References

mrj

Современная ревматология

Modern Rheumatology Journal

1996-70122310-158X

IMA-PRESS, LLC

10.14412/1996-7012-2023-4-103-114

mrj-1454

Research Article

ОБЗОРЫ

REVIEWS

Аутоиммунитет и аутовоспаление - ключ к пониманию патогенеза остеоартрита и разработке новых направлений его профилактики и терапии

Autoimmunity and autoinflammation — the key to understanding the pathogenesis of osteoarthritis and developing new ways for its prevention and therapy

https://orcid.org/0000-0002-5933-5732

Сарвилина

И. В.

Sarvilina

I. V.

Сарвилина Ирина Владиславовна.

344002, Ростов-на-Дону, ул. Социалистическая, 74

Irina V. Sarvilina.

74, Socialisticheskaya Street, Rostov-on-Don 344002

isarvilina@mail.ru

https://orcid.org/0000-0002-6068-3080

Лила

А. М.

Lila

A. M.

Кафедра ревматологии ФГБОУ ДПО «РМАНПО» Минздрава России.

115522, Москва, Каширское шоссе, 34А; 125993, Москва, ул. Баррикадная, 2/1, стр. 1

Department of Rheumatology, Russian Medical Academy of Continuing Professional Education.

34A, Kashirskoe Shosse, Moscow 115522; 2/1, Barrikadnaya Street, Build. 1, Moscow 125993

https://orcid.org/0000-0001-7017-0898

Алексеева

Л. И.

Alekseeva

L. I.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

https://orcid.org/0000-0002-7663-710X

Громова

О. A.

Gromova

O. A.

119333, Москва, ул. Вавилова, 44

44, Vavilov Street, Moscow 119333

https://orcid.org/0000-0001-8218-3223

Таскина

Е. А.

Taskina

E. A.

115522, Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

ООО «Медицинский центр «Новомедицина»РоссияLLC "Medical Center" Novomeditsina"Russian Federation

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»; ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияV.A. Nasonova Research Institute of Rheumatology; Russian Medical Academy of Continuing Professional EducationRussian Federation

ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»РоссияV.A. Nasonova Research Institute of RheumatologyRussian Federation

Федеральный исследовательский центр «Информатика и управление» Российской академии наукРоссияFederal Research Center "Informatics and Management"Russian Federation

2023

20082023

174103114

2023

Сарвилина И.В., Лила А.М., Алексеева Л.И., Громова О.A., Таскина Е.А.

Sarvilina I.V., Lila A.M., Alekseeva L.I., Gromova O.A., Taskina E.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://mrj.ima-press.net/mrj/article/view/1454

В обзоре рассматривается весь спектр известных на сегодня аутоантигенов при остеоартрите (ОА) и обсуждается их роль в возникновении и/или сохранении синовита и запуске последующего разрушения суставного хряща с развитием аутоиммунной реакции и аутовоспаления. Большой интерес представляют методы лекарственной профилактики ОА, учитывающие реакции аутоиммунитета и связанного с ним аутовоспаления, в том числе с применением фармаконутрицевтиков.

Представлены доклинические и клинические исследования безопасности и эффективности фармаконутрицевтиков, содержащих нативный коллаген II типа. Обсуждается четкая связь состава/химической структуры компонентов коллагена с его механизмом действия и эффективностью.

Новые комбинированные фармаконутрицевтики разрабатываются с учетом аутоиммунного патогенеза ОА и направлены на уменьшение проявлений аутовоспаления (хондроитина сульфат, глюкозамина сульфат). Они имеют оптимальное соотношение активных компонентов с достаточным уровнем доказательности, что позволяет получить потенцирование их положительных фармакологических эффектов.

The review considers the full spectrum of currently known autoantigens in osteoarthritis (OA) and discusses their role in the development and/or persistence of synovitis and the initiation of subsequent destruction of articular cartilage with the development of an autoimmune response and auto-inflammation. Of great interest are methods of drug prevention of OA considering autoimmunity responses and associated auto-inflammation, including the use of pharmaconutraceuticals.

Preclinical and clinical studies of the safety and efficacy of pharmaconutraceuticals containing native type II collagen are presented. A clear relationship between the composition/chemical structure of the collagen components and its mechanism of action and efficacy is discussed. Taking into account the autoimmune pathogenesis of OA, new combined pharmaconutraceuticals aimed at reducing the manifestations of autoinflammation (chondroitin sulfate, glucosamine sulfate) are developed. They have an optimal ratio of active ingredients with a sufficient level of evidence, which allows enhancing their beneficial pharmacological effects.

остеоартритаутоиммунитетаутовоспалениехондроитина сульфатглюкозамина сульфатнативный колллаген II типафармаконутрицевтикантиген-специфическая иммунотерапия

osteoarthritisautoimmunityautoinflammationchondroitin sulfateglucosamine sulfatenative type II collagenpharmaconutraceuticalantigen-specific immunotherapy

Статья опубликована при поддержке компании ЗАО «ФармФирма «Сотекс».

Publication of this article has been supported by Sotex PharmFirma.

