IMMUNOLOGICAL MARKERS OF UNCONTROLLED ATOPIC BRONCHIAL ASTHMA IN CHILDREN
https://doi.org/10.15789/1563-0625-2017-4-453-460
Abstract
Bronchial asthma is a prevalent chronic allergic disease of lungs at early ages. A priority task in allergology is to search biological markers related to uncontrolled atopic bronchial asthma. Cytokines fulfill their distinct function in pathogenesis of atopic bronchial asthma, participating at the initiation, development and persistence of allergic inflammation in airways, causing different variations of clinical course of the disease (with respect to its acuteness, severity, frequency of exacerbations). The present work has studied indices of cellular and humoral links of immunity, as well as levels of some pro and anti-inflammatory cytokines in peripheral blood serum (IL-4, IL-10, IL-2 and TNFα), aiming to determine potential markers of uncontrolled atopic bronchial asthma in children. A group of Caucasian (European) children was involved into the research: Cohort 1, moderate atopic bronchial asthma with controlled course during the last 3 months (n = 59); Cohort 2, severe/moderate-severe atopic bronchial asthma with uncontrolled course of the disease within last 3 months (n = 51), Cohort 3 – control, practically healthy children without signs of atopy (n = 33). All the children included in the group with atopic bronchial asthma underwent regular mono/combined basic therapy at high/ intermediate therapeutic doses. We performed a comparative analysis of cell population indices reflecting certain cellular immunity links, and determined significantly lower levels of CD3+ lymphocytes, as well as decrease in relative and absolute contents of CD4+ and CD8+ cells in the cohort with uncontrolled course of atopic bronchial asthma, as compared with controlled-course cohort. When evaluating concentrations of cytokines in peripheral blood serum of the patients with controlled and uncontrolled atopic bronchial asthma, we revealed significantly higher levels of IL-2, IL-4, and IL-10, as compared to control group. It was found that TNFα concentration is considerably higher in both cohorts of the patients, being 2to 3-fold higher than the levels of this cytokine in control group. When comparing the cohorts with different control of the disease course, we have found that TNFα concentration in the cohort with uncontrolled bronchial asthma is statistically higher than among children with controllable course of the disease. Hence, the following parameters may serve as potential markers of pediatric atopic bronchial asthma with uncontrolled course: low levels of total Т lymphocyte numbers in peripheral blood, and decreased counts of CD4+, CD8+ cells; IgE hyperproduction; low contents of common IgA, and high concentration of TNFα in peripheral blood serum.
About the Authors
M. V. SmolnikovaRussian Federation
Smolnikova Marina V. - PhD (Biology), Leading Research Associate, SRIMPN, FRC KSC SB RAS; KS V.F. Voino-Yasenetsky MU, Krasnoyarsk, Russian Federation
660022, Krasnoyarsk, Partizan Zeleznyak str., 3g. Phone/Fax: 7 (391) 228-06-83
S. V. Smirnova
Russian Federation
PhD, MD (Medicine), Professor, Head of Scientific Direction, SRIMPN, FRC KSC SB RAS; KS V.F. Voino-Yasenetsky MU
N. A. Ilyenkova
Russian Federation
PhD, MD (Medicine), Professor, Head, Department of Pediatric Diseases with a PE course KS V.F. Voino-Yasenetsky MU
O. S. Konopleva
Russian Federation
PhD (Medicine), Junior Research Associate, SRIMPN, FRC KSC SB RAS; KS V.F. Voino-Yasenetsky MU
References
1. Архипов В.В. Новые перспективы повышения контроля над бронхиальной астмой. От науки к практике // Практическая пульмонология, 2014. № 1. С. 67-76. [Arkhipov V.V. New prospects for increasing control over bronchial asthma. From science to practice. Prakticheskaya pulmonologiya = Practical Pulmonology, 2014, no. 1, pp. 67-76. (In Russ.)]
2. Барабаш Е.Ю., Калинина Е.П., Гвозденко Т.А., Денисенко Ю.К., Новгородцева Т.П., Антонюк М.В., Ходосова К.К. Регуляция иммунного ответа у пациентов с частично контролируемой и контролируемой бронхиальной астмой // Медицинская иммунология, 2017. Т. 19, № 1. С. 65-72. [Barabash E.Yu., Kalinina E.P., Gvozdenko T.A., Denisenko Yu.K., Novgorodtseva T.P., Antonyuk M.V., Khodosova K.K. Regulation of the immune response in patients with partially controlled and controlled bronchial asthma. Meditsinskaya immunologiya = Medical Immunology (Russia), 2017, Vol. 19, no. 1, pp. 65-72. (In Russ.)] doi: 10.15789/1563-0625-2017-1-65-72.
