Preview

Научно-практическая ревматология

Расширенный поиск

Новые возможности фармакотерапии иммуновоспалительных ревматических заболеваний: фокус на ингибиторы интерлейкина 17

https://doi.org/10.14412/1995-4484-2017-68-86

Полный текст:

Аннотация

В последние годы большое внимание привлечено к Th17-клеткам, синтезирующим интерлейкин 17 (ИЛ17), в отличие от Th1- и Th2-клеток, «маркерными» цитокинами которых являются соответственно интерферон γ (ИФНγ) и ИЛ4. Полагают, что именно патологическая активация и экспансия Th17-клеток играют ведущую роль в развитии широкого спектра иммуновоспалительных заболеваний (ИВЗ) человека, включая ревматоидный артрит (РА), псориаз, анкилозирующий спондилит (АС), псориатический артрит (ПсА), воспалительные заболевания кишечника, системную красную волчанку, которые ранее рассматривались как Th1-зависимые заболевания, связанные в первую очередь с гиперпродукцией ИЛ2 и ИФНγ. Это послужило мощным стимулом для разработки новых генно-инженерных биологических препаратов, механизм действия которых основан на блокировании патологических эффектов ИЛ17, других связанных с активацией Th17-клеток цитокинов, или «малых молекул», интерферирующих с факторами транскрипции, регулирующими синтез этих цитокинов. В обзоре обсуждаются современные исследования, касающиеся механизмов регуляции образования и функциональной активности цитокинов семейства ИЛ17, и доказательства значения этих цитокинов в патогенезе ИВЗ. Особое внимание уделяется клинической эффективности и безопасности моноклональных антител к ИЛ17А – препарату секукинумаб – при псориазе, ПсА, АС и РА.

Об авторе

Е. Л. Насонов
ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой» ФГБОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России
Россия

научный руководитель ФГБНУ НИИР им. В.А. Насоновой, заведующий кафедрой ревматологии ИПО ГБОУ ВПО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, академик РАН, профессор, докт. мед. наук

115522 Москва, Каширское шоссе, 34А

119991 Москва, ул. Трубецкая, 8, стр. 2



Список литературы

1. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Ann Rev Immunol. 1989;7:145-73. doi: 10.1146/annurev.iy.07.040189.001045

2. Miossec P, Korn T, Kuchroo VK. Interleukin-17 and type 17 helper T cells. N Engl J Med. 2009;361:888-98. doi: 10.1056/NEJMra0707449

3. Miossec P, Kolls JK. Targeting IL-17 and Th17 cells in chronic inflammation. Nat Rev Drug Discov. 2012;11:763-76. doi: 10.1038/nrd3794

4. Rouvier E, Luciani MF, Mattei MG, et al. CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene. J Immunol. 1993;150:5445-56.

5. Painter YZ, Fanslow SL, Ulrich WC, et al. Human IL-17: a novel cytokine derived from T cells. J. Immunol. 1995;155:5483-6.

6. Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology. 2010;129:311-21. doi: 10.1111/j.1365-2567.2009.03240

7. Gaffen SL. Recent advances in the IL-17 cytokine family. Curr Opin Immunol. 2011;23:613-9. doi: 10.1016/j.coi.2011.07.006

8. Kleinschek MA, Owyang AM, Joyce-Shaikh B, et al. IL-25 regulates Th17 function in autoimmune inflammation. J Exp Med. 2007;204:161-70. doi: 10.1084/jem.20061738

9. Aarvak T, Chabaud M, Miossec P, Natvig JB. IL-17 is produced by some proinflammatory Th1/Th0 cells but not by Th2 cells. J Immunol. 1999;162:1246-51.

10. Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature. 2003;421:744-8. doi: 10.1038/nature01355

11. Teng MW, Bowman EP, McElwee JJ, et al. IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases. Nat Med. 2015;2:719-29. doi: 10.1038/nm.3895

12. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Ann Rev Immunol. 2009;27:485-517. doi: 10.1146/annurev.immunol.021908.132710

13. Noack M, Miossec P. Th17 and regulatory T cell balance in autoimmune and inflammatory diseases. Autoimmun Rev. 2014;13:668-77. doi: 10.1016/j.autrev.2013.12.004

14. Sabat R, Ouyang W, Wolk K. Therapeutic opportunities of the IL-22-IL-22R1 system. Nat Rev Drug Discov. 2014;13:21-38. doi: 10.1038/nrd4176

15. Cua DJ, Tato CM. Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol. 2010;10:479-89. doi: 10.1038/nri2800

16. Isalovic N, Daigo K, Mantovani A, Selmi C. Interleukin-17 and innate immunity in infections and chronic inflammation. J Autoimmun. 2015;60:1-11. doi: 10.1016/j.jaut.2015.04.006

17. Beringer A, Noack M, Miossec P. IL-17 in chronic inflammation: from discovery to targeting. Trends Molec Med. 2016;22:230-41. doi: 10.1016/j.molmed.2016.01.001

18. Benedetti G, Miossec P. Interleukin 17 contributes to the chronicity of inflammatory diseases such as rheumatoid arthritis. Eur J Immunol. 2014;44:339-47. doi: 10.1002/eji.201344184

19. Fragoulis GE, Siebert S, McInnes IB. Therapeutic targeting of IL-17 and IL-23 cytokines in immune-mediated disease. Ann Rev Med. 2016:67:337-53. doi: 10.1146/annurev-med- 051914-0219444