References1

Felson D, Lawrence R, Dieppe P, Hirsch R. Osteoarthritis: new insights. Part 1: the disease and its risk factors. Ann Intern Med. 2000 Oct 17;133(8):635-46. doi: 10.7326/0003-4819-133-8-200010170-00016.

Hunter D, March L, Chew M. Osteoarthritis in 2020 and Beyond: A Lancet Commission. Lancet. 2020 Nov 28;396(10264):1711-1712. doi: 10.1016/S0140-6736(20)32230-3. Epub 2020 Nov 4.

Hunter D, Bierma-Zeinstra S. Osteoarthritis. Lancet. 2019 Apr 27;393(10182):1745-1759. doi: 10.1016/S0140-6736(19)30417-9.

Murray C, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859): 2197-223. doi: 10.1016/S0140-6736(12)61689-4.

Murray C, Vos T, Lozano R, et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990—2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859): 2197-223. doi: 10.1016/S0140-6736(12)61689-4.

Cross M, Smith E, Hoy D, et al. The global burden of hip and knee osteoarthritis: estimates from the Global Burden of Disease 2010 study. Ann Rheum Dis. 2014 Jul;73(7):1323-30. doi: 10.1136/annrheumdis-2013-204763. Epub 2014 Feb 19.

Насонов ЕЛ, редактор. Российские кли-нические рекомендации. Ревматология. Москва: ГЭОТАР-Медиа; 2017.

Nasonov EL, editor. Rossiiskie klinicheskie rekomendatsii. Revmatologiya [Russian clinical guidelines. Rheumatology]. Moscow: GEOTAR-Media; 2017.

Loeser R, Goldring S, Scanzello C, Goldring M. Osteoarthritis: A Disease of the Joint as An Organ. Arthritis Rheum. 2012 Jun; 64(6):1697-707. doi: 10.1002/art.34453. Epub 2012 Mar 5.

Tomohiro K, Yang Х, Hiroshi N, Kusuki N. Neoantigens in osteoarthritic cartilage. Curr Opin Rheumatol. 2004 Sep;16(5):604-8. doi: 10.1097/01.bor.0000133661.52599.bf.

Banerjee S, Poole A. Immunity to cartilage proteoglycans. J Rheumatol Suppl. 1992 Apr; 33:36-9.

Choi E, Gatenby P, McGill N, et al. Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, autoimmune connective tissue diseases, and chronic inflammatory syndromes. Ann Rheum Dis. 1988 Apr;47(4):313-22. doi: 10.1136/ard.47.4.313.

Bruyere O, Honvo G, Veronese N, et al. An updated algorithm recommendation for the management of knee osteoarthritis from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO). Semin Arthritis Rheum. 2019 Dec;49(3):337-350. doi: 10.1016/j.semarthrit.2019.04.008. Epub 2019 Apr 30.

Kolasinski S, Neogi T, Hochberg M, et al. 2019 American College of Rheumatology / Arthritis Foundation Guideline for the Mana-gement of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020 Feb;72(2):149-162. doi: 10.1002/acr.24131. Epub 2020 Jan 6.

Kolasinski S, Neogi T, Hochberg M, et al. 2019 American College of Rheumatology / Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee. Arthritis Care Res (Hoboken). 2020 Feb;72(2):149-162. doi: 10.1002/acr.24131. Epub 2020 Jan 6.

Сарвилина ИВ, Лила АМ, Громова ОА. Новая фармаконутрицевтическая композиция для антиген-специфической профилактики и вспомогательной терапии костно-мышечных заболеваний. Русский медицинский журнал. 2023;(2):44-50.

Sarvilina IV, Lila AM, Gromova OA. A new pharmaconutraceutical composition for anti-gen-specific prevention and adjunctive therapy of musculoskeletal diseases. Russkii meditsinskii zhurnal. 2023;(2):44-50. (In Russ.).

Mobasheri A, Bay-Jensen A, van Spil W, et al. Osteoarthritis Year in Review 2016: biomarkers (biochemical markers). Osteoarthritis Cartilage. 2017 Feb;25(2):199-208. doi: 10.1016/j.joca.2016.12.016. Epub 2017 Jan 16.

Blanco F. Osteoarthritis year in review 2014: we need more biochemical biomarkers in qualification phase. Osteoarthritis Cartilage. 2014 Dec;22(12):2025-32. doi: 10.1016/j.joca.2014.09.009. Epub 2014 Nov 22.

Camacho-Encina M, Balboa-Barreiro V, Rego-Perez I, et al. Discovery of an autoanti-body signature for the early diagnosis of knee osteoarthritis: data from the Osteoarthritis Initiative. Ann Rheum Dis. 2019 Dec;78(12): 1699-1705. doi: 10.1136/annrheumdis-2019-215325. Epub 2019 Aug 30.

Honsawek S, Tanavalee A, Sakdinakiattikoon M, et al. Correlation of plasma and synovial fluid osteopontin with disease severity in knee osteoarthritis. Clin Biochem. 2009 Jun;42(9):808-12. doi: 10.1016/j.clinbiochem.2009.02.002. Epub 2009 Feb 13.