3. Гурьева Л.Л. Сывороточное содержание иммунорегуляторных цитокинов у детей, больных атопической бронхиальной астмой с разной степенью контроля над заболеванием // Медицинский вестник Башкортостана, 2014. Т. 9, № 3. С. 61-65. [Gurieva L.L. Serum content of immunoregulatory cytokines in children with atopic bronchial asthma with varying degrees of control over the disease. Meditsinskiy vestnik Bashkortostana = Medical Bulletin of Bashkortostan, 2014, Vol. 9, no. 3, pp. 61-65. (In Russ.)]
4. Горячкина Л., Кашкин К. Клиническая аллергология и иммунология. М.: Миклош, 2009. 432 с. [Goryachkina L., Kashin K. Clinical allergology and immunology]. Moscow: Miklosh, 2009. 432 p.
5. Кайб И.Д., Петрушина А.Д., Никогосян А.С., Шайтарова А.В., Мальченко Л.А. Иванова Е.Е. Патогенетические аспекты воспаления при бронхиальной астме у детей дошкольного возраста // Медицинская наука и образование Урала, 2016. № 4. С. 80-82. [Kayb I.D.,Petrushina A.D., Nikoghosyan A.S., Shaytarova A.V., Malchenko L.A., Ivanova E.E. Pathogenetic aspects of inflammation in bronchial asthma in preschool children. Meditsinskaya nauka i obrazovanie Urala = Medical Science and Education of the Urals, 2016, no. 4, pp. 80-82. (In Russ.)]
6. Кетлинский С.А., Симбирцев А.С. Цитокины. СПб.: Фолиант, 2008. 552 с. [Ketlinskiy S.A., Simbirtsev A.S. Cytokines]. St. Petersburg: Folio, 2008. 552 p.
7. Намазова–Баранова Л.С. Аллергия у детей: от теории к практике. М.: Союз педиатров России, 2011. 668 с. [Namazova-Baranova L.S. Allergy in children: from theory to practice]. Moscow: Union of Pediatricians of Russia, 2011. 668 p.
8. Смольникова М.В., Смирнова С.В., Коноплева О.С. Цитокины и полиморфизм промоторных регионов генов (C-590T IL4, C-597A IL10) как маркеры неконтролируемого течения бронхиальной астмы у детей // Сибирский научный медицинский журнал, 2015. Т. 35, № 3. С. 4-8. [Smolnikova M.V., Smirnova S.V., Konopleva O.S. Cytokines and polymorphism of promoter regions of genes (C-590T IL4, C-597A IL10) as markers of uncontrolled flow of bronchial asthma in children. Sibirskiy nauchnyy meditsinskiy zhurnal = Siberian Scientific Medical Journal, 2015, Vol. 35, no. 3, pp. 4-8. (In Russ.)]
9. Смольникова М.В., Смирнова С.В., Тютина О.С., Бычковская С.В. Полиморфизм генов цитокинов (IL4, IL10) и особенности иммунного реагирования в зависимости от уровня контроля над течением атопической бронхиальной астмы у детей // Российский аллергологический журнал, 2013. № 2. С. 23-28. [Smolnikova M.V., Smirnova S.V., Tyutina O.S., Bychkovskaya S.V. Polymorphism of genes of cytokines (IL-4, IL-10 and feauture of immune reaction depending on the level of control over the course of atopic bronchial asthma at children. Rossiyskiy allergologicheskiy zhurnal = Russian Allergology Journal, 2013, no. 2, pp. 23-28. (In Russ.)]
10. Al-Daghri N.M., Alokail M.S., Draz H.M., Abd-Alrahman S.H., Yakout S.M., Clerici M. Th1/Th2 cytokine pattern in Arab children with severe asthma. Clin. Exp. Allergy, 2014, Vol. 44, no. 2, pp. 222-230.
11. Brown S.D., Brown L.A., Stephenson S., Dodds J.C., Douglas S.L., Qu H., Fitzpatrick A.M. Characterization of a high TNFα phenotype in children with moderate-to-severe asthma. J. Allergy Clin. Immunol., 2015, Vol. 135, no. 6, рр. 1651-1654.
