pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2021-31-1-46-56pulmo-2265Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESФеномен аутореактивности в патогенезе сочетания бронхиальной астмы и хронической обструктивной болезни легкихThe autoreactivity phenomenon in the pathogenesis of asthma-COPD overlap (ACO)КонищеваА. Ю.KonishchevaA. Yu.

Конищева Анна Юрьевна - кандидат медицинских наук, ведущий научный сотрудник лаборатории аллергодиагностики.105064, Москва, Малый Казенный переулок, 5а.тел.: (495) 917-86-51

Anna Yu. Konishcheva - Candidate of Medicine, Leading Researcher, Allergy Diagnosis Department, I.I.Mechnikov Research Institute of Vaccines and Sera.105064, Matyy Kazennjy per. 5a, Moscow, 105064.tel.: (495) 917-86-51

ankon81@list.ruГервазиеваВ. Б.GervazievaV. B.

Гервазиева Валентина Борисовна - доктор медицинских наук, профессор, заведующая лабораторией аллергодиагностики, заведующая отделом аллергологии.105064, Москва, Малый Казенный переулок, 5а.тел.: (495) 917-20-26

Valentina B. Gervazieva - Doctor of Medicine, Professor, Head of Allergy Diagnosis Department, I.I.Mechnikov Research Institute of Vaccines and Sera.105064, Matyy Kazennjy per. 5a, Moscow, 105064.tel.: (495) 917-20-26

vbger@mail.ruОсиповаГ. Л.OsipovaG. L.

Осипова Галина Леонидовна, - доктор медицинских наук, профессор, заведующая отделением клинических исследований.115682, Москва, Ореховый бульвар, 28.тел.: (495) 395-63-93

Galina L. Osipova - Doctor of Medicine, Professor, Head of Division of Clinical Trials, Federal Pulmonology Research Institute, Federal Medical and Biological Agency of Russia.Orekhovyy bul'var 28, Moscow, 115682.tel.: (495) 395-63-93

osipovagl@mail.ruОспельниковаТ. П.Ospel'nikovaT. P.

Оспельникова Татьяна Петровна - кандидат медицинских наук, заведующая лабораторией интерферонов.105064, Москва, Малый Казенный переулок, 5а.тел: (495) 917-35-81

Tat'yana P. Ospel'nikova - Candidate of Medicine, Head of the laboratory of interferons I.I.Mechnikov Research Institute of Vaccines and Sera.105064, Matyy Kazennjy per. 5a, Moscow, 105064.tel.: (495) 91735-81

ospelnikovat@mail.ruНаучно-исследовательский институт вакцин и сывороток имени И.И.МечниковаРоссияI.I. Mechnikov Research Institute of Vaccines and SeraRussian FederationНаучно-исследовательский институт пульмонологии Федерального медико-биологического агентстваРоссияFederal Pulmonology Research Institute, Federal Medical and Biological Agency of RussiaRussian Federation2021190220213114656Copyright © Конищева А.Ю., Гервазиева В.Б., Осипова Г.Л., Оспельникова Т.П., 20212021Конищева А.Ю., Гервазиева В.Б., Осипова Г.Л., Оспельникова Т.П.Konishcheva A.Y., Gervazieva V.B., Osipova G.L., Ospel'nikova T.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/2265