Naito K, Takahashi M, Kushida K, et al. Measurement of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in patients with knee osteoarthritis: comparison with generalized osteoarthritis. Rheumatology. 1999;38(6):510-5.

Tomer Y, Shoenfeld Y. Ageing and autoantibodies. Autoimmunity. 1988;1(2):141-9. doi: 10.3109/08916938809001927.

Yang M, Doyle H, Clarke S, et al. Oxidative modifications in tissue pathology and autoimmune disease. Antioxid Redox Signal. 2018 Nov 10;29(14):1415-1431. doi: 10.1089/ars.2017.7382. Epub 2017 Dec 11.

Ahmed U, Anwar A, Savage R, et al. Biomarkers of early stage osteoarthritis, rheumatoid arthritis and musculoskeletal health. Sci Rep.2015 Mar 19;5:9259. doi: 10.1038/srep09259.

Nguyen H, James E. Immune recognition of citrullinated epitopes. Immunology. 2016 Oct;149(2):131-8. doi: 10.1111/imm.12640. Epub 2016 Aug 17.

Santos A, Lindner A. Protein posttranslational modifications: roles in aging and age-related disease. Oxid Med Cell Longev. 2017; 2017:5716409. doi: 10.1155/2017/5716409. Epub 2017 Aug 15.

Van Delft MAM, van Beest S, Kloppenburg M, et al. Presence of autoantibodies in erosive hand osteoarthritis and association with clinical presentation. J Rheumatol. 2019 Jan;46(1):101-105. doi: 10.3899/jrheum.180256. Epub 2018 Sep 15.

Strollo R, Ponchel F, Malmstrom V, et al. Autoantibodies to posttranslationally modified type II collagen as potential biomarkers for rheumatoid arthritis. Arthritis Rheum. 2013 Jul;65(7):1702-12. doi: 10.1002/art.37964.

Xie X, van Delft MAM, Shuweihdi F, et al. Auto-antibodies to post-translationally modified proteins in osteoarthritis. Osteoarthritis Cartilage. 2021 Jun;29(6):924-933. doi: 10.1016/j.joca.2021.03.008. Epub 2021 Mar 20.

Brown L, Berse B, van de Water L. Ex-pression and distribution of osteopontin in human tissues: widespread association with luminal epithelial surfaces. Mol Biol Cell. 1992 Oct;3(10):1169-80. doi: 10.1091/mbc.3.10.1169.

Dodds R, Connor J, James I, et al. Human osteoclasts, not osteoblasts, deposit osteopontin onto resorption surfaces: an in vitro and ex vivo study of remodeling bone. J Bone Miner Res. 1995 Nov;10(11):1666-80. doi: 10.1002/jbmr.5650101109.

Naot D, Sionov R, Ish-Shalom D. CD44: structure, function, and association with the malignant process [review]. Adv Cancer Res. 1997;71:241-319. doi: 10.1016/s0065-230x(08)60101-3.

Sakata M, Tsuruha JI, Masuko-Hongo K, et al. Autoantibodies to Osteopontin in Patients with Osteoarthritis and Rheumatoid Arthritis. J Rheumatol. 2001 Jul;28(7):1492-5.

Leroux JY, Guerassimov A, Cartman A, et al. Poole Immunity to the G1 Globular Do-main of the Cartilage Proteoglycan Aggrecan Can Induce Inflammatory Erosive Polyarthritis and Spondylitis in BALB/c Mice but Immunity to G1 Is Inhibited by Covalently Bound Keratan Sulfate In Vitro and In Vivo. J Clin Invest. 1996 Feb 1;97(3):621-32. doi: 10.1172/JCI118458.

Mikecz K, Glant T, Poole A. Immunity to cartilage proteoglycans in BALB/c mice with progressive polyarthritis and ankylosing spondylitis induced by injection of human cartilage proteoglycan. Arthritis Rheum. 1987 Mar; 30(3):306-18. doi: 10.1002/art.1780300310.

Glant T, Mikecz K, Roughley P, et al. Age-related changes in protein-related epitopes of human articular cartilage proteoglycans. Biochem J. 1986 May 15;236(1):71-5. doi: 10.1042/bj2360071.

Glant T, Mikecz K, Roughley P, et al. Age-related changes in protein-related epito-pes of human articular cartilage proteoglycans. Biochem J. 1986 May 15;236(1):71-5. doi: 10.1042/bj2360071.

Nishioka K. Autoimmune response in cartilage-delivered peptides in a patient with osteoarthritis. Arthritis Res Ther. 2004;6(1):6-7. doi: 10.1186/ar1025. Epub 2003 Dec 5.

Sandy J. Contentious Issue Finds Some Clarity: On the Independent and Complementary Roles of Aggrecanase Activity and MMP Activity in Human Joint Aggrecanolysis. Osteoarthritis Cartilage. 2006 Feb;14(2): 95-100. doi: 10.1016/j.joca.2005.09.004. Epub 2005 Oct 27.

