rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.47360/1995-4484-2022-554-559rsp-3222Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHИЛ-31 и ИЛ-33 у больных ревматоидным артритомIL-31 and IL-33 in rheumatoid arthritis patientshttps://orcid.org/0000-0003-2692-399XЛапкинаН. А.LapkinaN. A.

150000,  Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0001-7847-1679БарановА. А.BaranovA. A.

150000,  Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0002-8846-0401АбайтоваН. Е.AbaytovaN. E.

150000,  Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0003-4846-4931ЛевшинН. Ю.LevshinN. Yu.

150000,  Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0002-0444-2346РечкинаО. П.RechkinaO. P.

150000,  Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0002-7979-1313ЛеонтьеваЕ. А.LeontyevaE. A.

150000,  Ярославль, ул. Революционная, 5

150000, Yaroslavl, Revolyutsionnaya str., 5

https://orcid.org/0000-0003-3057-9175АвдееваА. С.AvdeyevaA. S.

115522, Москва, Каширское шоссе, 34а

115522,  Moscow, Kashirskoye Highway, 34A

https://orcid.org/0000-0001-7180-1778АртюховА. С.ArtyukhovA. S.

117997, Москва, ул. Островитянова, 1

117997, Moscow, Ostrovitianova str., 1

https://orcid.org/0000-0002-1598-8360НасоновЕ. Л.NasonovE. L.

115522, Москва, Каширское шоссе, 34а; 119991, Москва, ул. Трубецкая, 8, стр. 2

115522,  Moscow, Kashirskoye Highway, 34A; 119991, Moscow, Trubetskaya str., 8, building 

ФГБОУ ВО «Ярославский государственный медицинский университет» Минздрава РоссииРоссияYaroslavl State Medical UniversityRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian FederationФГАОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияN.I. Pirogov Russian National Research Medical UniversityRussian FederationФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГАОУ ВО «Первый Московский государственный медицинский университет имени И. М. Сеченова» Минздрава России (Сеченовский Университет)РоссияV.A. Nasonova Research Institute of Rheumatology; I.M. Sechenov First Moscow State Medical University of the Ministry of Health Care of Russian Federation (Sechenov University)Russian Federation202211112022605554559Copyright © Лапкина Н.А., Баранов А.А., Абайтова Н.Е., Левшин Н.Ю., Речкина О.П., Леонтьева Е.А., Авдеева А.С., Артюхов А.С., Насонов Е.Л., 20222022Лапкина Н.А., Баранов А.А., Абайтова Н.Е., Левшин Н.Ю., Речкина О.П., Леонтьева Е.А., Авдеева А.С., Артюхов А.С., Насонов Е.Л.Lapkina N.A., Baranov A.A., Abaytova N.E., Levshin N.Y., Rechkina O.P., Leontyeva E.A., Avdeyeva A.S., Artyukhov A.S., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/3222

Цель исследования – изучить клинико-диагностическое значение определения интерлейкина (ИЛ) 31 и ИЛ-33 у больных ревматоидным артритом (РА).

Материал и методы

Материал и методы. Обследовано 154 больных с достоверным диагнозом РА. Сывороточный уровень ИЛ-31 и ИЛ-33 исследовали с помощью мультиплексной технологии хMАР на анализаторе Bio-PlexTM 200 System (BIO-RAD, США). Верхняя граница нормы при исследовании 20 сывороток здоровых доноров составила (M+3σ): для ИЛ-31 – 15,08 пг/мл, для ИЛ-33 – 3,40 пг/мл.