20. Boehncke W-H, Schon MP. Psoriasis. Lancet. 2015;386:983-94. doi: 10.1016/S0140-6736(14)61909-7

21. Sakkas LI, Bogdanos DP. Are psoriasis and psoriatic arthritis the same disease? The IL- 23/IL-17 axis data. Autoimmun Rev. 2017 Jan;16(1):10-15. doi: 10.1016/j.autrev.2016.09.015

22. Zaba LC, Fuentes-Duculan J, Eungdamrong NJ, et al. Psoriasis is characterized by accumulation of immunostimulatory and Th1/Th17 cell-polarizing myeloid dendritic cells. J Invest Dermatol. 2009;129:79-88. doi: 10.1038/jid.2008.194

23. Lowes MA, Suarez-Farinas M, Krueger JG. Immunology of psoriasis. Ann Rev Immunol. 2014;32:227-55. doi: 10.1146/annurevimmunol-032713-120225

24. Marinoni B, Celebelli A, Massarotti MS, Selmi C. The Th17 axis in psoriatic disease: pathogenesis and therapeutic implications. Autoimmun Highlights. 2014;5:9-19. doi: 10.1007/s13317-013-0057-4

25. Arakawa A, Siewert K, Stohr J, et al. Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med. 2015;212:2203-12. doi: 10.1084/jem.20151093

26. Lande R, Botti E, Jandus C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621. doi: 10.1038/ncomms6621

27. Di Cesare A, Di Meglio P, Nestle FO. The IL-23/Th17 axis in the immunopathogenesis of psoriasis. J Invest Dermatol. 2009;129:1339-50. doi: 10.1038/jid.2009.59

28. Taurog JD, Chhabra A, Colbert RA. Ankylosing spondylitis and axial spondyloarthritis. New Engl J Med. 2016;374:2563-74. doi: 10.1056/NEJMral406182

29. Smith JA, Colbert RA. Review: The interleukin-23/interleukin-17 axis in spondyloarthritis pathogenesis: Th17 and beyond. Arthritis Rheum. 2014;66:231-41. doi: 10.1002/art.38291

30. Hreggvidsdottir HS, Noordenbos T, Baeten DL. Inflammatory pathways in spondyloarthritis. Mol Immunol. 2014;57:28-37. doi: 10.1016/j.molimm.2013.07.016

31. Suzuki E, Mellins ED, Gershwin ME, et al. The IL-23/IL-17 axis in psoriatic arthritis. Autoimmun Rev. 2014;13:496-502. doi: 10.1016/j.autrev.2014.01.050

32. Галушко ЕА, Гордеев АВ. Современный взгляд на патогенез спондилоартритов – молекулярные механизмы. Научно-практическая ревматология. 2015;53(3):299-307 [Galushko EA, Gordeev AV. Modern idea on the pathogenesis of spondyloarthritis: molecular mechanisms. Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(3):299-307 (In Russ.)]. doi: 10.14412/1995- 4484-2015-299-307

33. Lories RJ, Baeten DL. Differences in pathophysiology between rheumatoid arthritis and ankylosing spondylitis. Clin Exp Rheumatol. 2009;27:S10-4.

34. Reveille JD, Sims AM, Danoy P, et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat Genet. 2010;42:123-7. doi: 10.1038/ng.513

35. Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis-insights into pathogenesis. Nat Rev Rheumatol. 2016;12:81-91. doi: 10.1038/nrrheum.2015.133

36. Farh KK, Marson A, Zhu J, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015; 518:337-43. doi: 10.1038/nature13835

37. Glatigny S, Fert I, Blaton MA, et al. Proinflammatory Th17 cells are expanded and induced by dendritic cells in spondylarthritisprone HLA-B27-transgenic rats. Arthritis Rheum. 2012;64:110-20. doi: 10.1002/art.33321

38. Abe Y, Ohtsuji M, Ohtsuji N, et al. Ankylosing enthesitis associated with up-regulated IFN-gamma and IL-17 production in (BXSB x NZB) F(1) male mice: a new mouse model. Mod Rheumatol. 2009;19:316-22.

39. Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4- CD8- entheseal resident T cells. Nat Med. 2012;18:1069- 76. doi: 10.1038/nm.2817

40. Zhang L, Li YG, Li YH, et al. Increased frequencies of Th22 cells as well as Th17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PloS One. 2012;7:e31000. doi: 10.1371/journal.pone.0031000

41. Wendling D, Cedoz JP, Racadot E, Dumoulin G. Serum IL-17, BMP-7, and bone turnover markers in patients with ankylosing spondylitis. Joint Bone Spine. 2007;74:304-5. doi: 10.1016/j.jbspin.2006.11.005

42. Mei Y, Pan F, Gao J, et al. Increased serum IL-17 and IL-23 in the patient with ankylosing spondylitis. Clin Rheumatol. 2011;30:269-73. doi: 10.1007/s10067-010-1647-4

43. Liu W, Wu YH, Zhang L, et al. Elevated serum levels of IL-6 and IL-17 may associate with the development of ankylosing spondylitis. Int J Clin Exp Med. 2015;8:17362-76.

44. Wang X, Lin Z, Wei Q, et al. Expression of IL-23 and IL-17 and effect of IL-23 on IL-17 production in ankylosing spondylitis. Rheumatol Int. 2009;29:1343-7. doi: 10.1007/s00296-009-0883-x

45. Coffre M, Roumier M, Rybczynska M, et al. Combinatorial control of TH17 and TH1 cell function by genetic variation at genes associated with the IL-23 signaling pathway in spondyloarthritis. Arthritis Rheum. 2013;65:1510-21. doi: 10.1002/art.37936

46. Singh R, Aggarwal A, Misra R. TH1/TH17 cytokine profiles in patients with reactive arthritis/undifferentiated spondyloarthropathy. J Rheumatol. 2007;34:2285-90.