Современная концепция формирования бронхиальной астмы (БА) и хронической обструктивной болезни легких (ХОБЛ) предполагает ведущую роль иммуноопосредованных реакций с вовлечением как истинного воспалительного, так и аутоиммунного компонентов патогенеза. Целью исследования явилась оценка процессов аутореактивности у пациентов с хроническими заболеваниями органов дыхания (БА и ХОБЛ), а также при сочетании указанных патологий (Asthma-COPD Overlap - ACO). Материалы и методы. В исследование принимали участие пациенты (n = 155; средний возраст пациентов — 49 ± 17 лет) с БА, ХОБЛ и ACO. Исследование проводилось модифицированным методом количественного иммуноферментного анализа для детекции иммуноглобулина (Ig) E-, IgG4-аутоантител (ААТ) с использованием коммерческих тканевых антигенов (ТАГ) эпителиального кератина, коллагена III и VI типов, миозина и эластина (Sigma, США), конъюгатов моноклональных анти-IgE или анти-IgG4-антител, IgE- и IgG4-референс-реагентов (Dr. Fooke, Германия). Результаты. Показано, что при присоединении к БА симптомов ХОБЛ достоверно повышается содержание IgE-ААТ к ТАГ эпителиального кератина, коллагена III и VI типов и миозина, что ассоциировалось с высокой частотой выявления данных антител, особенно при тяжелом течении заболевания (50—80 %). Уровень IgE-ААТ к миозину возрастал у пациентов с ACO в сравнении с таковым при БА и составил максимальные значения у пациентов с ХОБЛ. Напротив, отмечена обратная тенденция снижения частоты встречаемости и концентрации IgG4-ААТ в зависимости от тяжести течения заболевания. Так, по мере выраженности обструктивных изменений отмечалось значимое снижение уровня IgG4-ААТ к коллагенам III и VI типов и эластину до исчезновения последних при ХОБЛ и АСО. Выявлена обратная корреляция (r = —0,38; —0,61) IgE- и IgG4-ААТ к коллагену VI и III типов, эластину и миозину. При сравнении спирометрических показателей установлена обратная корреляция между повышенным содержанием IgE-ААТ к ТАГ коллагена III типа и скоростными параметрами легочной вентиляции (R = —0,79; p = 0,01), что позволяет рассматривать данные IgE-ААТ как фактор прогрессирующего течения БА в сочетании с ХОБЛ, ассоциированного со значимым уровнем снижения бронхиальной проходимости. Заключение. Детекция IgE и IgG4-ААТ к ТАГ коллагена, эластина и миозина может быть использована для клинико-иммунологического мониторинга течения БА и ХОБЛ, особенно при сочетанном фенотипе данных заболеваний (АСО). Повышение уровня IgE-ААТ к ТАГ может служить одним из иммунологических маркеров выраженности процессов ремоделирования в бронхиальной стенке, что подтверждается показанным усилением IgE-опосредованного иммунного ответа к ТАГ миозина и эластина у пациентов с тяжелым течением заболевания. Разработанный метод оценки содержания ААТ к ТАГ может быть предложен в качестве одного из прогностических маркеров в ранней диагностике неблагоприятного течения БА, особенно при сочетании БА и ХОБЛ и использован в качестве лабораторного критерия контроля над течением заболевания при принятии индивидуализированных решений о фармакотерапии и тактике ведения пациентов.

The modern concept of development of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) implies the leading role of immune reactions with the true inflammatory autoimmune pathogenetic components. Aim of the study was to evaluate the autoreactivity in patients with chronic immune-mediated respiratory diseases: BA, COPD, and their combination — ACO. Methods. The study enrolled 155 patients with the average age of 49 ± 17 years old. We modified quantitative ELISA for detection of IgE and IgG4-autoantibodies using commercial tissue antigens of epithelial keratin, type III and VI collagen, myosin and elastin (Sigma, USA), conjugates of monoclonal anti-IgE or anti-IgG4 antibodies and IgE and IgG4 reference reagents (Dr. Fooke, Germany). Results. Concomitant COPD and BA symptoms were accompanied by significantly higher levels of IgE autoAbs to epithelial keratin, type III and VI collagen and myosin and were associated with a higher detection rate of these Abs, especially in severe forms of the disease (50 — 80%). The IgE-autoAbs to myosin increased in individuals with ACO as compared to BA and reached the maximum values in patients with COPD. There was an opposite trend: the frequency of detection and concentration of IgG4-autoAbs decreased with the disease severity. The levels of IgG4-autoAbs to type III and IV collagens and to elastin decreased as the obstruction worsened and were undetectable in patients with COPD and ACO. IgE and IgG4 autoAbs were inversely correlated to type VI collagen, type III collagen, elastin and myosin (r = -0.38; -0.61). The spirometry showed the inverse correlations between the increased IgE-autoAbs to type III collagen and high-speed ventilation parameters (R = -0.79; p = 0.01). So, IgE-autoAbs may be considered a factor of the progressive course of BA in combination with COPD associated with a significant bronchial obstruction. Conclusion. Thus, the detection of IgE and IgG4-AT to tissue antigens of collagen, elastin and myosin can be further used for clinical and immunological monitoring of BA and COPD, especially with their combined phenotype (ACO). The increased levels of IgE-autoAbs can be considered one of the immunological prognostic markers of intense remodeling processes in the bronchial wall. These processes are also confirmed by an increased IgE-mediated immune response to miosine and elastine EG in patients with the severe disease. The developed assay of the level of autoAbs to tissue antigens can be used in the early diagnostics of adverse course of asthma, especially ACO, and can be used as a laboratory criterion of the control over the disease when making decisions on personalized pharmacotherapy and patient management.

