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Научно-практическая ревматология

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Современный взгляд на патогенез спондилоартритов – молекулярные механизмы

https://doi.org/10.14412/1995-4484-2015-299-307

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Аннотация

В настоящее время одним из основных звеньев патогенеза спондилоартритов (СпА) считается нарушение иммунного гомеостаза слизистой оболочки кишечника у генетически предрасположенных лиц, что приводит к развитию системного хронического воспаления. Результаты исследований последних лет позволяют говорить о ключевой роли оси интерлейкин 23/интерлейкин 17 (ИЛ23/ИЛ17) в развитии этих заболеваний. Многофакторные звенья патогенеза СпА характеризуются не только гиперпродукцией ИЛ23, но и изменением чувствительности к этому цитокину клеток-мишеней с параллельным увеличением их числа, что приводит к хроническому аутовоспалительному процессу, который реализуется через широкий спектр клинических проявлений различных вариантов СпА.

Об авторах

Е. Л. Насонов
ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34А
Россия


Е. А. Галушко
ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34А
Россия

заведующая учебно-методическим отделом с центром информационных технологий ФГБНУ НИИР им. В.А. Насоновой, докт. мед. наук



А. В. Гордеев
ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва, Россия 115522 Москва, Каширское шоссе, 34А
Россия

профессор, ведущий научный сотрудник лаборатории микроциркуляции
ФГБНУ НИИР им. В.А. Насоновой, докт. мед. наук



Список литературы

1. 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 arget 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

2. Эрдес ШФ. Развитие концепции спондилоартритов. Научно-практическая ревматология. 2014;52(5):474–6 [Erdes ShF. Spondyloarthritis: Evolution of a concept. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2014;52(5):474–6 (In Russ.)]. doi: 10.14412/1995-4484-2014-474-476

3. Ребров АП, Гайдукова ИЗ. Комментарии к статье «Ранняя дигностика анкилозирующего спондилита», опубликованной в №4 за 2013 г. Научно-практическая ревматология. 2014;52(2):228–9 [Rebrov AP, Gaidukova IZ. Comments on the article «Early diagnosis of ankylosing spondylitis» published in №4, 2013. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2014;52(2):228–9 (In Russ.)]. doi: 10.14412/1995-4484-2014-228-229

4. Jacques P, van Praet L, Carron P, et al. Pathophysiology and role of the gastrointestinal system in pondyloarthritides. Rheum Dis Clin North Am. 2012 Aug;38(3):569–82. doi: 10.1016/j.rdc.2012.08.012

5. Peluso R, Di Minno MN, Iervolino S, et al. Enteropathic spondyloarthritis: from diagnosis to treatment. Clin Dev Immunol. 2013;2013:631408. doi: 10.1155/2013/631408

6. Colombo E, Latiano A, Palmieri O, et al. Enteropathic spondyloarthropathy: a common genetic background with inflammatory bowel disease? World J Gastroenterol. 2009 May 28;15(20):2456–62. doi: 10.3748/wjg.15.2456

7. Schaeverbeke T, Truchetet ME, Richez C. Gut metagenome and spondyloarthritis. Joint Bone Spine. 2013 Jul;80(4):349–52. doi: 10.1016/j.jbspin.2013.02.005

8. Lakatos P.L. Pathogenesis of IBD. World J Gastroenterol. 2006;12(12):235–40.

9. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–73. doi: 10.1146%2Fannurev.iy.07.040189.001045

10. Zhu S, Qian Y. IL-17/IL-17 receptor system in autoimmune disease: mechanisms and therapeutic potential. Clin Sci. 2012;122(11):487–511. doi: 10.1042%2FCS20110496

11. Gaffen SL. Structure and signalling in the IL-17 receptor family. Nat Rev Immunol. 2009;9(8):556–67. doi: 10.1038%2Fnri2586

12. Kimura A, Kishimoto T. IL 6: regulator of Treg/Th17 balance. Eur J Immunol. 2010;40(7):1830–5. doi: 10.1002%2Feji.201040391

13. Van Praet L, van den Bosch FE, Jacques P, et al. Microscopic gut inflammation in axial spondyloarthritis: a multiparametric predictive model. Ann Rheum Dis. 2013;72(3):414–7. doi: 10.1136/annrheumdis-2012-202135

14. Sherlock JP, Cua DJ. Interleukin-23: a promising therapeutic target in seronegative spondyloarthropathy. Curr Opin Pharmacol. 2013 Jun;13(3):445–8. doi: 10.1016/j.coph.2013.03.002