47. Jandus C, Bioley G, Rivals JP, et al. Increased numbers of circulating polyfunctional TH17 memory cells in patients with seronegative spondylarthritides. Arthritis Rheum. 2008;58:2307-17. doi: 10.1002/art.23655

48. Shen H, Goodall JC, Hill Gaston JS. Frequency and phenotype of peripheral blood TH17 cells in ankylosing spondylitis and rheumatoid arthritis. Arthritis Rheum. 2009;60:1647-56. doi: 10.1002/art.24568

49. Shao LL, Zhang L, Hou Y, et al. Increased frequencies of TH22 cells as well as TH17 cells in the peripheral blood of patients with ankylosing spondylitis and rheumatoid arthritis. PLoS ONE. 2012;7:e31000. doi: 10.1371/journal.pone.0051339

50. Bowness P, Ridley A, Shaw J, et al. Th17 cells expressing KIR3DL2+ and responsive to HLA-B27 homodimers are increased in ankylosing spondylitis. J Immunol. 2011;186:2672- 80. doi: 10.4049/jimmunol.1002653

51. Jansen DT, Hameetman M, van Bergen J, et al. IL-17-producing CD4+ T cells are increased in early, active axial spondyloarthritis including patients without imaging abnormalities. Rheumatology (Oxford). 2015;54:728-35. doi: 10.1093/rheumatology/keu382

52. Gracey E, Yao Y, Green B, et al. Sexual dimorphism in the Th17 signature of ankylosing spondylitis. Arthritis Rheum. 2016;68:679-89. doi: 10.1002/art.39464

53. Van der Horst-Bruinsma IE, Zack DJ, Szumski A, Koenig AS. Female patients with ankylosing spondylitis: analysis of the impact of gender across treatment studies. Ann Rheum Dis. 2013;72:1221-4. doi: 10.1136/annrheumdis-2012-202431

54. Appel H, Maier R, Wu P, et al. Analysis of IL-17(+) cells in facet joints of patients with spondyloarthritis suggests that the innate immune pathway might be of greater relevance than the Th17- mediated adaptive immune response. Arthritis Res Ther. 2011;13:R95. doi: 10.1186/ar3370

55. Noordenbos T, Yeremenko N, Gofita I, et al. Interleukin-17-positive mast cells contribute to synovial inflammation in spondylarthritis. Arthritis Rheum. 2012;64:99-109. doi: 10.1002/art.33396

56. Leijten EF, van Kempen TS, Boes M, et al. Brief report: enrichment of activated group 3 innate lymphoid cells in psoriatic arthritis synovial fluid. Arthritis Rheum. 2015;67:2673-8. doi: 10.1002/art.39261

57. Ciccia F, Guggino G, Rizzo A, et al. Type 3 innate lymphoid cells producing IL-17 and IL-22 are expanded in the gut, in the peripheral blood, synovial fluid and bone marrow of patients with ankylosing spondylitis. Ann Rheum Dis. 2015;74:1739-47. doi: 10.1136/annrheumdis-2014-206323

58. Stoll ML. Gut microbes, immunity, and spondyloarthritis. Clin Immunol. 2015;159:134-42. doi: 10.1016/j.clim.2015.05.001

59. Costello ME, Elewaut D, Kenna TJ, Brown MA. Microbes, the gut and ankylosing spondylitis. Arthritis Res Ther. 2013;15:214. doi: 10.1186/ar4228

60. Галушко ЕА, Гордеев АВ. Концепция «болезни барьерного органа» в патогенезе спондилоартритов. Научно-практическая ревматология. 2016;54(2):199-205 [Galushko EA, Gordeev AV. The concept of barrier organ disease in the pathogenesis of spondyloarthritis. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2016;54(2):199-205 (In Russ.)]. doi: 10.14412/1995-4484-2016-199-205

61. DeLay ML, Turner MJ, Klenk EI, et al. HLA-B27 misfolding and the unfolded protein response augment interleukin-23 production and are associated with Th17 activation in transgenic rats. Arthritis Rheum. 2009;60:2633-43. doi: 10.1002/art.24763

62. Lin P, Bach M, Asquith M, et al. HLA-B27 and human beta2-microglobulin affect the gut microbiota of transgenic rats. PloS One. 2014;9:e105684. doi: 10.1371/journal.pone.0105684

63. Ivanov II, Atarashi K, Manel N, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139:485- 98. doi: 10.1016/j.cell.2009.09.033

64. Yang Y, Torchinsky MB, Gobert M, et al. Focused specificity of intestinal TH17 cells towards commensal bacterial antigens. Nature. 2014;510:152-6. doi: 10.1038/nature13279

65. Zielinski CE, Mele F, Aschenbrenner D, et al. Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta. Nature. 2012;484:514-8. doi: 10.1038/nature10957

66. Ciccia F, Bombardieri M, Principato A, et al. Overexpression of interleukin-23, but not interleukin-17, as an immunologic signature of subclinical intestinal inflammation in ankylosing spondylitis. Arthritis Rheum. 2009;60:955-65. doi: 10.1002/art.24389

67. Wright PB, McEntegart A, McCarey D, et al. Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation. Rheumatology (Oxford). 2016;55:120- 32. doi: 10.1093/rheumatology/kev245

68. Takahashi N, Vanlaere I, de Rycke R, et al. IL-17 produced by Paneth cells drives TNF- induced shock. J Exp Med. 2008;205:1755-61. doi: 10.1084/jem.20080588

69. Sherlock JP, Buckley CD, Cua DJ. The critical role of interleukin-23 in spondyloarthropathy. Mol Immunol. 2014;57:38-43. doi: 10.1016/j.molimm.2013.06.010