Fan Z, Bau B, Yang H, et al. Freshly Isolated Osteoarthritic Chondrocytes are Catabolically More Active Than Normal Chondrocytes, But Less Responsive to Catabolic Stimulation With Interleukin-1? Arthritis Rheum. 2005 Jan;52(1):136-43. doi: 10.1002/art.20725.

Van der Kraan P. Differential Role of Transforming Growth Factor-Beta in an Osteoarthritic or a Healthy Joint. J Bone Metab. 2018 May;25(2):65-72. doi: 10.11005/jbm.2018.25.2.65. Epub 2018 May 31.

Brubaker S, Bonham K, Zanoni I, Kagan J. Innate immune pattern recognition: a cell biological perspective. Annu Rev Immunol. 2015;33:257-90. doi: 10.1146/annurev-immunol-032414-112240. Epub 2015 Jan 2.

Janeway C, Travers P, Walport M, Shlomchik M. The Immune System in Health and Disease. New York: Garland Science; 2001.

Taylor A, Verhagen J, Blaser K, et al. Mechanisms of immune suppression by interleukin-10 and transforming growth factor-beta: the role of T regulatory cells. Immunology. 2006 Apr;117(4):433-42. doi: 10.1111/j.1365-2567.2006.02321.x.

Lee K, Stott R, Zhao G, et al. TGF-beta-producing regulatory B cells induce regulatory T cells and promote transplantation tolerance. Eur J Immunol. 2014 Jun;44(6):1728-36. doi: 10.1002/eji.201344062. Epub 2014 May 3.

Rojko J, Evans M, Price S, et al. Formation, clearance, deposition, pathogenicity, and identification of biopharmaceutical-related immune complexes: review and case studies. Toxicol Pathol. 2014 Jun;42(4):725-64. doi: 10.1177/0192623314526475. Epub 2014 Apr 3.

Takeda K, Akira S. Toll-like receptors in innate immunity. Int Immunol. 2005 Jan;17(1): 1-14. doi: 10.1093/intimm/dxh186.

Radstake T, Roelofs M, Jenniskens Y, et al. Expression of toll-like receptors 2 and 4 in rheumatoid synovial tissue and regulation by proinflammatory cytokines interleukin-12 and interleukin-18 via interferon-gamma. Arthritis Rheum. 2004 Dec;50(12):3856-65. doi: 10.1002/art.20678.

Van Lent P, Blom A, Grevers L, et al. Toll-like receptor 4 induced FcgammaR expression potentiates early onset of joint inflammation and cartilage destruction during immune complex arthritis: Toll-like receptor 4 largely regulates FcgammaR expression by interleukin 10. Ann Rheum Dis. 2007 Mar;66(3): 334-40. doi: 10.1136/ard.2006.057471. Epub 2006 Oct 26.

Yuan GH, Masuko-Hongo K, Kato T, Nishioka K. Immunologic intervention in the pathogenesis of osteoarthritis. Arthritis Rheum. 2003 Mar;48(3):602-11. doi: 10.1002/art.10768.

Deligne C, Casulli S, Pigenet A, et al. Differential Expression of Interleukin-17 and Interleukin-22 in Inflamed and Non-Inflamed Synovium From Osteoarthritis Patients. Osteoarthritis Cartilage. 2015 Nov;23(11): 1843-52. doi: 10.1016/j.joca.2014.12.007.

Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of colla-gen-induced arthritis in IL-17-deficient mice. J Immunol. 2003 Dec 1;171(11):6173-7. doi: 10.4049/jimmunol.171.11.6173.

Nakae S, Nambu A, Sudo K, Iwakura Y. Suppression of immune induction of collagen-induced arthritis in IL-17-deficient mice. J Immunol. 2003 Dec 1;171(11):6173-7. doi: 10.4049/jimmunol.171.11.6173.

Sato K, Suematsu A, Okamoto K, et al. Th17 function as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006 Nov 27; 203(12):2673-82. doi: 10.1084/jem.20061775. Epub 2006 Nov 6.

Kraus V, McDaniel G, Huebner J, et al. Direct In Vivo Evidence of Activated Macrophages in Human Osteoarthritis. Osteoarthritis Cartilage. 2016 Sep;24(9):1613-21. doi: 10.1016/j.joca.2016.04.010. Epub 2016 Apr 12.

Thomson A, Hilkens CMU. Synovial Macrophages in Osteoarthritis: The Key to Understanding Pathogenesis? Front Immunol. 2021 Jun 15;12:678757. doi: 10.3389/fimmu.2021.678757. eCollection 2021.

Kaplan M, Radic M. Neutrophil extracellular traps: double-edged swords of innate immunity. J Immunol. 2012 Sep 15;189(6):2689-95. doi: 10.4049/jimmunol.1201719.

Devaney J, Greene C, Taggart C, et al. Neutrophil elastase up-regulates interleukin-8 via toll-like receptor 4. FEBS Lett. 2003 Jun 5; 544(1-3):129-32. doi: 10.1016/s0014-5793 (03)00482-4.

