CHARACTERISTICS OF CELLULAR COMPARTMENT CHANGES OF IMMUNE SYSTEM IN THE PATIENTS WITH CHRONIC POLYPOUS RHINOSINUSITIS DEPEND ON EFFICIENCY OF DRUG THERAPY
https://doi.org/10.15789/1563-0625-2019-4-715-724
Abstract
Despite numerous attempts to control the course of chronic rhinosinusitis with nasal polyps (CRSwNP) by means of pharmacological treatment and new surgical approaches, the majority of patients experience lifelong persistence of this disorder, at recurrence rates of 50-60% within 18 months after surgical treatment. Since CRSwNP is a chronic persistent inflammatory process, it affects the entire body condition, including the state of systemic immune response. An elevation of NK (CD3-CD16+CD56+), activated NK (CD8+CD3-), NKT cells (CD16+CD56+CD3+), Treg (CD4+CD25brightCD127low to neg) cells and activated T-lymphocytes (CD3+CD25+) was revealed elsewhere among all the patients with CRSwNP, using a flow ytometry method. There was no difference between various disease phenotypes. We analyzed the status of cellular component of systemic immunity, dependent on clinical course of the disease and efficiency of the administered therapy of CRSwNP. The patients were divided into three subgroups. The follow-up period was 1 year. The first group comprised the patients who showed positive dynamics after conservative therapy, resulting into regression of nasal polyps and their grade than a year ago. The second group included the patients in whom the size of polyps remained the same. The third group included the patients with higher incidence of nasal polyps than a year ago.
We have shown a decrease of Treg, NKT cells, NK and activated NK, cytotoxic T-lymphocytes (CD3+CD8+), activated T-cell numbers in clinical group 3 with aggressive growth of polyps and low effect of standard therapy, which may cause deterioration of the immune system cellular populations, accompanied by presence of persistent productive inflammatory process of nasal cavity and paranasal sinuses. In the second group, a significant elevation of total lymphocyte number, total and activated T cells, T helpers (CD3+CD4+), cytotoxic T lymphocytes, NK and NKT cells was shown. Meanwhile, a decrease in absolute number of activated NK was observed despite the NK growth. Therefore, we can assume that the mechanism of their activation was disturbed and compensated by production of NKT cells and cytotoxic T lymphocytes. Moreover, we have shown in this group that the absolute number of Treg cells is increased; and these cells had a suppressive influence on effector cells of adaptive immune response, thus inducing incomplete elimination of infectious agents, which contribute to permanent incomplete course of inflammatory process. Chronic inflammatory process in CRSwNP affects systemic cellular immunity depending on the morbidity characteristics in the course of pathological process. The maximal intensity of systemic cellular immunity is observed in the group of patients that require permanent basic drug therapy. In case of aggressive CRSwNP and failure of standard drug therapy, we observed a decrease in absolute numbers of effector cells, along with decreased Treg lymphocyte numbers which may explain inefficient immune regulation of inflammatory process and medical interventions in this group of patients.
About the Authors
E. L. SavlevichRussian Federation
PhD (Medicine), Associate Professor, Department of Otorhinolaryngology
121359, Russian Federation, Moscow, M. Timoshenko str., 19, bldg 1A
Phone: 7 (985) 145-27-45
Fax: 7 (499) 140-20-78
A. V. Zurochka
Russian Federation
PhD, MD (Medicine), Professor, Leading Research Associate, Laboratory of Inflammatory Immunology; Professor, Department
of Food Technology and Biotechnology
Ekaterinburg
Chelyabinsk
S. V. Khaidukov
Russian Federation
S.V., PhD, MD (Biology), Senior Research Associate, Scientific and Innovation Center Technopark Division
Moscow
References
1. Artyushkin S.A. Comparative estimation of influence chronic polypose rhinosinusinysitis and malignant diseases on reactivity of blood circulation. Russian otorhinolaryngology. 2010;46 (3):205-210. (in Russ)
2. Zurochka A.V., Semenov M.V., Zurochka V.A., Khaidukov S.V. Study of immune system parameters and T-regulatory cells level at the patients suffering polypoid rhinosinusitis. Russian Journal of Immunology. 2011;5(14): 280-285. (in Russ)
3. Zurochka A.V., Khaidukov S.V., Kudryavtsev I.V., Chereshnev V.A. Flow cytometry in biomedical research. Ekaterinburg: RIO UrO RAN, 2018. 720 p.