70. Kehl AS, Corr M, Weisman MH. Review: Enthesitis: New insights into pathogenesis, diagnostic modalities, and treatment. Arthritis Rheum. 2016;68:312-22. doi: 10.1002/art.39458

71. Lubberts E. The IL-23-IL-17 axis in inflammatory arthritis. Nat Rev Rheumatol. 2015;11:415-29. doi: 10.1038/nrrheum.2015.53

72. Насонов ЕЛ, Денисов ЛН, Станислав МЛ. Интерлейкин 17 –новая мишень для антицитокиновой терапии иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2013;51(5):545-52 [Nasonov EL, Denisov LN, Stanislav ML. Interleukin-17 is a new target for anti-cytokine therapy of immune inflammatory rheumatic diseases. Nauchno-Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(5):545-52 (In Russ.)]. doi: 10.14412/1995-4484-2013-1547

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

74. Bush K, Farmer K, Walker J, Kirkham B. Reduction of joint inflammation and bone erosion in rat adjuvant arthritis by treatment with interleukin-17 receptor IgG1 Fc fusion protein. Arthritis Rheum. 2002;46:802-5. doi: 10.1002/art.10173

75. Chao C, Chen S, Adamopoulos I, et al. Anti-IL-17A therapy protects against bone erosion in experimental models of rheumatoid arthritis. Autoimmunity. 2011;44:243-52. doi: 10.3109/08916934.2010.517815

76. Koenders M, Lubberts E, Oppers-Walgreen B, et al. Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1. Am J Pathol. 2005;167:141-9. doi: 10.1016/S0002- 9440(10)62961-6

77. Ishiguro A, Akiyama T, Adachi H, et al. Therapeutic potential of anti-interleukin-17A aptamer: suppression of interleukin- 17A signaling and attenuation of autoimmunity in two mouse models. Arthritis Rheum. 2011;63:455-66. doi: 10.1002/art.30108

78. Metawi S, Abbas D, Kamal M, Ibrahim M. Serum and synovial fluid levels of interleukin-17 in correlation with disease activity in patients with RA. Clin Rheumatol. 2011;30:1201-7. doi: 10.1007/s10067-011-1737-y

79. Moran E, Mullan R, McCormick J, et al. Human rheumatoid arthritis tissue production of IL-17A drives matrix and cartilage degradation: synergy with tumour necrosis factor-α, Oncostatin M and response to biological therapies. Arthritis Res Ther. 2009;11:R113. doi: 10.1186/ar2772

80. Suurmond J, Dorjee A, Boon M, et al. Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibody-positive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther. 2011;13:R150. doi: 10.1186/ar3466

81. Ziolkowska M, Koc A, Luszczykiewicz G, et al. High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporine A-sensitive mechanism. J Immunol. 2000;164:2832-8. doi: 10.4049/jimmunol.164.5.2832

82. Raza K, Falciani F, Curnow SJ, et al. Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin. Arthritis Res Ther. 2005;7:R784-95. doi: 10.1186/ar1733

83. Kokkonen H, Sö derströ m I, Rocklö v J, et al. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010;62:383-91. doi: 10.1002/art.27186

84. Kochi Y, Okada Y, Suzuki A, et al. A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. Nat Genetics. 2010;42:515-9. doi: 10.1038/ng.583

85. Annunziato F, Santarlasci V, Maggi L, et al. Reasons for rarity of Th17 cells in inflammatory sites of human disorders. Semin Immunol. 2013;25:299-304. doi: 10.1016/j.smim.2013.10.011

86. Kotake S, Nanke Y, Yago T, et al. Elevated ratio of Th17 cellderived Th1 cells (CD161(+)Th1 Cells) to CD161(+)Th17 cells in peripheral blood of early-onset rheumatoid arthritis patients. Biomed Res Int. 2016;2016:4186027. doi: 10.1155/2016/4186027

87. Насонов ЕЛ. Метотрексат при ревматоидном артрите – 2015: новые факты и идеи. Научно-практическая ревматология. 2015;53:421-33 [Nasonov EL. Methotrexate in rheumatoid arthritis – 2015: New facts and ideas. Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2015;53(4):421-33 (In Russ.)]. doi: 10.14412/1995- 4484-2015-421-433

88. Chen D, Chen Y, Chen H, et al. Increasing levels of circulating Th17 cells and interleukin- 17 in rheumatoid arthritis patients with an inadequate response to anti-TNF-α therapy. Arthritis Res Ther. 2012;13:R126. doi: 10.1186/ar3431

89. Alzabin S, Abraham S, Taher T, et al. Incomplete responses of inflammatory arthritis to TNFα blockade is associated with the Th17 pathway. Ann Rheum Dis. 2012;71:1741-8. doi: 10.1136/annrheumdis-2011-201024

90. Ambarus C, Yeremenko N, Tak PP, Baeten D. Pathogenesis of spondyloarthritis: autoimmune or autoinflammatory? Curr Opin Rheumatol. 2012;24:351-8. doi: 10.1097/BOR.0b013e3283534df4

91. Belasco J, Louie JS, Gulati N, et al. Comparative genomic profiling of synovium versus skin lesions in psoriatic arthritis. Arthritis Rheum. 2015;67:934-44. doi: 10.1002/art.38995

92. Van Baarsen LG, Lebre MC, van der Coelen D, et al. Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy. Arthritis Res Ther. 2014 Aug 22;16:426. doi: 10.1186/s13075-014-0426-z

93. Mendes D, Correia M, Barbedo M, et al. Behcet’s disease –a contemporary review. J Autoimmun. 2009;32:178-88. doi: 10.1016/j.jaut.2009.02.011