Devaney J, Greene C, Taggart C, et al. Neutrophil elastase upregulates interleukin-8 via toll-like receptor 4. FEBS Lett. 2003 Jun 5; 544(1-3):129-32. doi: 10.1016/s0014-5793 (03)00482-4.

Khandpur R, Carmona-Rivera C, Vivekanandan-Giri A, et al. NETs are a source of citrullinated autoantigens and stimulate inflammatory responses in rheumatoid arthritis. Sci Transl Med. 2013 Mar 27;5(178):178ra40. doi: 10.1126/scitranslmed.3005580.

Hultqvist M, Olofsson P, Holmberg J, et al. Enhanced autoimmunity, arthritis, and encephalomyelitis in mice with a reduced oxidative burst due to a mutation in the Ncf1 gene. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34): 12646-51. doi: 10.1073/pnas.0403831101. Epub 2004 Aug 13.

Kadler K, Baldock C, Bella J, Boot-Handford R. Collagens at a glance. J Cell Sci. 2007 Jun 15;120(Pt 12):1955-8. doi: 10.1242/jcs.03453.

Kim W, Yoo W, Park W, et al. IgG antibodies to type II collagen reflect inflammatory activity in patients with rheumatoid arthritis. J Rheumatol. 2000 Mar;27(3):575-81.

Galber R, Fonseca J, Fujimura P, et al. Anti-type II collagen antibodies detection and avidity in patients with oligoarticular and polyarticular forms of juvenile idiopathic arthritis. Immunol Lett. 2015 May;165(1):20-5. doi: 10.1016/j.imlet.2015.03.006. Epub 2015 Mar 20.

Williams R. Collagen-induced arthritis as a model for rheumatoid arthritis. Methods Mol Med. 2004;98:207-16. doi: 10.1385/1-59259-771-8:207.

Stuart J, Townes A, Kang A. Nature and specificity of the immune response to collagen in type II collalgen-induced arthritis in mice. J Clin Invest. 1982 Mar;69(3):673-83. doi: 10.1172/jci110495.

Stuart J, Townes A, Kang A. Collagen autoimnune airthritis. Annu Rev Immunol. 1984;2:199-218. doi: 10.1146/annurev.iy.02.040184.001215.

Gilliam B, Chauhan A, Moore T. Evaluation of anti-citrullinated type II collagen and anti-citrullinated vimentin antibodies in patients with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 2013 Aug 29;11(1):31. doi: 10.1186/1546-0096-11-31.

Suwannalai P, van de Stadt L, Radner H, et al. Avidity maturation of anti-citrullinated protein antibodies in rheumatoid arthritis. Arthritis Rheum. 2012 May;64(5):1323-8. doi: 10.1002/art.33489.

Yoshida M, Tsuji M, Kurosaka D, et al. Autoimmunity to citrullinated type II collagen in rheumatoid arthritis. Mod Rheumatol. 2006; 16(5):276-81. doi: 10.1007/s10165-006-0498-y.

Terato K, Shimozuru Y, Katayama K, et al. Specificity of antibodies to type II collagen in rheumatoid arthritis. Arthritis Rheum. 1990 Oct; 33(10):1493-500. doi: 10.1002/art.1780331006.

Cook A, Rowley M, Stockman A, et al. Specificity of antibodies to type II collagen in early rheumatoid arthritis. J Rheumatol. 1994 Jul;21(7):1186-91.

Tarkowski A, Holmdahl R, Rubin K, et al. Patterns of autoreactivity to collagen type II in autoimmune MRL/l mice. Clin Exp Immunol. 1986 Feb;63(2):441-9.

Mullazehi M, Mathsson L, Lampa J, Ronnelid J. High anti-collagen type-II anti-body levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset. Ann Rheum Dis. 2007 Apr; 66(4):537-41. doi: 10.1136/ard.2006.064782. Epub 2006 Oct 13.

Mullazehi M, Mathsson L, Lampa J, Ronnelid J. High anti-collagen type-II antibody levels and induction of proinflammatory cytokines by anti-collagen antibody-containing immune complexes in vitro characterise a distinct rheumatoid arthritis phenotype associated with acute inflammation at the time of disease onset. Ann Rheum Dis. 2007 Apr; 66(4):537-41. doi: 10.1136/ard.2006.064782. Epub 2006 Oct 13.

Mathsson L, Tejde A, Carlson K, et al. Cryoglobulin-induced cytokine production via Fcgamma RIIa: inverse effects of complement blockade on the production of TNF-alpha and IL-10. Implications for the growth of malignant B-cell clones. Br J Haematol. 2005 Jun;129(6):830-8. doi: 10.1111/j.1365-2141.2005.05538.x.

Miller E. The structure of fibril-forming collagens. Biology, chemistry and pathology of collagen. Ann N Y Acad Sci. 1985;460:1-13. doi: 10.1111/j.1749-6632.1985.tb51152.x.

Nandakumar K, Holmdahl R. Efficient promotion of collagen antibody induced arthritis (CAIA) using four monoclonal antibodies specific for the major epitopes recognized in both collagen induced arthritis and rheumatoid arthritis. J Immunol Methods. 2005 Sep;304(1-2):126-36. doi: 10.1016/j.jim.2005.06.017.