Результаты

Результаты. У больных РА наблюдались более высокие, чем в контрольной группе, уровни (Me (25-й; 75-й перцентили)) ИЛ-31 – 13,75 (5,63; 308,52) и 6,10 (2,87; 8,62) пг/мл (р<0,001) и ИЛ-33 – 18,86 (7,45; 65,95) и 0,52 (0,17; 0,78) пг/мл (р><0,001). Увеличение концентрации ИЛ-33 (более 3,40 пг/мл) отмечено у 87,0% пациентов, ИЛ-31 (более 15,08 пг/мл) – у 48,1% пациентов с РА. У 42,2% (65 из 154) пациентов с РА наблюдалось увеличение концентрации только ИЛ-33, в то время как изолированное увеличение концентрации ИЛ-31 отмечено только у 2 (1,3%) пациентов. Одновременная гиперпродукция ИЛ-33 и ИЛ-31 имела место у 69 (44,9%) пациентов. Выявлена положительная связь показателей клинико-лабораторной активности РА с концентрацией цитокинов: оценка по SDAI (Simplified Disease Activity Index) коррелировала с ИЛ-33 (r=0,36; p><0,05), уровень C-реактивного белка – с ИЛ-31 (r=0,49; p><0,05) и ИЛ-33 (r=0,40; p><0,05). Заключение. Концентрации ИЛ-31, ИЛ-33 повышены у больных РА и коррелируют с показателями воспалительной активности заболевания.>< 0,001) и ИЛ-33 – 18,86 (7,45; 65,95) и 0,52 (0,17; 0,78) пг/мл (р<0,001).

Увеличение концентрации ИЛ-33 (более 3,40 пг/мл) отмечено у 87,0% пациентов, ИЛ-31 (более 15,08 пг/мл) – у 48,1% пациентов с РА. У 42,2% (65 из 154) пациентов с РА наблюдалось увеличение концентрации только ИЛ-33, в то время как изолированное увеличение концентрации ИЛ-31 отмечено только у 2 (1,3%) пациентов. Одновременная гиперпродукция ИЛ-33 и ИЛ-31 имела место у 69 (44,9%) пациентов. Выявлена положительная связь показателей клинико-лабораторной активности РА с концентрацией цитокинов: оценка по SDAI (Simplified Disease Activity Index) коррелировала с ИЛ-33 (r=0,36; p<0,05), уровень C-реактивного белка – с ИЛ-31 (r=0,49; p><0,05) и ИЛ-33 (r=0,40; p><0,05). Заключение. Концентрации ИЛ-31, ИЛ-33 повышены у больных РА и коррелируют с показателями воспалительной активности заболевания.>< 0,05), уровень C-реактивного белка – с ИЛ-31 (r=0,49; p< 0,05) и ИЛ-33 (r=0,40; p< 0,05).

Заключение

Заключение. Концентрации ИЛ-31, ИЛ-33 повышены у больных РА и коррелируют с показателями воспалительной активности заболевания

Objective – to investigate clinical and diagnostic significance of IL-31 and IL-33 determination in patients with rheumatoid arthritis (RA).

Material and methods

Material and methods. 154 patients with a reliable diagnosis of RA were examined. Serum levels of IL-31 and IL-33 were studied using multiplex xMAP technology on Bio-PlexTM 200 System analyzer (BIO-RAD, USA). The upper limit of the norm in the study of 20 healthy donor sera was (M+3σ): IL-31 – 15.08 pg/ml, IL-33 – 3.40 pg/ml.