94. Hamzaoui K, Bouali E, Ghorbel I, et al. Expression of Th-17 and RORγt mRNA in Behcet’s Disease. Med Sci Monit. 2011;17:227-34. doi: 10.12659/MSM.881720

95. Takeuchi M, Usui Y, Okunuki Y, et al. Immune responses to interphotoreceptor retinoid- binding protein and S-antigen in Behcet’s patients with uveitis. Invest Ophthalmol Vis Sci. 2010;51:3067-75. doi: 10.1167/iovs.09-4313

96. Chi W, Zhu X, Yang P, et al. Upregulated IL-23 and IL-17 in Behcet patients with active uveitis. Invest Ophthalmol Vis Sci. 2008;49:3058-64. doi: 10.1167/iovs.07-1390

97. Mizuki N, Meguro A, Ota M, et al. Genome-wide association studies identify IL23R- IL12RB2 and IL10 as Behcet’s disease susceptibility loci. Nat Genet. 2010;42:703-6. doi: 10.1038/ng.624

98. Remmers EF, Cosan F, Kirino Y, et al. Genome-wide association study identifies variants in the MHC class I, IL10, and IL23RIL12RB2 regions associated with Behcet’s disease. Nat Genet. 2010;42:698-702. doi: 10.1038/ng.625

99. Rahman A, Isenberg DA. Systemic lupus erythematosus. N Engl J Med. 2008;358:929-39. doi: 10.1056/NEJMra071297

100. Kyttaris VC, Zhang Z, Kuchroo VK, et al. Cutting edge: IL-23 receptor deficiency prevents the development of lupus nephritis in C57BL/6-lpr/lpr mice. J Immunol. 2010;184:4605-9. doi: 10.4049/jimmunol.0903595

101. Pisitkun P, Ha H-L, Wang H, et al. Interleukin-17 cytokines are critical in development of fatal lupus glomerulonephritis. Immunity. 2012;37:1104-15. doi: 10.1016/j.immuni.2012.08.014

102. Amarilyo G, Lourenco EV, Fu-Dong Shi, La Cava A. IL-17 promotes murine lupus. J Immunol. 2014;193:540-3. doi: 10.4049/jimmunol.1400931

103. Wong CK, Lit LC, Tam LC, et al. Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th-17-mediated inflammation in autoimminity. Clin Immunol. 2008;127:385-93. doi: 10.1016/j.clim.2008.01.019

104. Chen XQ, Yu YC, Deng HH, et al. Plasma IL-17A is increased in new-onset SLE patients and associated with disease activity. J Clin Immunol. 2010;30:221-5. doi: 10.1007/s10875-009-9365-x

105. Vincent FB, Northcott M, Hoi A, et al. Clinical associations of serum interleukin-17 in systemic lupus erythematosus. Arthritis Res Ther. 2013;15:R97. doi: 10.1186/ar4277

106. Zhao XF, Pan HF, Yuan H, et al. Increased serum interleukin 17 in patients with systemic lupus erythematosus. Mol Biol Rep. 2010;37:81-5. doi: 10.1007/s11033-009-9533-3

107. Chen DY, Chen YM, Wen MC, et al. The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis. Lupus. 2012;21:1385-96. doi: 10.1177/0961203312457718

108. Crispin JC, Oukka M, Bayliss G, et al. Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys. J Immunol. 2008;15:181:8761-6 doi: 10.4049/jimmunol.181.12.8761

109. Yang J, Chu Y, Yang X, et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum. 2009;60:1472-83. doi: 10.1002/art.24499

110. Wang Y, Ito S, Chino Y, et al. Laser microdissection-based analysis of cytokine balance in the kidneys of patients with lupus nephritis. Clin Exp Immunol. 2010;159:1-10. doi: 10.1111/j.1365-2249.2009.04031.x

111. Du J, Li Z, Shi J, Bi L. Associations between serum interleukin-23 levels and clinical characteristics in patients with systemic lupus erythematosus. J Int Med Res. 2014;42:1123- 30. doi: 10.1177/0300060513509130

112. Rana A, Minz RW, Aggarwal R, et al. Gene expression of cytokines (TNF-α, IFN-γ), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus. Lupus. 2012;21:1105- 12. doi: 10.1177/0961203312451200

113. Smith S, Gabhann JN, Higgs R, et al. Enhanced interferon regulatory factor 3 binding to the interleukin-23p19 promoter correlates with enhanced interleukin-23 expression in systemic lupus erythematosus. Arthritis Rheum. 2012;64:1601-9. doi: 10.1002/art.33494

114. Puwipirom H, Hirankarn N, Sodsai P, et al. Increased interleukin-23 receptor(+) T cells in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12:R215. doi: 10.1186/ar3194

115. Mok MY, Wu HJ, Lo Y, Lau CS. The relation of interleukin 17 (IL-17) and IL-23 to Th1/Th2 cytokines and disease activity in systemic lupus erythematosus. J Rheumatol 2010;37:2046- 52. doi: 10.3899/jrheum.100293

116. Yang X-Y, Wang H-Y, Zhao X-Y, et al. Th22, but not Th17 might be a good index to predict the tissue involvement of systemic lupus erythematosus. J Clin Immunol. 2013;33:767-74. doi: 10.1007/s10875-013-9878-1

117. Brito-Zeron P, Ramos-Casals M. Advances in the understanding and treatment of systemic complications in Sjö gren’s syndrome. Curr Opin Rheumatol. 2015;26:520-7. doi: 10.1097/BOR.0000000000000096

