10.32687/0869-866X-2019-27-6-967-971 (in Russian).

3. Lacy B.E., Chan J.L. Physician Burnout: The Hidden Health Care Crisis. Clin Gastroenterol Hepatol. 2018; 16(3): 311–317. https://doi.org/10.1016/j.cgh.2017.06.043

4. Verougstraete D., Hachimi Idrissi S. The impact of burn-out on emergency physicians and emergency medicine residents: a systematic review. Acta Clin. Belg. 2020; 75(1): 57–79. https://doi.org/10.1080/17843286.2019.1699690

5. Khalfin R.A., Smolnikova P.S., Stolkova A.S. Burnout among health care workers: a pressing problem for health care management. Natsional'noe zdravookhranenie [National Health Care]. 2023; 4(2): 40–46 https://doi.org/10.47093/2713-069X.2023.4.2.40-46 (in Russian)

6. Kobiakova O.S., Deev I.A., Kulikov E.S., Tyufilin D.S., Pleshkov M.O., Homyakov K.V. et al. The medical nurses: the factors of professional burning-out. Problemi socialnoi gigieni, zdravookhranenia i istorii meditsini [Problems of Social Hygiene, Public Health and History of Medicine]. 2021; 29(2): 353–358 https://doi.org/10.32687/0869-866X-2021-29-2-353-358 (in Russian).

7. Chepurnova N.S., Birko O.N., Knysh S.V., Rudneva A.V., Zharskaya V.V., Peskova A.E. i dr. Indicators of the cytokine system in practically healthy women of different ages and interrelation with the emotional state. Meditsinskaya Immunologiya [Medical Immunology]. 2023; 25(4): 735–740 https://doi.org/10.15789/1563-0625-IOT-2712 (in Russian).

8. Myagkova M.A., Morozova V.S., Petrochenko S.N. Natural autoantibodies in normal and pathological conditions. Immunopatologiya, allergologiya, infektologiya [Immunopathology, Allergology, Infectology]. 2016; (1): 20–26 https://doi.org/10.15789/1563-0625-IOT-2712 (in Russian).

9. Prokhorenko I.O., Germanova V.N., Sergeev O.S. Stress and the state of the immune system in normal and pathological conditions. Brief literature review. Vestnik meditsinskogo instituta «REAVIZ». Reabilitatsiya, Vrach i Zdorov′ye [Bulletin of the Medical Institute "REAVIZ" (Rehabilitation, Doctor and Health)]. 2017; 1(25): 82–90 (in Russian)

10. García-Bueno B., Caso J.R., Leza J.C. Stress as a neuroinflammatory condition in brain: damaging and protective mechanisms. Neurosci Biobehav Rev. 2008; 32(6): 1136–51. https://doi.org/0.1016/j.neubiorev.2008.04.001

11. Mathieu P., Battista D., Depino A., Roca V., Graciarena M., Pitossi F. The more you have, the less you get: the functional role of inflammation on neuronal differentiation of endogenous and transplanted neural stem cells in the adult brain. J. Neurochem. 2010; 112(6): 1368–85. https://doi.org/10.1111/j.1471-4159.2009.06548.x

12. Kuleshova M.V., Pankov V.A. Psychoemotional state during the formation of emotional burnout syndrome in middle-grade medical staff. Gigiena i sanitariya [Hygiene and Sanitation]. 2023; 102(8): 830–835 https://doi.org/10.47470/0016-9900-2023-102-8-830-835 (in Russian).

13. Poletaev A.B., Churilov L.P., Stroev Y.I., Agapov M.M. Immunophysiology versus immunopathology: natural autoimmunity in human health and disease. Pathophysiology. 2012; 19(3): 221–231. https://doi.org/10.1016/j.pathophys.2012.07.003

14. Poletaev A.B. Fiziologicheskaya immunologiya — estestvennye autoantitela i problemy nanomeditsiny [Physiological immunology — natural autoantibodies and problems of nanomedicine]. Moscow: Miklosh; 2011 (in Russian).

15. Kashtalyan OA, Ushakova LYu. Cytokines as universal regulation system. Meditsinskie novosti [Medical News]. 2017; (9): 3–7 (in Russian).

16. Spiridonova N., Basina E., Shchukin V. Natural (physiological) autoantibodies and regulation of homeostasis. Izvestiya Samarskogo nauchnogo centra RAN [News of Samara Scientific Center of the Russian Academy of Sciences]. 2015; 17(5-3): 861–867 (in Russian).

17. Kirschstein T., Köhling R. Functional changes in neuronal circuits due to antibody-driven autoimmune response. Neurobiol Dis. 2023; 184: 106221. https://doi.org/10.1016/j.nbd.2023.106221

18. Miteva D., Vasilev G.V., Velikova T. Role of Specific Autoantibodies in Neurodegenerative Diseases: Pathogenic Antibodies or Promising Biomarkers for Diagnosis. Antibodies (Basel). 2023; 12(4): 81. https://doi.org/10.3390/antib12040081

19. Tokarev A.R. Neuro-cytokine mechanisms of acute stress (Literature review). Vestnik novykh meditsinskikh tekhnologiy. Elektronnoe izdanie [Journal of new medical technologies, eEdition]. 2019; (3): 194-204. http://medtsu.tula.ru/VNMT/Bulletin/E2019-3/e2019-3.pdf https://doi.org/10.24411/2075-4094-2019-16469 (in Russian).

20. Lisitsyna T.A., Veltishchev D.Yu., Lila A.M., Nasonov E.L. Interleukin 6 as a pathogenetic factor mediating the formation of clinical manifestations and a target for the treatment of rheumatic diseases and depressive disorders. Nauchno-prakticheskaya revmatologiya [Rheumatology Science and Practice]. 2019; 57(3): 318-327 https://doi.org/10.14412/1995-4484-2019-318-327 (in Russian).