Genetic predictors of cytokine response in ENT-associated encephalitis

Author:

Kravtsov V. V.1,Shnayder N. A.2,Neznanov N. G.1,Krivopalov A. A.3,Yanov Y. K.3,Nasyrova R. F.1,Shamkina P. A.3,Gavrilyuk O. A.4

Affiliation:

1. V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology

2. V.M. Bekhterev National Medical Research Centre for Psychiatry and Neurology; V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

3. St.Petersburg Research Institute of Ear, Nose, Throat, and Speech

4. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University

Abstract

(1) Introduction: An imbalance of the genetically determined cytokine response plays a key role in the etiology of ENT-associated encephalitis. In recent years, an attempt has been made to evaluatethe prognostic role of chronic pathology of the paranasal sinuses in the development of acute, subacute and chronic encephalitis and meningitis, which in clinical practice are manifested both as cerebral and focal neurological symptoms and as mental disorders: from borderline to psychotic ones. The problem requires a multidisciplinary approach on the part of the specialists in the following clinical disciplines: neurology (as well as neurobiology), psychiatry, immunology, experimental medicine, otorhinolaryngology, and pharmacogenetics. The solution of this problem is possible with the involvement of preventive and personalized medicine.(2) The purpose: Evaluation the prognostic role of genetic polymorphisms of pro- and antiinflammatory cytokines in the development of ENT-associated encephalitis.(3) Materials and Methods: We conducted a keyword-based analysis of the English and Russian-language articles published within the past 30 years (from 1988 to 2018). The following databases were used in the study: PubMed, MedLine, Web of Science Core Collection (Clarivate Analytics), Web Science, Russian Science Citation Index, Scopus, Scientific Research, Google Scholar, Oxford Press, and eLibrary.(4) Results: In a number of the analyzed works, regardless of the causative agent and viral load, an increased level of pro-inflammatory cytokine production was noted in patients with more severe disease progression, neurological complications and unfavorable outcomes, both in viral encephalitis and in bacterial one. Based on this, 30 single nucleotide variants (SNV), their influence on the expression of pro- and anti-inflammatory cytokine genes, as well as their predictor role in the development of ENT-associated encephalitis were analyzed. Due to the nature of the systemic immune response, the analysis included both cerebral and extracerebral pathology-associated SNV. The inconsistency of the previously obtained results was noted, an attempt to explain this phenomenon was made. The analysis of the dynamics and geography of publications on the stated topic was made, the leading Russian scientific centers in the field were defined. The most promising SNV for further studies were identified.(5) Conclusion: The risk of developing ENT-associated encephalitis is associated with a genetically determined status of the cytokine response and its regulation. Studies of the association of various SNV of genes encoding pro- and anti-inflammatory cytokines in the Russian Federation need to be continued.

Publisher

V.M. Bekhterev National Research Medical Center for Psychiatry and Neurology

Reference141 articles.

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2. Beule, A. Epidemiology of chronic rhinosinusitis, selected risk factors, comorbidities, and economic burden. GMS current topics in otorhinolaryngology, head and neck surgery 2015, 14, Doc11 doi: 10.3205/cto000126. PMID: 26770285.

3. Krivopalov, A.A., Yanov, Yu.K., Scherbuk, A.U., Scherbuk, Yu.A., et al. Intracranial inflammatory complications of acute and chronic diseases of the ear, nose, and paranasal sinuses. SPb.: St. Petersburg, 2018. ISBN 978-5-9906975-6-0.

4. Fukumoto, Y., Okumura, A., Hayakawa, F., Suzuki, M., Kato, T., Watanabe, K., Morishima, T. Serum levels of cytokines and EEG findings in children with influenza associated with mild neurological complications. Brain and Development 2007, 29(7), 425-430. doi:10.1016/j.braindev.2006.12.005. PMID: 17287101.

5. Kombogiorgas, D., Seth, R., Athwal, R., Modha, J., Singh, J. Suppurative intracranial complications of sinusitis in adolescence. Single institute experience and review of literature. British Journal of Neurosurgery 2007, 21(6), 603-609. doi:10.1080/02688690701552856.

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