Results

Results. IL-31 (Me (25th; 75th percentile) – 13.75 (5.63; 308.52) and 6.10 (2.87; 8.62) pg/ml (p<0.001), IL-33 – 18.86 (7.45; 65.95) and 0.52 (0.17; 0.78) pg/ml (p><0.001) levels were observed in RA patients in comparison with the control group. An increase in IL-33 concentration (more than 3.40 pg/ml) was observed in 87.0% of patients, and IL-31 (more than 15.08 pg/ml) in 48.1% of patients with RA. An increase in IL-33 alone was observed in 42.2% (65 of 154 patients) with RA, while an isolated increase in IL-31 concentration was observed in only 2 (1.3%) patients. Simultaneous hyperproduction of IL-33 and IL-31 occurred in 69 (44.9%) patients. We revealed positive correlation of clinical and laboratory parameters of RA with cytokine concentration: SDAI correlated with IL-33 (r=0.36; p><0.05); CRP – with IL-31 (r=0.49; p><0,05) and IL-33 (r=0.40; p><0.05). Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.>< 0.001), IL-33 – 18.86 (7.45; 65.95) and 0.52 (0.17; 0.78) pg/ml (p<0.001) levels were observed in RA patients in comparison with the control group. An increase in IL-33 concentration (more than 3.40 pg/ml) was observed in 87.0% of patients, and IL-31 (more than 15.08 pg/ml) in 48.1% of patients with RA. An increase in IL-33 alone was observed in 42.2% (65 of 154 patients) with RA, while an isolated increase in IL-31 concentration was observed in only 2 (1.3%) patients. Simultaneous hyperproduction of IL-33 and IL-31 occurred in 69 (44.9%) patients. We revealed positive correlation of clinical and laboratory parameters of RA with cytokine concentration: SDAI correlated with IL-33 (r=0.36; p><0.05); CRP – with IL-31 (r=0.49; p><0,05) and IL-33 (r=0.40; p><0.05). Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.>< 0.001) levels were observed in RA patients in comparison with the control group. An increase in IL-33 concentration (more than 3.40 pg/ml) was observed in 87.0% of patients, and IL-31 (more than 15.08 pg/ml) in 48.1% of patients with RA. An increase in IL-33 alone was observed in 42.2% (65 of 154 patients) with RA, while an isolated increase in IL-31 concentration was observed in only 2 (1.3%) patients. Simultaneous hyperproduction of IL-33 and IL-31 occurred in 69 (44.9%) patients. We revealed positive correlation of clinical and laboratory parameters of RA with cytokine concentration: SDAI correlated with IL-33 (r=0.36; p<0.05); CRP – with IL-31 (r=0.49; p><0,05) and IL-33 (r=0.40; p><0.05). Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.>< 0.05); CRP – with IL-31 (r=0.49; p< ,05) and IL-33 (r=0.40; p<0.05)

Conclusion

Conclusion. Concentrations of IL-31 and IL-33 are elevated in RA patients and correlate with the indices of inflammatory activity of the disease.