118. Nguyen CG, Yin H, Lee BH, et al. Pathogenic effect of interleukin-17A in induction of Sjö gren’s syndrome-like disease using adenovirus-mediated gene transfer. Arthritis Res Ther. 2010;12, no. 6, article R220. doi: 10.1186/ar3207

119. Lin X, Rui K, Deng J, et al. Th17 cells play a critical role in the development of experimental Sjö gren’s syndrome. Ann Rheum Dis. 2015;74:1302-10. doi: 10.1136/annrheumdis-2013-204584

120. Nguyen CQ, Hu MH, Li Y, et al. Salivary gland tissue expression of interleukin-23 and interleukin-17 in Sjö gren’s syndrome: findings in humans and mice. Arthritis Rheum. 2008;58:734-43.doi: 10.1002/art.23214

121. Fei Y, Zhang W, Lin D, et al. Clinical parameter and Th17 related to lymphocytes infiltrating degree of labial salivary gland in primary Sjö gren’s syndrome. Clin Rheumatol. 2014;33:523-9. doi: 10.1007/s10067-013-2476-z

122. Sakai A, Sugawara Y, Kuroishi T, et al. Identification of IL-18 and Th17 cells in salivary glands of patients with Sjö gren’s syndrome, and amplification of IL-17-mediated secretion of inflammatory cytokines from salivary gland cells by IL-18. J Immunol. 2008;181:2898-906. doi: 10.4049/jimmunol.181.4.2898

123. Katsifis GE, Rekka S, Moutsopoulos NM, et al. Systemic and local interleukin-17 and linked cytokines associated with Sjö gren's syndrome immunopathogenesis. Amer J Pathol. 2009;175:1167-77. doi: 10.2353/ajpath.2009.090319

124. Ciccia F, Guggino G, Rizzo A, et al. Potential involvement of IL-22 and IL-22-producing cells in the inflamed salivary glands of patients with Sjö gren’s syndrome. Ann Rheum Dis. 2012;71:295-301. doi: 10.1136/ard.2011.154013

125. Alunno A, Carubbi F, Caterbi S, et al. The role of T helper 17 cell subsets in Sjö gren’s syndrome: similarities and differences between mouse model and humans. Ann Rheum Dis. 2014;73:e42. doi: 10.1136/annrheumdis-2014-205517

126. Lavoie TN, Stewart CM, Berg KM, et al. Expression of interleukin-22 in Sjö gren’s syndrome: significant correlation with disease parameters. Scand J Immunol. 2011;74:377- 82. doi: 10.1111/j.1365-3083.2011.02583.x

127. Li L, He J, Zhu L, et al. Clinical relevance of IL-17-producing CD4+CD161+ cell and its subpopulations in primary Sjö gren’s syndrome. J Immunol Res. 2015; Article ID 307453. doi: 10.1155/2015/307453

128. Корсакова ЮЛ, Станислав МЛ, Денисов ЛН, Насонов ЕЛ. Устекинумаб – новый препарат для лечения псориаза и псориатического артрита. Научно-практическая ревматология. 2013;51(2):170-81 [Korsakova YL, Stanislav ML, Denisov LN, Nasonov EL. Ustekinumab is a new drug to treat psoriasis and psoriatic arthritis. Nauchno- Prakticheskaya Revmatologiya = Rheumatology Science and Practice. 2013;51(2):170-80 (In Russ.)]. doi: 10.14412/1995-4484-2013-646

129. Hueber W, Patel D, Dryja T, et al. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010;2:52ra72. doi: 10.1126/scitranslmed.3001107

130. Patel DD, Lee DM, Kolbinger F, Antoni C. Effect of IL-17A blockade with secukinumab in autoimmune diseases. Ann Rheum Dis. 2013;72 Suppl 2:ii116–ii123. doi: 10.1136/annrheumdis-2012-202371

131. Papp KA, Langley RG, Sigurgeirsson B, et al. Efficacy and safety of secukinumab in the treatment of moderate-to-severe plaque psoriasis: a randomized, double-blind, placebo- controlled phase II dose-ranging study. Br J Dermatol. 2013;168:412-21. doi: 10.1111/bjd.12110

132. Langley RG, Elewski BE, Lebwohl M, et al; ERASURE Study Group, FIXTURE Study Group. Secukinumab in plaque psoriasis – results of two phase 3 trials. N Engl J Med. 2014;371:326-38. doi: 10.1056/NEJMoa1314258

133. Blauvelt A, Prinz JC, Gottlieb AB, et al; FEATURE Study Group. Secukinumab administration by pre-filled syringe: efficacy, safety and usability results from a randomized controlled trial in psoriasis (FEATURE). Br J Dermatol. 2015;172:484-93.

134. Blauvelt A, Reich K, Tsai TF, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate-to-severe plaque psoriasis up to 1 year: Results from the CLEAR study. J Am Acad Dermatol. 2016 Sep 20. pii: S0190-9622(16)30624-7. doi: 10.1016/j.jaad.2016.08.008

135. McInnes IB, Sieper J, Braun J, et al. Efficacy and safety of secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe psoriatic arthritis: a 24- week, randomised, double-blind, placebo-controlled, phase II proof-of- concept trial. Ann Rheum Dis. 2014;73:349-56. doi: 10.1136/annrheumdis-2012-202646

136. Mease PJ, McInnes IB, Kirkham B, et al; FUTURE 1 Study Group. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373:1329-39. doi: 10.1056/NEJMoa1412679

137. McInnes IB, Mease PJ, Kirkham B, et al; FUTURE 2 Study Group. Secukinumab, a human anti-interleukin-17A monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2015;386:1137-46. doi: 10.1016/S0140-6736(15)61134-5

138. Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab provides sustained improvements in psoriatic arthritis: 2-year efficacy and safety results from a phase 3 randomized, doubleblind, placebo-controlled trial [abstract]. Arthritis Rheum. 2015;67 Suppl 10.