4. Savlevich EL, Kozlov VS, Kurbacheva OM. The modern trends in the diagnostic search for and the treatment of chronic rhinosinusitis with nasal polyps. Rossiyskaya rinologiya. 2018;26(2),3-4:41-47. (in Russ)
5. Savlevich E.L., Kurbacheva O.M., Khaidukov S.V., Gerasimov A.N., Amanturlieva M.E., Simbirtcev A.S. The diagnostic significance of immunological parameters of the patients with chronic rhinosinusitis with nasal polyps. Russian allergology journal. 2017;4/5:40-45. (in Russ)
6. Savlevich EL, Kurbacheva OM, Shachnev KN. The expediency of the application of the immunomodulatory medications for the treatment of chronic rhinosinusitis with nasal polyps. Rossiyskaya rinologiya. 2018;26(3): 41-46. (in Russ)
7. Savlevich E.L., Khaidukov S.V., Kurbacheva O.М., Bondareva G.P., Shachnev K.N., Simbirtsev A.S. Characteristics of cellular immune status in the patients with chronic rhinosinusitis with nasal polyps. Medical Immunology (Russia). 2017;19(6):731-738. (In Russ.)
8. Semenov M.V., Zurochka A.V., Zurochka V.A. Quantitative changes of T-regulatory cells in patients with polipous rhinosinusitis treated by nasal glucocorticosteroids. Medical Immunology (Russia). 2012;14(3):233-238. (In Russ.)
9. Khaidukov S.V., Zurochka A.V., Totolian Areg A., Chereshnev V.A. Major and lymphocyte populations of human peripheral blood lymphocytes and their reference values, as assayed by multi-colour cytometry. Medical Immunology (Russia). 2009;11(2-3):227-238.
10. Bachert C, Zhang N, Hellings PW, Bousquet J. Endotype-driven care pathways in patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2018;141(5):1543-1551.
11. DeConde AS, Mace JC, Levy JM, Rudmik L, Alt JA, Smith TL. Prevalence of polyp recurrence after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyposis. Laryngoscope. 2017;127(3):550-555.
12. Dennis S.K, Lam K, Luong A. A review of classification schemes for chronic rhinosinusitis with nasal polyposis endotypes. Laryngoscope Investig Otolaryngol. 2016;1(5):130-134.
13. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F, Cohen N, Cervin A, Douglas R, Gevaert P, Georgalas C, Goossens H, Harvey R, Hellings P, Hopkins C, Jones N, Joos G, Kalogjera L, Kern B, Kowalski M, Price D, Riechelmann H, Schlosser R, Senior B, Thomas M, Toskala E, Voegels R, Wang de Y, Wormald PJ. European position paper on rhinosinusitis and nasal polyps 2012. Rhinol Suppl. 2012;50(23):1-298.
14. Gurrola J, Borish L. Chronic rhinosinusitis: Endotypes, biomarkers, and treatment response. 2017;140(6):1499-1508.
15. Hellings PW, Fokkens WJ, Bachert C, Akdis CA, Bieber T, Agache I, Bernal-Sprekelsen M, Canonica GW, Gevaert P, Joos G, Lund V, Muraro A, Onerci M, Zuberbier T, Pugin B, Seys SF, Bousquet J; ARIA and EPOS working groups. Positioning the principles of precision medicine in care pathways for allergic rhinitis and chronic rhinosinusitis - A EUFOREA-ARIA-EPOS-AIRWAYS ICP statement. Allergy. 2017 Sep;72(9):1297-1305.
16. Rudmik L, Soler ZM, Mace JC, Schlosser RJ, Smith TL. Economic evaluation of endoscopic sinus surgery versus continued medical therapy for refractory chronic rhinosinusitis. Laryngoscope. 2015; 125(1): 25–32.
17. Senior BA, Glaze C, Benninger MS. Use of the Rhinosinusitis Disability Index (RSDI) in rhinologic disease. Senior BA1, Glaze C, Benninger MS. Am J Rhinol. 2001;15(1):15-20.
18. Stevens WW, Peters AT, Hirsch AG, Nordberg CM, Schwartz BS, Mercer DG, Mahdavinia M, Grammer LC, Hulse KE, Kern RC, Avila P, Schleimer RP Clinical Characteristics of patients with chronic rhinosinusitis with nasal polyps, asthma, and aspirin-exacerbated respiratory disease. J Allergy Clin Immunol Pract. 2017;5(4):1061-1070.
19. Tosun F, Arslan HH, Karslioglu Y, Deveci MS, Durmaz A. Relationship between postoperative recurrence rate and eosinophil density of nasal polyps. Ann Otol Rhinol Laryngol. 2010;119(7):455–459.
20. Van Zele T, Holtappels G, Gevaert P, Bachert C. Differences in initial immunoprofiles between recurrent and nonrecurrent chronic rhinosinusitis with nasal polyps. Am J Rhinol Allergy. 2014;28(3):192-198.
Review
For citations:
Savlevich E.L., Zurochka A.V., Khaidukov S.V. CHARACTERISTICS OF CELLULAR COMPARTMENT CHANGES OF IMMUNE SYSTEM IN THE PATIENTS WITH CHRONIC POLYPOUS RHINOSINUSITIS DEPEND ON EFFICIENCY OF DRUG THERAPY. Medical Immunology (Russia). 2019;21(4):715-724. (In Russ.) https://doi.org/10.15789/1563-0625-2019-4-715-724