аутореактивностьIgE- и IgG4-аутоантителабронхиальная астма (БА)хроническая обструктивная болезнь легких (ХОБЛ)сочетание БА и ХОБЛкератинколлагены III и VI типовмиозинэластинаutoreactivityIgE- and IgG4-autoantibodiesbronchial asthmachronic obstructive pulmonary disease (COPD)asthma-COPD overlap (ACO)keratincollagens of types III and VImyosinelastinReferencesGBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017; 390 (10100): 1211-1259. DOI: 10.1016/S0140-6736(17)32154-2.GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990—2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017; 390 (10100): 1211—1259. DOI: 10.1016/S0140-6736(17)32154-2.Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by Region, 2000-2016. Geneva: World Health Organization; 2018.Global Health Estimates 2016: Deaths by Cause, Age, Sex, by Country and by Region, 2000—2016. Geneva: World Health Organization; 2018.Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2018. Available at: https://ginasthma.org/wp-content/uploads/2019/01/2018-GINA.pdfGlobal Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2018. Available at: https://ginasthma.org/wp-content/uploads/2019/01/2018-GINA.pdfChuchalin A.G., Khaltaev N., Antonov N.S. et al. Chronic respiratory diseases and risk factors in 12 regions of Russian Federation. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9 (1): 963-974. DOI: 10.2147/COPD.S67283.Chuchalin A.G., Khaltaev N., Antonov N.S. et al. Chronic respiratory diseases and risk factors in 12 regions of Russian Federation. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9 (1): 963—974. DOI: 10.2147/COPD.S67283.Bateman E.D., Reddel H.K., Eriksson G. et al. Overall asthma control: The relationship between current control and future risk. J. Allergy Clin. Immunol. 2010; 125 (3): 600-608.e6. DOI: 10.1016/j.jaci.2009.11.033.Bateman E.D., Reddel H.K., Eriksson G. et al. Overall asthma control: The relationship between current control and future risk. J. Allergy Clin. Immunol. 2010; 125 (3): 600—608.e6. DOI: 10.1016/j.jaci.2009.11.033.Чучалин А.Г., Айсанов З.Р., Авдеев С.Н. и др. Федеральные клинические рекомендации по диагностике и лечению хронической обструктивной болезни легких. Русский медицинский журнал. 2014; 22 (5): 331-346.Chuchalin A.G., Aisanov Z.R., Avdeev S.N. et al. [Federal clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease]. Russkiy meditsinskiy zhur-nal. 2014; 22 (5): 331—346 (in Russian).Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2018. Available at: http://goldcopd.org/Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2018. Available at: http://goldcopd.org/GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 2017; 5 (9): 691-706. DOI: 10.1016/S2213-2600(17)30293-X.GBD 2015 Chronic Respiratory Disease Collaborators. Global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990—2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir. Med. 2017; 5 (9): 691—706. DOI: 10.1016/S2213-2600(17)30293-X.Masoli M., Fabian D., Holt S., Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004; 59 (5): 469-478. DOI: 10.1111/j.1398-9995.2004.00526.x.Masoli M., Fabian D., Holt S., Beasley R. The global burden of asthma: executive summary of the GINA Dissemination Committee Report. Allergy. 2004; 59 (5): 469—478. DOI: 10.1111/j.1398-9995.2004.00526.x.Agache I., Strasser D.S., Pierlot G.M. et al. Monitoring inflammatory heterogeneity with multiple biomarkers for multidimensional endotyping of asthma. J. Allergy Clin. Immunol. 2018; 141 (1): 442-445. DOI: 10.1016/j.jaci.2017.08.027.Agache I., Strasser D.S., Pierlot G.M. et al. Monitoring inflammatory heterogeneity with multiple biomarkers for multidimensional endotyping of asthma. J. Allergy Clin. Immunol. 