139. Kavanaugh A, McInnes IB, Mease PJ, et al. Efficacy of subcutaneous secukinumab in patients with active psoriatic arthritis stratified by prior tumor necrosis factor inhibitor use: Results from the randomized placebo-controlled FUTURE 2 study. J Rheumatol. June 15 2016. doi: 10.3899/ jrheum.160275

140. Strand V, Husni ME, Reichmann W, et al. Network meta-analysis of tumor necrosis factor, interleukins, and phosphodiesterase-4 inhibitor in the treatment of psoriatic arthritis. Arthritis Rheum. 2015;67 Suppl. 10.

141. Ungprasert P, Thongprayoon C, Davis JM 3rd. Indirect comparisons of the efficacy of subsequent biological agents in patients with psoriatic arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis. Clin Rheumatol. 2016;35:1795-803. doi: 10.1007/s10067-016-3204-2

142. McInnes IB, Nash P, Ritchlin C, et al. Secucinumab for the treatment of psoriatic arthritis: comparative effectiveness results versus licensed biologics and apremilast from a network metaanalysis. Ann Rheum Dis. 2016;75:348-349. doi: 10.1136/annrheumdis-2016-eular.1716

143. Baeten D, Baraliakos X, Braun J, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo- controlled trial. Lancet. 2013;382:1705-13. doi: 10.1016/S0140-6736(13)61134-4

144. Baeten D, Sieper J, Braun J, et al. Secukinumab, an interleukin-17a inhibitor, in ankylosing spondylitis. N Engl J Med. 2015;373:2534-48 doi: 10.1056/NEJMoa1505066

145. Baeten D, Braun J, Sieper J, et al. Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis: 2-year efficacy and safety results from a phase 3, randomized, double-blind, placebo-controlled trial [abstract]. Arthritis Rheum. 2015;67 Suppl 10.

146. Braun J, Deodhar AA, Sieper J, et al. Secukinumab significantly improves signs and symptoms of active ankylosing spondylitis: 52-week results from a randomized, double- blind, placebo-controlled phase 3 trial with subcutaneous loading and maintenance dosing [abstract]. Arthritis Rheum. 2015;67 Suppl 10.

147. Baeten D, Blanco R, Geusens P, et al. Secukinumab provides sustained improvements in the signs and symptoms of active ankylosing spondylitis in anti-TNF-naive patients and those previously exposed to anti-TNF therapy: 52-week results from two randomized, double-blind, placebo-controlled phase 3 trials [abstract]. Arthritis Rheum. 2015;67 Suppl 10.

148. Sieper J, Deodhar A, Marzo-Ortega H, et al; MEASURE 2 Study Group. Secukinumab efficacy in anti-TNF-naive and anti-TNFexperienced subjects with active ankylosing spondylitis: results from the MEASURE 2 Study. Ann Rheum Dis. 2016 Aug 31. pii: annrheumdis-2016-210023. doi: 10.1136/annrheumdis-2016-210023

149. Baraliakos X, Borah B, Braun J, et al. Long-term effects of secukinumab on MRI findings in relation to clinical efficacy in subjects with active ankylosing spondylitis: an observational study. Ann Rheum Dis. 2016;75:408-12. doi: 10.1136/annrheumdis- 2015-207544

150. Baraliakos X, Deodhar A, Braun J, et al. Effect of interleukin-17A inhibition on spinal radiographic changes through 2 years in patients with active ankylosing spondylitis: results of a phase 3 study with secukinumab [abstract]. Arthritis Rheum. 2015;67 Suppl 10.

151. Genovese M, Durez P, Richards H, et al. Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study. Ann Rheum Dis. 2013;72:863-9. doi: 10.1136/annrheumdis- 2012-201601

152. Genovese MC, Durez P, Richards HB, et al. One-year efficacy and safety results of secukinumab in patients with rheumatoid arthritis: phase II, dose-finding, double-blind, randomized, placebo-controlled study. J Rheumatol. 2014;41:414-21. doi: 10.3899/jrheum.130637

153. Tlustochowicz W, Rahman P, Seriolo B, et al. Efficacy and safety of subcutaneous and intravenous loading dose regimens of secukinumab in patients with active rheumatoid arthritis: results from a randomized phase II study. J Rheumatol. 2016;43:495-503. doi: 10.3899/jrheum.150117

154. Burmester GR, Durez P, Shestakova G, et al. Association of HLA-DRB1 alleles with clinical responses to the anti-interleukin- 17A monoclonal antibody secukinumab in active rheumatoid arthritis. Rheumatology (Oxford). 2016;55:49-55. doi: 10.1093/rheumatology/kev258

155. De Almeida DE, Ling S, Holoshitz J. New insights into the functional role of the rheumatoid arthritis shared epitope. FEBS Lett. 2011;585:3619-26. doi: 10.1016/j.febslet.2011.03.035

156. Koenders MI, Marijnissen RJ, Joosten LA, et al. T cell lessons from the rheumatoid arthritis synovium SCID mouse model: CD3-rich synovium lacks response to CTLA-4Ig but is successfully treated by interleukin-17 neutralization. Arthritis Rheum. 2012;64:1762-70. doi: 10.1002/art.34352

157. Sugita S, Kawazoe Y, Imai A, et al. Inhibition of Th17 differentiation by anti-TNF-alpha therapy in uveitis patients with Behcet’s disease. Arthr Res Ther. 2012;14:R99. doi: 10.1186/ar3824