Using a cocktail of anti-collagen type II antibodies induces a synchronized model of arthritis in just a few days. BioTechniques. 2010;48:237. doi 10.2144/000113384.

Min D, Cho M, Lee S, et al. Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts. Arthritis Rheum. 2004 Apr;50(4):1146-55. doi: 10.1002/art.20133.

Franitza S, Hershkoviz R, Kam N, et al. TNF-alpha associated with extracellular matrix fibronectin provides a stop signal for chemotactically migrating T cells. J Immunol. 2000 Sep 1;165(5):2738-47. doi: 10.4049/jimmunol.165.5.2738.

Kim M, Day C, Morrison N. MCP-1 is induced by receptor activator of nuclear factor-{kappa}B ligand, promotes human osteo-clast fusion, and rescues granulocyte macrophage colony-stimulating factor suppression of osteoclast formation. J Biol Chem. 2005 Apr 22;280(16):16163-9. doi: 10.1074/jbc.M412713200. Epub 2005 Feb 17.

Strid J, Tan L, Strobel S, et al. Epicutaneous Immunization with Type II Collagen Inhibits both Onset and Progression of Chronic Collagen-Induced Arthritis. PLoS One. 2007 Apr 18;2(4):e387. doi: 10.1371/journal.pone.0000387.

Szabo S, Kim S, Costa G, et al. A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell. 2000 Mar 17;100(6):655-69. doi: 10.1016/s0092-8674(00)80702-3.

Zheng W, Flavell R. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997 May 16;89(4):587-96. doi: 10.1016/s0092-8674(00)80240-8.

Yates A, Callard R, Stark J. Combining cytokine signalling with T-bet and GATA-3 regulation in Th1 and Th2 differentiation: a model for cellular decision-making. J Theor Biol. 2004 Nov 21;231(2):181-96. doi: 10.1016/j.jtbi.2004.06.013.

Zhao X, Long J, Liang F, et al. Different protective efficacies of a novel antigen-specific DNA vaccine encoding chicken type II collagen via intramuscular, subcutaneous, and intravenous vaccination against experimental rheumatoid arthritis. Biomed Pharmacother. 2021 Dec;144:112294. doi: 10.1016/j.biopha.2021.112294. Epub 2021 Oct 12.

Wei W, Zhang L, Xu J, et al. A multicenter, double-blind, randomized, controlled phase III clinical trial of chicken type II collagen in rheumatoid arthritis. Arthritis Res Ther. 2009; 11(6):R180. doi: 10.1186/ar2870. Epub 2009 Dec 1.

Batsalova T, Dzhambazov B. Significance of Type II Collagen Posttranslational Modifications: From Autoantigenesis to Improved Diagnosis and Treatment of Rheumatoid Arthritis. Int J Mol Sci. 2023 Jun 8;24(12): 9884. doi: 10.3390/ijms24129884.

Tordesillas L, Berin M. Mechanisms of Oral Tolerance. Clin Rev Allergy Immunol. 2018 Oct;55(2):107-117. doi: 10.1007/s12016-018-8680-5.

Faria A, Weiner H. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases. Clin Dev Immunol. 2006 Jun-Dec;13(2-4):143-57. doi: 10.1080/17402520600876804.

Weiner H. Oral tolerance: immune mechanisms and treatment of autoimmune diseases. Immunol Today. 1997 Jul;18(7):335-43. doi: 10.1016/s0167-5699(97)01053-0.

Coombes J, Powrie F. Dendritic Cells in Intestinal Immune Regulation. Nat Rev Immunol. 2008 Jun;8(6):435-46. doi: 10.1038/nri2335.

Asnagli H, Martire D, Belmonte N, et al. Type 1 Regulatory T Cells Specific for Collagen Type II as an Efficient Cell-Based Therapy in Arthritis. Arthritis Res Ther. 2014 May 22;16(3):R115. doi: 10.1186/ar4567.

Pabst O, Mowat A. Oral tolerance to food protein. Mucosal Immunol. 2012 May;5(3): 232-9. doi: 10.1038/mi.2012.4. Epub 2012 Feb 8.

Nagler-Anderson C, Bober L, Robinson M, et al. Suppression of Type II Collagen-Induced Arthritis by Intragastric Administration of Soluble Type II Collagen. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7443-6. doi: 10.1073/pnas.83.19.7443.

Thompson H, Harper N, Bevan D, Staines N. Suppression of Collagen Induced Arthritis by Oral Administration of Type II Collagen: Changes in Immune and Arthritic Responses Mediated by Active Peripheral Suppression. Autoimmunity. 1993;16(3):189-99. doi: 10.3109/08916939308993327.

Trollmo C, Sollerman C, Carlsten H, et al. The gut as an inductive site for synovial and extra-articular immune responses in rheumatoid arthritis. Ann Rheum Dis. 1994 Jun;53(6): 377-82. doi: 10.1136/ard.53.6.377.