ревматоидный артритинтерлейкин 31интерлейкин 33мультиплексный анализrheumatoid arthritisinterleukin 31interleukin 33multiplex analysisReferencesSmolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–2038. doi: 10.1016/S0140-6736(16)30173-8Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388(10055):2023–2038. doi: 10.1016/S0140-6736(16)30173-8McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis – Shaping the immunological landscape. Nat Rev Rheumatol. 2016;12(1):63–68. doi: 10.1038/nrrheum.2015.171McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis – Shaping the immunological landscape. Nat Rev Rheumatol. 2016;12(1):63–68. doi: 10.1038/nrrheum.2015.171Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207–214. doi: 10.1097/BOR.0000000000000470Ridgley LA, Anderson AE, Pratt AG. What are the dominant cytokines in early rheumatoid arthritis? Curr Opin Rheumatol. 2018;30(2):207–214. doi: 10.1097/BOR.0000000000000470Alunno A, Carubbi F, Giacomelli R, Gerli R. Cytokines in the pathogenesis of rheumatoid arthritis: New players and therapeutic targets. BMC Rheumatol. 2017;1:3. doi: 10.1186/s41927-017-0001-8Alunno A, Carubbi F, Giacomelli R, Gerli R. Cytokines in the pathogenesis of rheumatoid arthritis: New players and therapeutic targets. BMC Rheumatol. 2017;1:3. doi: 10.1186/s41927-017-0001-8Chen Z, Bozec A, Ramming A, Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2019;15(1):9–17. doi: 10.1038/s41584-Chen Z, Bozec A, Ramming A, Schett G. Anti-inflammatory and immune-regulatory cytokines in rheumatoid arthritis. Nat Rev Rheumatol. 2019;15(1):9–17. doi: 10.1038/s41584-Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: From clinical significance to quantification. Adv Sci (Weinh). 2021;8(15):e2004433. doi: 10.1002/advs.202004433Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: From clinical significance to quantification. Adv Sci (Weinh). 2021;8(15):e2004433. doi: 10.1002/advs.202004433Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23):6008. doi: 10.3390/ijms20236008Kany S, Vollrath JT, Relja B. Cytokines in inflammatory disease. Int J Mol Sci. 2019;20(23):6008. doi: 10.3390/ijms20236008Dong Y, Zhong J, Dong L. IL-33 in rheumatic diseases. Front Med (Lausanne). 2021;8:739489. doi: 10.3389/fmed.2021.739489Dong Y, Zhong J, Dong L. IL-33 in rheumatic diseases. Front Med (Lausanne). 2021;8:739489. doi: 10.3389/fmed.2021.739489Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138(4):984–1010. doi: 10.1016/j.jaci.2016.06.033.Akdis M, Aab A, Altunbulakli C, Azkur K, Costa RA, Crameri R, et al. Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases. J Allergy Clin Immunol. 2016;138(4):984–1010. doi: 10.1016/j.jaci.2016.06.033.Murdaca G, Greco M, Tonacci A, Negrini S, Borro M, Puppo F, et al. IL-33/IL-31 axis in immune-mediated and allergic diseases. Int J Mol Sci. 2019;20(23):5856. doi: 10.3390/ijms20235856Murdaca G, Greco M, Tonacci A, Negrini S, Borro M, Puppo F, et al. IL-33/IL-31 axis in immune-mediated and allergic diseases. Int J Mol Sci. 2019;20(23):5856. doi: 10.3390/ijms20235856Cayrol C. IL-33, an alarmin of the IL-1 family involved in allergic and non allergic inflammation: Focus on the mechanisms of regulation of its activity. Cells. 2021;11(1):107. doi: 10.3390/ cells11010107Cayrol C. IL-33, an alarmin of the IL-1 family involved in allergic and non allergic inflammation: Focus on the mechanisms of regulation of its activity. Cells. 