158. Brand S. Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut. 2009;58:1152-67. doi: 10.1136/gut.2008.163667

159. Sarra M, Pallone F, MacDonald TT, Monteleone G. IL-23/IL-17 axis in IBD. Inflamm Bowel Dis. 2010;16:1808-13. doi: 10.1002/ibd.21248

160. Hueber W, Sands BE, Lewitzky S, et al; Secukinumab in Crohn’s Disease Study Group. Secukinumab, a human anti-IL-17A monoclonal antibody, for moderate to severe Crohn’s disease: unexpected results of a randomised, double-blind placebo-controlled trial. Gut. 2012;61:1693-700. doi: 10.1136/gutjnl-2011-301668

161. Targan SR, Feagan BG, Vermeire S, et al. A randomized, doubleblind, placebo- controlled study to evaluate the safety, tolerability, and efficacy of AMG 827 in subjects with moderate to severe Crohn’s disease. Gastroenterology. 2012;143:E26. doi: 10.1053/j.gastro.2012.07.084

162. O’Connor W Jr, Zenewicz LA, Flavell RA. The dual nature of T(H)17 cells: shifting the focus to function. Nat Immunol. 2010;11:471-6. doi: 10.1038/ni.1882

163. Blauvelt A. Safety of secukinumab in the treatment of psoriasis. Expert Opin Drug Safe. 2016;15:1413-20. doi: 10.1080/14740338.2016.1221923

164. Mease PJ, McInnes IB, Gottlieb AB, et al. Secukinumab safety and tolerability in patients with active psoriatic arthritis and psoriasis: Results from a pooled safety analysis [abstract]. Arthritis Rheum. 2015;67 Suppl 10.

165. Schett G, Elewaut D, McInnes IB, et al. How cytokine networks fuel inflammation: Toward a cytokine-based disease taxonomy. Nat Med. 2013;19:822-4. doi: 10.1038/nm.3260

166. McInnes IB, Buckley CD, Isaacs JD. Cytokines in rheumatoid arthritis – shaping the immunological landscape. Nat Rev Rheumatol. 2016;12:63-8. doi: 10.1038/nrrheum.2015.171

167. Mease PJ, Gottlieb AB, Berman A, et al. The efficacy and safety of clazakizumab, an anti-interleukin-6 monoclonal antibody, in a phase IIb study of adults with active psoriatic arthritis. Arthritis Rheum. 2016;68(9):2163-73. doi: 10.1002/art.39700

168. Koenders MI, Marijnissen RJ, Devesa I, et al. Tumor necrosis factor-interleukin-17 interplay induces S100A8, interleukin-1β, and matrix metalloproteinases, and drives irreversible cartilage destruction in murine arthritis: rationale for combination treatment during arthritis. Arthritis Rheum. 2011;63:2329-39. doi: 10.1002/art.30418

169. Zwerina K, Koenders M, Hueber A, et al. Anti IL-17A therapy inhibits bone loss in TNF-α- mediated murine arthritis by modulation of the T-cell balance. Eur J Immunol. 2012;42:413- 23. doi: 10.1002/eji.201141871

170. Notley CA, Inglis JJ, Alzabin S, et al. Blockade of tumor necrosis factor in collagen- induced arthritis reveals a novel immunoregulatory pathway for TH1 and TH17 cells. J Exp Med. 2008;205:2491-7. doi: 10.1084/jem.20072707

171. Van Hamburg JP, Asmawidjaja PS, Davelaar N, et al. TH17 cells, but not TH1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum. 2011;63:73-83. doi: 10.1002/art.30093

172. Aerts NE, de Knop KJ, Leysen J, et al. Increased IL-17 production by peripheral T helper cells after tumour necrosis factor blockade in rheumatoid arthritis is accompanied by inhibition of migration-associated chemokine receptor expression. Rheumatology (Oxford). 2010;49:2264-72. doi: 10.1093/rheumatology/keq224

173. Taylor PC, Williams RO. Combination cytokine blockade: the way forward in therapy for rheumatoid arthritis. Arthritis Rheum. 2015;67:14-6. doi: 10.1002/art.38893

174. Kontermann RE, Brinkman U. Bispecific antibodies. Drug Discov Today. 2015;20:838-47. doi: 10.1016/j.drudis.2015.02.008

175. Fischer JA, Hueber AJ, Wilson S, et al. Combined inhibition of tumor necrosis factor α and interleukin-17 as a therapeutic opportunity in rheumatoid arthritis: development and characterization of a novel bispecific antibody. Arthritis Rheum. 2015;67:51-62. doi: 10.1002/art.38896

176. Kalden JR. Emerging therapies for rheumatoid arthritis. Rheumatol Ther. 2016;3:31-42. doi: 10.1007/s40744-016-0032-4


Для цитирования:


Насонов Е.Л. Новые возможности фармакотерапии иммуновоспалительных ревматических заболеваний: фокус на ингибиторы интерлейкина 17. Научно-практическая ревматология. 2017;55(1):68-86. https://doi.org/10.14412/1995-4484-2017-68-86

For citation:


Nasonov E.L. NEW POSSIBILITIES OF PHARMACOTHERAPY FOR IMMUNOINFLAMMATORY RHEUMATIC DISEASES: A FOCUS ON INHIBITORS OF INTERLEUKIN-17. Rheumatology Science and Practice. 2017;55(1):68-86. (In Russ.) https://doi.org/10.14412/1995-4484-2017-68-86

Просмотров: 1201


Creative Commons License
Контент доступен под лицензией Creative Commons Attribution 4.0 License.


ISSN 1995-4484 (Print)
ISSN 1995-4492 (Online)