Bakilan F, Armagan O, Ozgen M, et al. Effects of Native Type II Collagen Treatment on Knee Osteoarthritis: A Randomized Controlled Trial. Eurasian J Med. 2016 Jun;48(2): 95-101. doi: 10.5152/eurasianjmed.2015.15030.

Lugo J, Saiyed Z, Lane N. Efficacy and Tolerability of an Undenatured Type II Collagen Supplement in Modulating Knee Osteoarthritis Symptoms: A Multicenter Randomized, Double-Blind, Placebo-Controlled Study. Nutr J. 2016 Jan 29;15:14. doi: 10.1186/s12937-016-0130-8.

Mehra A, Anand P, Borate M, et al. A Non-Interventional, Prospective, Multicentric Real Life Indian Study to Assess Safety and Effectiveness of Un-Denatured Type 2 Collagen in Management of Osteoarthritis. Int J Res Orthop. 2019;5:315-320.

Costa A, Cunha Teixeira V, Pereira M, et al. Associated Strengthening Exercises to Undenatured Oral Type II Collagen (UC-II). A Randomized Study in Patients Affected by Knee Osteoarthritis. Muscles Ligaments Ten-dons J. 2020;10:481-492.

Sadigursky D, Magnavita V, Sa C, et al. Undenatured Collagen Type II for the Treatment of Osteoarthritis of the Knee. Acta Ortop Bras. 2022 Apr 15;30(2):e240572. doi: 10.1590/1413-785220223002240572. eCollection 2022.

Jain A, Jain K, Vijayaraghavan N. AflaB2® and Osteoarthritis: A Multicentric, Observational, Post-Marketing Surveillance Study in Indian Patients Suffering from Knee Osteoarthritis. Int J Res Orthop. 2020;7:110.

McAlindon T, Nuite M, Krishnan N, et al. Change in Knee Osteoarthritis Cartilage Detected by Delayed Gadolinium Enhanced Magnetic Resonance Imaging Following Treatment with Collagen Hydrolysate: A Pilot Randomized Controlled Trial. Osteoarthritis Cartilage. 2011 Apr;19(4):399-405. doi: 10.1016/j.joca.2011.01.001. Epub 2011 Jan 18.

Kumar S, Sugihara F, Suzuki K, et al. A Double-Blind, Placebo-Controlled, Ran-domised, Clinical Study on the Effectiveness of Collagen Peptide on Osteoarthritis: Effect of Collagen Peptide on Arthritis. J Sci Food Agric. 2015 Mar 15;95(4):702-7. doi: 10.1002/jsfa.6752. Epub 2014 Jun 24.

Kumar S, Sugihara F, Suzuki K, et al. A Double-Blind, Placebo-Controlled, Randomised, Clinical Study on the Effectiveness of Collagen Peptide on Osteoarthritis: Effect of Collagen Peptide on Arthritis. J Sci Food Agric. 2015 Mar 15;95(4):702-7. doi: 10.1002/jsfa.6752. Epub 2014 Jun 24.

100

Kilinc B, Oc Y, Alibakan G, et al. An Observational 1-Month Trial on the Efficacy and Safety of Promerim for Improving Knee Joint. Clin Med Insights Arthritis Musculoskelet Disord. 2018 Feb 11;11:1179544118757496. doi: 10.1177/1179544118757496. eCollection 2018.

101

Puigdellivol J, Comellas Berenger C, Perez Fernandez M, et al. Effectiveness of a Dietary Supplement Containing Hydrolyzed Collagen, Chondroitin Sulfate, and Glucosamine in Pain Reduction and Functional Capacity in Osteoarthritis Patients. J Diet Suppl. 2019;16(4): 379-389. doi: 10.1080/19390211.2018.1461726. Epub 2018 Apr 27.

102

Schon C, Knaub K, Alt W, et al. UC-II Undenatured Type II Collagen for Knee Joint Flexibility: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study. J Integr Complement Med. 2022 Jun; 28(6):540-548. doi: 10.1089/jicm.2021.0365. Epub 2022 Apr 4.

103

Knaub K, Schon C, Alt W, et al. UC-II® Undenatured Type II Collagen Reduces Knee Joint Discomfort and Improves Mobility in Healthy Subjects: A Randomized, Double-Blind, Placebo-Controlled Clinical Study. J Clin Trials. 2022;12:1-8.

104

Bongers CCWG, Ten Haaf DSM, Catoire M, et al. Effectiveness of Collagen Supple-mentation on Pain Scores in Healthy Indivi-duals with Self-Reported Knee Pain: A Randomized Controlled Trial. Appl Physiol Nutr Metab. 2020 Jul;45(7):793-800. doi: 10.1139/apnm-2019-0654. Epub 2020 Jan 28.

Bongers CCWG, Ten Haaf DSM, Catoire M, et al. Effectiveness of Collagen Supple-mentation on Pain Scores in Healthy Individuals with Self-Reported Knee Pain: A Randomized Controlled Trial. Appl Physiol Nutr Metab. 2020 Jul;45(7):793-800. doi: 10.1139/apnm-2019-0654. Epub 2020 Jan 28.