2021;11(1):107. doi: 10.3390/ cells11010107Borgia F, Custurone P, Li Pomi F, Cordiano R, Alessandrello C, Gangemi S. IL-31: State of the art for an inflammation-oriented interleukin. Int J Mol Sci. 2022;23(12):6507. doi: 10.3390/ ijms23126507Borgia F, Custurone P, Li Pomi F, Cordiano R, Alessandrello C, Gangemi S. IL-31: State of the art for an inflammation-oriented interleukin. Int J Mol Sci. 2022;23(12):6507. doi: 10.3390/ ijms23126507Pelaia C, Pelaia G, Longhini F, Crimi C, Calabrese C, Gallelli L, et al. Monoclonal antibodies targeting alarmins: A new perspective for biological therapies of severe asthma. Biomedicines. 2021;9(9):1108. doi: 10.3390/biomedicines9091108Pelaia C, Pelaia G, Longhini F, Crimi C, Calabrese C, Gallelli L, et al. Monoclonal antibodies targeting alarmins: A new perspective for biological therapies of severe asthma. Biomedicines. 2021;9(9):1108. doi: 10.3390/biomedicines9091108Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581. doi: 10.1002/art.27584Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569–2581. doi: 10.1002/art.27584England BR, Tiong BK, Bergman MJ, Curtis JR, Kazi S, Mikuls TR, et al. 2019 update of the American College of Rheumatology recommended rheumatoid arthritis disease activity measures. Arthritis Care Res (Hoboken). 2019;71(12):1540–1555. doi: 10.1002/acr.24042England BR, Tiong BK, Bergman MJ, Curtis JR, Kazi S, Mikuls TR, et al. 2019 update of the American College of Rheumatology recommended rheumatoid arthritis disease activity measures. Arthritis Care Res (Hoboken). 2019;71(12):1540–1555. doi: 10.1002/acr.24042Новиков АА, Александрова ЕН, Герасимов АН, Каратеев ДЕ, Попкова ТВ, Лучихина ЕЛ и др. Применение многопараметрического анализа лабораторных биомаркеров для оценки активности ревматоидного артрита. Научно-практическая ревматология. 2015;53(6):591–595.Novikov AA, Aleksandrova EN, Gerasimov AN, Karateev DE, Popkova TV, Luchikhina EL, et al. Use of multiparameter analysis of laboratory biomarkers to assess rheumatoid arthritis activity. Nauchno-Prakticheskaya Revmatologia = Rheumatology Science and Practice. 2015;53(6):591–595 (In Russ.). doi: 10.14412/1995-4484-2015-591-595Eastman PS, Manning WC, Qureshi F, Haney D, Cavet G, Alexander C, et al. Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal. 2012;70:415–424. doi: 10.1016/j.jpba.2012.06.003Eastman PS, Manning WC, Qureshi F, Haney D, Cavet G, Alexander C, et al. Characterization of a multiplex, 12-biomarker test for rheumatoid arthritis. J Pharm Biomed Anal. 2012;70:415–424. doi: 10.1016/j.jpba.2012.06.003Centola M, Cavet G, Shen Y, Ramanujan S, Knowlton N, Swan KA, et al. Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS One. 2013;8(4):e60635. doi: 10.1371/journal.pone.0060635Centola M, Cavet G, Shen Y, Ramanujan S, Knowlton N, Swan KA, et al. Development of a multi-biomarker disease activity test for rheumatoid arthritis. PLoS One. 2013;8(4):e60635. doi: 10.1371/journal.pone.0060635Laborde CM, Castro-Santos P, Díaz-Peña R. Contribution of multiplex immunoassays to rheumatoid arthritis management: From biomarker discovery to personalized medicine. J Pers Med. 2020;10(4):202. doi: 10.3390/jpm10040202Laborde CM, Castro-Santos P, Díaz-Peña R. Contribution of multiplex immunoassays to rheumatoid arthritis management: From biomarker discovery to personalized medicine. J Pers Med. 2020;10(4):202. doi: 10.3390/jpm10040202Burska A, Boissinot M, Ponchel F. Cytokines as biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014;2014:545493. doi: 10.1155/2014/545493Burska A, Boissinot M, Ponchel F. Cytokines as biomarkers in rheumatoid arthritis. Mediators Inflamm. 