2018; 141 (1): 442—445. DOI: 10.1016/j.jaci.2017.08.027.Hollander Z., DeMarco M.L., Sadatsafavi M. et al. Biomarker development in COPD: moving from p values to products to impact patient care. Chest. 2017; 151 (2): 455-467. DOI: 10.1016/j.chest.2016.09.012.Hollander Z., DeMarco M.L., Sadatsafavi M. et al. Biomarker development in COPD: moving from p values to products to impact patient care. Chest. 2017; 151 (2): 455—467. DOI: 10.1016/j.chest.2016.09.012.Celli B.R., Locantore N., Tal-Singer R. et al. Emphysema and extrapulmonary tissue loss in COPD: a multi-organ loss of tissue phenotype. Eur. Respir. J. 2018; 51 (2): 1702146. DOI: 10.1183/13993003.02146-2017.Celli B.R., Locantore N., Tal-Singer R. et al. Emphysema and extrapulmonary tissue loss in COPD: a multi-organ loss of tissue phenotype. Eur. Respir. J. 2018; 51 (2): 1702146. DOI: 10.1183/13993003.02146-2017.Suzuki M., Makita H., Konno S. et al. Asthma-like features and clinical course of chronic obstructive pulmonary disease. An analysis from the Hokkaido COPD Cohort Study. Am. J. Respir. Crit. Care Med. 2016; 194 (11): 1358-1365. DOI: 10.1164/rccm.201602-0353OC.Suzuki M., Makita H., Konno S. et al. Asthma-like features and clinical course of chronic obstructive pulmonary disease. An analysis from the Hokkaido COPD Cohort Study. Am. J. Respir. Crit. Care Med. 2016; 194 (11): 1358—1365. DOI: 10.1164/rccm.201602-0353OC.Barnes N.C., Sharma R., Lettis S., Calverley P.M.A. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur. Respir. J. 2016, 47 (5): 1374-1382. DOI: 10.1183/13993003.01370-2015.Barnes N.C., Sharma R., Lettis S., Calverley P.M.A. Blood eosinophils as a marker of response to inhaled corticosteroids in COPD. Eur. Respir. J. 2016, 47 (5): 1374—1382. DOI: 10.1183/13993003.01370-2015.Wenzel S.E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 2012; 18 (5): 716-725. DOI: 10.1038/nm.2678.Wenzel S.E. Asthma phenotypes: the evolution from clinical to molecular approaches. Nat. Med. 2012; 18 (5): 716—725. DOI: 10.1038/nm.2678.Busse W.W., Banks-Schlegel S., Wenzel S.E. Pathophysiology of severe asthma. J. Allergy Clin. Immunol. 2000; 106 (6): 1033-1042. DOI: 10.1067/mai.2000.111307.Busse W.W., Banks-Schlegel S., Wenzel S.E. Pathophysiology of severe asthma. J. Allergy Clin. Immunol. 2000; 106 (6): 1033—1042. DOI: 10.1067/mai.2000.111307.Fahy J.V. Type 2 inflammation in asthma - present in most, absent in many. Nat. Rev. Immunol. 2015; 15 (1): 57-65. DOI: 10.1038/nri3786.Fahy J.V. Type 2 inflammation in asthma — present in most, absent in many. Nat. Rev. Immunol. 2015; 15 (1): 57—65. DOI: 10.1038/nri3786.Сочетание хронической обструктивной болезни легких и бронхиальной астмы: согласительный документ Испанского общества пульмонологов и торакальных хирургов. Пульмонология. 2013; (1): 13-19.[Chronic obstructive pulmonary disease associated with asthma. Consensus document of Spanish Society of Pulmonologists and Thoracic Surgeons (SEPAR)]. Pul'monologiya. 2013; (1): 13—19 (in Russian).Diagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and Asthma - COPD Overlap Syndrome (ACOS). Based on Global Strategy for Asthma Management and Prevention and Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2014. Available at: https://ginasthma.org/wp-content/uploads/2019/11/GINA_GOLD_ACOS_2014-wms.pdfDiagnosis of Diseases of Chronic Airflow Limitation: Asthma, COPD and Asthma — COPD Overlap Syndrome (ACOS). Based on Global Strategy for Asthma Management and Prevention and Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2014. Available at: https://ginasthma.org/wp-content/uploads/2019/11/GINA_GOLD_ACOS_2014-wms.pdfLouie S., Zeki A.A., Schivo M. et al. The asthma-chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic considerations. Expert Rev. Clin. Pharmacol. 