105

Martel-Pelletier J, Kwan Tat S, Pelletier J. Effects of chondroitin sulfate in the pathophysiology of the osteoarthritic joint: a narrative review. Osteoarthritis Cartilage. 2010 Jun;18 Suppl 1:S7-11. doi: 10.1016/j.joca.2010.01.015. Epub 2010 Apr 27.

106

Аннефельд М. Новые данные о глюкозамине сульфате. Научно-практическая ревматология. 2005;(4):76-80.

Annefeld M. New data about glucosamin sulphate. Nauchno-prakticheskaya revmatologiya. 2005;43(4):76-80. (In Russ.).

107

Chan P, Caron J, Orth M. Effect of glucosamine and chondroitin sulfate on regulation of gene expression of proteolytic enzymes and their inhibitors in interleukin-1-challenged bovine articular cartilage explants. Am J Vet Res. 2005 Nov;66(11):1870-6. doi: 10.2460/ajvr.2005.66.1870.

108

Honvo G, Bruyere O, Geerinck A, et al. Efficacy of chondroitin sulfate in patients with knee osteoarthritis: a comprehensive meta-analysis exploring inconsistencies in randomized, placebo-controlled trials. Adv Ther. 2019 May;36(5):1085-1099. doi: 10.1007/s12325-019-00921-w. Epub 2019 Mar 16.

109

Pelletier J, Raynauld J, Beaulieu A, et al. Chondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multi-centre exploratory study. Arthritis Res Ther. 2016 Nov 3;18(1):256. doi: 10.1186/s13075-016-1149-0.

110

Сарвилина ИВ, Минасов ТБ, Лила АМ и др. Об эффективности парентеральной формы высокоочищенного хондроитина сульфата в режиме периоперационной подготовки к эндопротезированию коленных суставов. Русский медицинский журнал. 2022;(7):7-16.

Sarvilina IV, Minasov TB, Lila AM, et al. On the efficacy of the parenteral form of highly purified chondroitin sulfate in the mode of perioperative preparation for total knee arthroplasty. Russkii meditsinskii zhurnal. 2022;(7): 7-16. (In Russ.).

111

Gregori D, Giacovelli G, Minto C, et al. Association of pharmacological treatments with long-term pain control in patients with knee osteoarthritis: a systematic review and meta-analysis. JAMA. 2018 Dec 25;320(24): 2564-2579. doi: 10.1001/jama.2018.19319.

112

Торшин ИЮ, Лила АМ, Наумов АВ и др. Метаанализ клинических исследований эффективности лечения остеоартита препаратом Хондрогард. Фармакоэкономика. Современная фармакоэкономика и фар-макоэпидемиология. 2020;13(4):388-399.

Torshin IYu, Lila AM, Naumov AV, et al. Meta-analysis of clinical trials of osteoarthritis treatment effectiveness with Chondroguard. Farmakoekonomika. Sovremennaya farmakoekonomika i farmakoepidemiologiya. 2020;13(4): 388-399. (In Russ.).

113

Лила АМ, Ткачева ОН, Наумов АВ и др. Место и роль парентеральной формы хондроитина сульфата в терапии остеоартрита: мультидисциплинарный консенсус. Русский медицинский журнал. 2021; (6):68-74.

Lila AM, Tkacheva ON, Naumov AV, et al. Place and role of the parenteral form of chondroitin sulfate in the treatment of osteoarthritis: multidisciplinary consensus. Russkii meditsinskii zhurnal. 2021;(6):68-74. (In Russ.).

114

Алексеева ЛИ, Аникин СГ, Зайцева ЕМ и др. Исследование эффективности, переносимости и безопасности препарата Хондрогард у пациентов с остеоартрозом. Русский медицинский журнал. 2013;32:1624.

Alekseeva LI, Anikin SG, Zaitseva EM, et al. Efficacy, tolerability and safety study of Chondrogard in patients with osteoarthritis. Russkii meditsinskii zhurnal. 2013;32:1624. (In Russ.).

115

Bruyere O, Burlet N, Delmas P, et al. Evaluation of Symptomatic Slow-Acting Drugs in Osteoarthritis Using the GRADE System. BMC Musculoskelet Disord. 2008 Dec 16;9:165. doi: 10.1186/1471-2474-9-165.

116

Towbeed T, Maxwell L, Anastassiades T, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev. 2005 Apr 18;2005(2):CD002946. doi: 10.1002/14651858.CD002946.pub2.

117

Herrero-Beaumont G, Ivorra J, Del Carmen Irabado M, et al. Glucosamine sulfate in the treatment of knee osteoarthritis symptoms: a randomized, double-blind, placebo-controlled study using acetaminophen as side comparator. Arthritis Rheum. 2007 Feb;56(2):555-67. doi: 10.1002/art.22371.

118

Pawelka K, Gatterova J, Olejarova M, et al. Glucosamine sulfate use and delay of progression of knee osteoarthritis: a 3 year, randomized, placebo-controlled, doubleblind study. Arch Intern Med. 2002 Oct 14; 162(18):2113-23. doi: 10.1001/archinte.162.18.2113.

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