2014;2014:545493. doi: 10.1155/2014/545493Palmer G, Talabot-Ayer D, Lamacchia C, Toy D, Seemayer CA, Viatte S, et al. Inhibition of interleukin-33 signaling attenuates the severity of experimental arthritis. Arthritis Rheum. 2009;60(3): 738–749. doi: 10.1002/art.24305Palmer G, Talabot-Ayer D, Lamacchia C, Toy D, Seemayer CA, Viatte S, et al. Inhibition of interleukin-33 signaling attenuates the severity of experimental arthritis. Arthritis Rheum. 2009;60(3): 738–749. doi: 10.1002/art.24305Li Y, Fu Y, Chen H, Liu X, Li M. Blocking interleukin-33 alleviates the joint inflammation and inhibits the development of collagen-induced arthritis in mice. J Immunol Res. 2020;2020:4297354. doi: 10.1155/2020/4297354Li Y, Fu Y, Chen H, Liu X, Li M. Blocking interleukin-33 alleviates the joint inflammation and inhibits the development of collagen-induced arthritis in mice. J Immunol Res. 2020;2020:4297354. doi: 10.1155/2020/4297354Xu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, et al. IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proc Natl Acad Sci U S A. 2008;105(31):10913–10918. doi: 10.1073/ pnas.0801898105Xu D, Jiang HR, Kewin P, Li Y, Mu R, Fraser AR, et al. IL-33 exacerbates antigen-induced arthritis by activating mast cells. Proc Natl Acad Sci U S A. 2008;105(31):10913–10918. doi: 10.1073/ pnas.0801898105Xu D, Jiang HR, Li Y, Pushparaj PN, Kurowska-Stolarska M, Leung BP, et al. IL-33 exacerbates autoantibody-induced arthritis. J Immunol. 2010;184(5):2620–2626. doi: 10.4049/jimmunol.0902685Xu D, Jiang HR, Li Y, Pushparaj PN, Kurowska-Stolarska M, Leung BP, et al. IL-33 exacerbates autoantibody-induced arthritis. J Immunol. 2010;184(5):2620–2626. doi: 10.4049/jimmunol.0902685Kunisch E, Chakilam S, Gandesiri M, Kinne RW. IL-33 regulates TNF-α dependent effects in synovial fibroblasts. Int J Mol Med. 2012;29(4):530–540. doi: 10.3892/ijmm.2012.883Kunisch E, Chakilam S, Gandesiri M, Kinne RW. IL-33 regulates TNF-α dependent effects in synovial fibroblasts. Int J Mol Med. 2012;29(4):530–540. doi: 10.3892/ijmm.2012.883Biton J, Khaleghparast Athari S, Thiolat A, Santinon F, Lemeiter D, Hervé R, et al. In vivo expansion of activated Foxp3+ regulatory T cells and establishment of a type 2 immune response upon IL-33 treatment protect against experimental arthritis. J Immunol. 2016;197(5):1708–1719. doi: 10.4049/jimmunol.1502124Biton J, Khaleghparast Athari S, Thiolat A, Santinon F, Lemeiter D, Hervé R, et al. In vivo expansion of activated Foxp3+ regulatory T cells and establishment of a type 2 immune response upon IL-33 treatment protect against experimental arthritis. J Immunol. 2016;197(5):1708–1719. doi: 10.4049/jimmunol.1502124Rivellese F, Suurmond J, Habets K, Dorjée AL, Ramamoorthi N, Townsend MJ, et al. Ability of interleukin-33- and immune complex-triggered activation of human mast cells to down-regulate monocyte-mediated immune responses. Arthritis Rheumatol. 2015;67(9):2343–2353. doi: 10.1002/art.39192Rivellese F, Suurmond J, Habets K, Dorjée AL, Ramamoorthi N, Townsend MJ, et al. Ability of interleukin-33- and immune complex-triggered activation of human mast cells to down-regulate monocyte-mediated immune responses. Arthritis Rheumatol. 2015;67(9):2343–2353. doi: 10.1002/art.39192Lee EJ, So MW, Hong S, Kim YG, Yoo B, Lee CK. Interleukin-33 acts as a transcriptional repressor and extracellular cytokine in fibroblast-like synoviocytes in patients with rheumatoid arthritis. Cytokine. 