2013; 6 (2): 197-219. DOI: 10.1586/ecp.13.2.Louie S., Zeki A.A., Schivo M. et al. The asthma—chronic obstructive pulmonary disease overlap syndrome: pharmacotherapeutic considerations. Expert Rev. Clin. Pharmacol. 2013; 6 (2): 197—219. DOI: 10.1586/ecp.13.2.Sin D.D., Miravitilles M., Mannino D.M. et al. What is asthma-COPD overlap syndrome? Towards a consensus definition from a round table discussion. Eur. Respir. J. 2016; 48 (3): 664-673. DOI: 10.1183/13993003.00436-2016.Sin D.D., Miravitilles M., Mannino D.M. et al. What is asthma—COPD overlap syndrome? Towards a consensus definition from a round table discussion. Eur. Respir. J. 2016; 48 (3): 664—673. DOI: 10.1183/13993003.00436-2016.Generoso А., Oppenheimer J. Asthma/obstructive pulmonary disease overlap: update on definition, biomarkers, and therapeutics. Curr. Opin. Allergy Clin. Immunol. 2020; 20 (1): 43-47. DOI: 10.1097/ACI.0000000000000596.Generoso А., Oppenheimer J. Asthma/obstructive pulmonary disease overlap: update on definition, biomarkers, and therapeutics. Curr. Opin. Allergy Clin. Immunol. 2020; 20 (1): 43—47. DOI: 10.1097/ACI.0000000000000596.Inoue H., Nagase T., Morita S. et al. Prevalence and characteristics of asthma-COPD overlap syndrome identified by a stepwise approach. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 1803-1810. DOI: 10.2147/COPD.S133859.Inoue H., Nagase T., Morita S. et al. Prevalence and characteristics of asthma—COPD overlap syndrome identified by a stepwise approach. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 1803-1810. DOI: 10.2147/COPD.S133859.Cosio B.G., Soriano J.B., Ldpez-Campos J.L. et al. Defining the asthma-COPD overlap syndrome in a COPD cohort. Chest. 2016; 149 (1): 45-52. DOI: 10.1378/chest.15-1055.Cosio B.G., Soriano J.B., Ldpez-Campos J.L. et al. Defining the asthma-COPD overlap syndrome in a COPD cohort. Chest. 2016; 149 (1): 45-52. DOI: 10.1378/chest.15-1055.Putcha N., Wise R.A. Asthma-chronic obstructive pulmonary disease overlap syndrome: nothing new under the sun. Immunol. Allergy Clin. North. Am. 2016; 36 (3): 515528. DOI: 10.1016/j.iac.2016.03.003.Putcha N., Wise R.A. Asthma-chronic obstructive pulmonary disease overlap syndrome: nothing new under the sun. Immunol. Allergy Clin. North. Am. 2016; 36 (3): 515- 528. DOI: 10.1016/j.iac.2016.03.003.Agusti A., Calverley P.M., Celli B. et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir. Res. 2010; 11 (1): 122. DOI: 10.1186/1465-9921-11-122.Agusti A., Calverley P.M., Celli B. et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir. Res. 2010; 11 (1): 122. DOI: 10.1186/1465-9921-11-122.Benacerraf B. The antigen city of altered autologous proteins a mechanism of autoimmune reactions. Ann. N. J. Acad. Sci. 1965; 124: 126.Benacerraf B. The antigen city of altered autologous proteins a mechanism of autoimmune reactions. Ann. N. J. Acad. Sci. 1965; 124: 126.Федосеев Г.Б., Трофимов В.И., Петрова М.А., ред. Многоликая бронхиальная астма: диагностика, лечение и профилактика. СПб: Нордмед-Издат; 2011.Fedoseev G.B., Trofimov V.I., Petrova M.A., eds. [The many-sided bronchial asthma: diagnosis, treatment and prevention]. St. Petersburg: Nordmed-Izdat; 2011 (in Russian).Mukherjee M., Nair P. Autoimmune responses in severe asthma. Allergy Asthma Immunol. Res. 2018; 10 (5): 428-447. DOI: 10.4168/aair.2018.10.5.428.Mukherjee M., Nair P. Autoimmune responses in severe asthma. Allergy Asthma Immunol. Res. 2018; 10 (5): 428-447. DOI: 10.4168/aair.2018.10.5.428.Nahm D.H., Lee Y.E., Yim E.J. et al. Identification of cytok-eratin 18 as a bronchial