12. Brzozowska A., Majak P., Jerzyńska J., Smejda K., Bobrowska-Korzeniowska M., Stelmach W., Koczkowska M., Stelmach I. Exhaled nitric oxide correlates with IL-2, MCP-1, PDGF-BB and TIMP-2 in exhaled breath condensate of children with refractory asthma. Postepy Dermatol. Alergol., 2015, Vol. 32, no. 2, pp. 107-113.
13. Carlier F.M., Sibille Y., Pilette C. The epithelial barrier and immunoglobulin A system in allergy. Clin. Exp. Allergy, 2016, Vol. 46, no. 11, pp. 1372-1388.
14. Chkhaidze I., Zirakishvili D., Shavshvishvili N., Barnabishvili N. Prognostic value of TH1/TH2 in infants with wheezing in a three year follow-up study. Pneumonol. Alergol. Pol., 2016, Vol. 84, no 3, pp. 144-150.
15. Cui A.H., Zhao J., Liu S.X., Hao Y.S. Associations of IL-4, IL-6, and IL-12 levels in peripheral blood with lung function, cellular immune function, and quality of life in children with moderate-to-severe asthma. Int. J. Clin. Exp. Med., 2014, Vol. 15, no. 7 (8), pp. 2286-2291.
16. Giovannini-Chami L., Albertini M., Scheinmann P., de Blic J. New insights into the treatment of severe asthma in children. Paediatric Respiratory Reviews, 2015, Vol. 16, no. 3, рр. 167-173.
17. Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA). Update 2015 // http://www.ginasthma.org
18. Irvin C., Zafar I., Good J., Rollins D., Christianson C., Gorska M.M., Martin R.J., Alam R. Increased frequency of dual-positive TH2/TH17 cells in bronchoalveolar lavage fluid characterizes a population of patients with severe asthma. J. Allergy Clin. Immunol., 2014, Vol. 134, no. 5, рр. 1175-1186.
19. Kim W.J., Choi I.S., Kim C.S., Lee J.H., Kang H.W. Relationship between serum IgA level and allergy/asthma. Korean J. Intern. Med., 2017, Vol. 32, no. 1, pp. 137-145.
20. Lama M., Chatterjee M., Chaudhuri T.K. Total serum immunoglobulin Е in children with asthma. Pediatr. Pulmonol., 2013, Vol. 48, no. 11, pp. 1062-1069.
21. Michaud B., Gouvis-Echraghi R., Candon S., Couderc R., Jais J.P., Bach J.F., Chatenoud L., Just J. Quantification of circulating house dust mite-specific IL-4and IL-13-secreting T cells correlates with rhinitis severity in asthmatic children and varies with the seasons. Indian J. Clin. Biochem., 2013, Vol. 28, no. 2, pp. 197-200.
22. Smirnova S., Smolnikova M., Tereshchenko S. Immune response and polymorphism of the cytokine genes (IL4, IL10 and IL2, TNFA) in atopic bronchial asthma in Russian children. Allergy, 2014, Vol. 69, p. 227 (551).
23. Smolnikova M.V., Smirnova S.V., Freidin M.B., Tyutina O.S. Immunological parameters and gene polymorphisms (C-590T IL4, C-597A IL10) in severe bronchial asthma in children from the Krasnoyarsk region. West Siberia J. Circumpolar. Health., 2013, Vol. 5, p. 72.
24. Tomiita M., Campos-Alberto E., Shima M., Namiki M., Sugimoto K., Kojima H., Watanabe H., Sekine K., Nishimuta T., Kohno Y., Shimojo N. Interleukin-10 and interleukin-5 balance in patients with active asthma, those in remission, and healthy controls. Postepy Dermatol. Allergol., 2015, Vol. 32, no. 2, pp. 107-113.
25. Vizmanos-Lamotte G., Moreno A., Munoz X., Gomez S., Gartner S., Cruz M.J. Induced sputum cell count and cytokine profile in atopic and non-atopic children with asthma. Asia Pac. Allergy, 2015, Vol. 5, no. 4, pp. 210-215.
Review
For citations:
Smolnikova M.V., Smirnova S.V., Ilyenkova N.A., Konopleva O.S. IMMUNOLOGICAL MARKERS OF UNCONTROLLED ATOPIC BRONCHIAL ASTHMA IN CHILDREN. Medical Immunology (Russia). 2017;19(4):453-460. (In Russ.) https://doi.org/10.15789/1563-0625-2017-4-453-460