2016;77:35–43. doi: 10.1016/j.cyto.2015.10.005Lee EJ, So MW, Hong S, Kim YG, Yoo B, Lee CK. Interleukin-33 acts as a transcriptional repressor and extracellular cytokine in fibroblast-like synoviocytes in patients with rheumatoid arthritis. Cytokine. 2016;77:35–43. doi: 10.1016/j.cyto.2015.10.005Ahmed A, Koma MK. Interleukin-33 triggers B1 cell expansion and its release of monocyte/macrophage chemoattractants and growth factors. Scand J Immunol. 2015;82(2):118–124. doi: 10.1111/sji.12312Ahmed A, Koma MK. Interleukin-33 triggers B1 cell expansion and its release of monocyte/macrophage chemoattractants and growth factors. Scand J Immunol. 2015;82(2):118–124. doi: 10.1111/sji.12312Sattler S, Ling GS, Xu D, Hussaarts L, Romaine A, Zhao H, et al. IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut. J Autoimmun. 2014;50(100):107–122. doi: 10.1016/j.jaut.2014.01.032Sattler S, Ling GS, Xu D, Hussaarts L, Romaine A, Zhao H, et al. IL-10-producing regulatory B cells induced by IL-33 (Breg(IL-33)) effectively attenuate mucosal inflammatory responses in the gut. J Autoimmun. 2014;50(100):107–122. doi: 10.1016/j.jaut.2014.01.032Hong YS, Moon SJ, Joo YB, Jeon CH, Cho ML, Ju JH, et al. Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis. J Korean Med Sci. 2011;26(9):1132–1139. doi: 10.3346/jkms.2011.26.9.1132Hong YS, Moon SJ, Joo YB, Jeon CH, Cho ML, Ju JH, et al. Measurement of interleukin-33 (IL-33) and IL-33 receptors (sST2 and ST2L) in patients with rheumatoid arthritis. J Korean Med Sci. 2011;26(9):1132–1139. doi: 10.3346/jkms.2011.26.9.1132Erfurt S, Hoffmeister M, Oess S, Asmus K, Ritter O, Patschan S, et al. Serum IL-33 as a biomarker in different diseases: Useful parameter or much need for clarification? J Circ Biomark. 2021;10:20–25. doi: 10.33393/jcb.2021.2327Erfurt S, Hoffmeister M, Oess S, Asmus K, Ritter O, Patschan S, et al. Serum IL-33 as a biomarker in different diseases: Useful parameter or much need for clarification? J Circ Biomark. 2021;10:20–25. doi: 10.33393/jcb.2021.2327Mu R, Huang HQ, Li YH, Li C, Ye H, Li ZG. Elevated serum interleukin 33 is associated with autoantibody production in patients with rheumatoid arthritis. J Rheumatol. 2010; 37(10):2006–2013. doi: 10.3899/jrheum.100184Mu R, Huang HQ, Li YH, Li C, Ye H, Li ZG. Elevated serum interleukin 33 is associated with autoantibody production in patients with rheumatoid arthritis. J Rheumatol. 2010; 37(10):2006–2013. doi: 10.3899/jrheum.100184Tang S, Huang H, Hu F, Zhou W, Guo J, Jiang H, et al. Increased IL-33 in synovial fluid and paired serum is associated with disease activity and autoantibodies in rheumatoid arthritis. Clin Dev Immunol. 2013;2013:985301. doi: 10.1155/2013/985301Tang S, Huang H, Hu F, Zhou W, Guo J, Jiang H, et al. Increased IL-33 in synovial fluid and paired serum is associated with disease activity and autoantibodies in rheumatoid arthritis. Clin Dev Immunol. 2013;2013:985301. doi: 10.1155/2013/985301Choi IA, Lee SJ, Park W, Park SH, Shim SC, Baek HJ, et al. Effects of tocilizumab therapy on serum interleukin-33 and interleukin-6 levels in patients with rheumatoid arthritis. Arch Rheumatol. 2018;33(4):389–394. doi: 10.5606/ArchRheumatol.2018.6753Choi IA, Lee SJ, Park W, Park SH, Shim SC, Baek HJ, et al. Effects of tocilizumab therapy on serum interleukin-33 and interleukin-6 levels in patients with rheumatoid arthritis. Arch Rheumatol. 2018;33(4):389–394. doi: 10.5606/ArchRheumatol.2018.6753Xiangyang Z, Lutian Y, Lin Z, Liping X, Hui S, Jing L. Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritis. Cytokine. 2012;58(1):6–9. doi: 10.1016/j.cyto.2011.12.010Xiangyang Z, Lutian Y, Lin Z, Liping X, Hui S, Jing L. Increased levels of interleukin-33 associated with bone erosion and interstitial lung diseases in patients with rheumatoid arthritis. Cytokine. 2012;58(1):6–9. doi: 10.1016/j.cyto.2011.12.010Kageyama Y, Torikai E, Tsujimura K, Kobayashi M. Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: the effect of etanercept on the serum levels of IL-33. Mod Rheumatol. 2012;22(1):89–93. doi: 10.1007/s10165-011-0480-1Kageyama Y, Torikai E, Tsujimura K, Kobayashi M. Involvement of IL-33 in the pathogenesis of rheumatoid arthritis: the effect of etanercept on the serum levels of IL-33. Mod Rheumatol. 2012;22(1):89–93. doi: 10.1007/s10165-011-0480-1Shen J, Shang Q, Wong CK, Li EK, Wang S, Li RJ, et al. IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: A prospective study. Semin Arthritis Rheum. 2015;45(1):18–27. doi: 10.1016/j.semarthrit.2015.02.001Shen J, Shang Q, Wong CK, Li EK, Wang S, Li RJ, et al. IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: A prospective study. Semin Arthritis Rheum. 2015;45(1):18–27. doi: 10.1016/j.semarthrit.2015.02.001Shi LJ, Liu C, Li JH, Zhu XY, Li YN, Li JT. Elevated levels of soluble ST2 were associated with rheumatoid arthritis disease activity and ameliorated inflammation in synovial fibroblasts. Chin Med J (Engl). 2018;131(3):316–322. doi: 10.4103/0366- 6999.223847Shi LJ, Liu C, Li JH, Zhu XY, Li YN, Li JT. Elevated levels of soluble ST2 were associated with rheumatoid arthritis disease activity and ameliorated inflammation in synovial fibroblasts. Chin Med J (Engl). 2018;131(3):316–322. doi: 10.4103/0366- 6999.223847Matsuyama Y, Okazaki H, Hoshino M, Onishi S, Kamata Y, Nagatani K, et al. Sustained elevation of interleukin-33 in sera and synovial fluids from patients with rheumatoid arthritis non-responsive to anti-tumor necrosis factor: Possible association with persistent IL-1β signaling and a poor clinical response. Rheumatol Int. 2012;32(5):1397–1401. doi: 10.1007/s00296-011-1854-6Matsuyama Y, Okazaki H, Hoshino M, Onishi S, Kamata Y, Nagatani K, et al. Sustained elevation of interleukin-33 in sera and synovial fluids from patients with rheumatoid arthritis non-responsive to anti-tumor necrosis factor: Possible association with persistent IL-1β signaling and a poor clinical response. Rheumatol Int. 2012;32(5):1397–1401. doi: 10.1007/s00296-011-1854-6Sellam J, Rivière E, Courties A, Rouzaire PO, Tolusso B, Vital EM, et al. Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis. Arthritis Res Ther. 2016; 18(1):294. doi: 10.1186/s13075-016-1190-zSellam J, Rivière E, Courties A, Rouzaire PO, Tolusso B, Vital EM, et al. Serum IL-33, a new marker predicting response to rituximab in rheumatoid arthritis. Arthritis Res Ther. 2016; 18(1):294. doi: 10.1186/s13075-016-1190-zRivière E, Sellam J, Pascaud J, Ravaud P, Gottenberg JE, Mariette X. Serum IL-33 level is associated with auto-antibodies but not with clinical response to biologic agents in rheumatoid arthritis. Arthritis Res Ther. 2018;20(1):122. doi: 10.1186/s13075-018- 1628-6Rivière E, Sellam J, Pascaud J, Ravaud P, Gottenberg JE, Mariette X. Serum IL-33 level is associated with auto-antibodies but not with clinical response to biologic agents in rheumatoid arthritis. Arthritis Res Ther. 2018;20(1):122. doi: 10.1186/s13075-018- 1628-6

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