epithelial autoantigen associated with nonallergic asthma. Am. J. Respir. Crit. Care Med. 2002; 165 (11): 1536-1539. DOI: 10.1164/rccm.200201-009OC.Nahm D.H., Lee Y.E., Yim E.J. et al. Identification of cytokeratin 18 as a bronchial epithelial autoantigen associated with nonallergic asthma. Am. J. Respir. Crit. Care Med. 2002; 165 (11): 1536-1539. DOI: 10.1164/rccm.200201-009OC.Brandsma C.A., Kerstjens H.A., Geerlings M. et al. The search for autoantibodies against elastin, collagen and decorin in COPD. Eur. Respir. J. 2011; 37 (5): 1289-1292. DOI: 10.1183/09031936.00116710.Brandsma C.A., Kerstjens H.A., Geerlings M. et al. The search for autoantibodies against elastin, collagen and decorin in COPD. Eur. Respir. J. 2011; 37 (5): 1289-1292. DOI: 10.1183/09031936.00116710.Kariyawasam H.H., Semitekolou M., Robinson D.S., Xanthou G. Activin-A: a novel critical regulator of allergic asthma. Clin. Exp. Allergy. 2011; 41 (11): 1505—1514. DOI: 10.1111/j.1365-2222.2011.03784.x.Kariyawasam H.H., Semitekolou M., Robinson D.S., Xanthou G. Activin-A: a novel critical regulator of allergic asthma. Clin. Exp. Allergy. 2011; 41 (11): 1505-1514. DOI: 10.1111/j.1365-2222.2011.03784.x.Гервазиева В.Б., Самойликов П.В., Сверановская В.В. IgE-аутоантитела у больных атопическим дерматитом. Патологическая физиология и экспериементальная терапия. 2009; (1): 19—22.Gervazieva V.B., Samoylikov P.V., Sveranovskaya V.V. [IgE-autoantibodies in patients with atopic dermatitis]. Pato lo -gicheskaya fiziologiya i eksperiemental'naya terapiya. 2009; (1): 19-22 (in Russian).Agusti A., Edwards L.D., Celli B. et al. Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort. Eur. Respir. J. 2013; 42 (3): 636—646. DOI: 10.1183/09031936.00195212.Agusti A., Edwards L.D., Celli B. et al. Characteristics, stability and outcomes of the 2011 GOLD COPD groups in the ECLIPSE cohort. Eur. Respir. J. 2013; 42 (3): 636-646. DOI: 10.1183/09031936.00195212.Ierodiakonou D., Postma D.S., Koppelman G.H. et al. TGF-^1 polymorphisms and asthma severity, airway inflammation, and remodeling. J. Allergy din. Immunol. 2013; 131 (2): 582—585. DOI: 10.1016/j.jaci.2012.08.013.Ierodiakonou D., Postma D.S., Koppelman G.H. et al. TGF-e1 polymorphisms and asthma severity, airway inflammation, and remodeling. J. Allergy Clin. Immunol. 2013; 131 (2): 582-585. DOI: 10.1016/j.jaci.2012.08.013.Karagiannidis C., Akdis M., Holopainen P. et al. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J. Allergy Clin. Immunol. 2004; 114 (6): 1425—1433. DOI: 10.1016/j.jaci.2004.07.014.Karagiannidis C., Akdis M., Holopainen P. et al. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J. Allergy Clin. Immunol. 2004; 114 (6): 1425-1433. DOI: 10.1016/j.jaci.2004.07.014.Packard T.A., Li Q.Z., Cosgrove G.P. et al. COPD is associated with production of autoantibodies to a broad spectrum of self-antigens, correlative with disease phenotype. Immunol. Res. 2013; 55 (1—3): 48—57. DOI: 10.1007/s12026-012-8347-x.Packard T.A., Li Q.Z., Cosgrove G.P. et al. COPD is associated with production of autoantibodies to a broad spectrum of self-antigens, correlative with disease phenotype. Immunol. Res. 2013; 55 (1-3): 48-57. DOI: 10.1007/s12026-012-8347-x.Low Т.В., Greene C.M., O'Neill S.J., McElvanev G.M. Quantification and evaluation of the role of antielastin autoantibodies in the emphysematous lung. Pulm. Med. 2011; 2011: 826160. DOI: 10.1155/2011/826160.Low Т.В., Greene C.M., O'Neill S.J., McElvanev G.M. Quantification and evaluation of the role of antielastin autoantibodies in the emphysematous lung. Pulm. Med. 2011; 2011: 826160. DOI: 10.1155/2011/826160.

The authors declare that there are no conflicts of interest present.