15. Sherlock JP, Joyce-Shaikh B, Turner SP, et al. IL-23 induces spondyloarthropathy by acting on ROR-βt+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012 Jul 1;18(7):1069–76. doi: 10.1038/nm.2817

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

17. Wendling D, Guillot X, Prati C. The IL-23/Th-17 pathway in spondyloarthritis: The Royal Road? Joint Bone Spine. 2014 Sep 19. pii: S1297-319X(14)00195-X. doi: 10.1016/j.jbspin.2014.08.003

18. Mielants H, Veys EM, Cuvelier C, et al. The evolution of spondyloarthropathies in relation to gut histology. II. Histological aspects. J Rheumatol. 1995;22:2273–8.

19. 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

20. Mielants H, Veys E, Cuvelier C, de Vos M. Course of gut inflammation in spondylarthropathies and therapeutic consequences. Baillieres Clin Rheumatol. 1996;10:147–64. doi: 10.1016/S0950-3579(96)80010-0

21. Simenon G, van Gossum A, Adler M, et al. Macroscopic and microscopic gut lesions in seronegative spondyloarthropathies. J Rheumatol. 1990;17:1491–4.

22. Ciccia F, Accardo-Palumbo A, Giardina A, et al. Expansion of intestinal CD4+CD25(high) Treg cells in patients with ankylosing spondylitis: a putative role for interleukin-10 in preventing intestinal Th17 response. Arthritis Rheum. 2010;62:3625–34. doi: 10.1002/art.27699

23. Maloy K. IL-23 / IL-17 axis in intestinal inflammation. J Internal Med. 2008;263:584–90. doi: 10.1111/j.1365-2796.2008.01950.x

24. Jacques P, Elewaut D. Joint expedition: linking gut inflammationto arthritis. Mucosal Immunol. 2008;1:364–71. doi: 10.1038/mi.2008.24

25. Cuvelier C, Barbatis C, Mielants H, et al. Histopathology of intestinal inflammation related to reactive arthritis. Gut. 1987;28:394–401. doi: 10.1136/gut.28.4.394

26. Miossec P, Korn T, Kuchroo VK. Interleukin17 and type 17 helper T cells. N EnglJ Med. 2009;361:888–98. doi: 10.1056/NEJMra0707449

27. Tang C, Chen S, Qian H, et al. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2011;135:112–24. doi: 10.1111/j.1365-2567.2011.03522.x

28. Esin S, Batoni G, Counoupas C, et al. Direct binding of human NK cell natural cytotoxicity receptor NKp44 to the surfaces of mycobacteria and other bacteria. Infect Immun. 2008;76(4):1719e27.

29. Turner JE, Stockinger B, Helmby H. IL-22 mediates goblet cell hyperplasia and worm expulsion in intestinal helm in the infection. PLoS Pathog. 2013;9(10):e1003698. doi: 10.1371/journal.ppat.1003698

30. Gaston JS, Goodall JC, Baeten D. Interleukin-23: a central cytokine in the pathogenesis of spondylarthritis. Arthritis Rheum. 2011;63:3668–71. doi: 10.1002/art.30600

31. Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010;330:1768–73. doi: 10.1126/science.1195568

32. Wing K, Sakaguchi S. Regulatory T cells exert checks and balances on self tolerance and autoimmunity. Nat Immunol. 2010;11:7–13. doi: 10.1038/ni.1818

33. Leirisalo-Repo M. Prognosis, course of disease, and treatment of the spondyloarthropathies. Rheum Dis Clin North Am. 1998;24(4):737e51.

34. Merilahti-Palo R, Soderstrom KO, Lahesmaa-Rantala R, et al. Bacterial antigens in synovial biopsy specimens in Yersinia triggered reactive arthritis. Ann Rheum Dis. 1991;50(2):87e90.

35. Geczy AF, Alexander K, Bashir HV, et al. A factor(s) in Klebsiella culture filtrates specifically modifies an HLA-B27 associated cellsurface component. Nature. 1980;283(5749):782e4.

36. Hammer RE, Maika S.D, Richardson J.A, et al. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human 2m: an animal model of HLA-B27-associated human disorders. Cell. 1990;63(5):1099–112. doi: 10.1016/0092- 8674(90)90512-D

37. Taurog JD, Richardson JA, Croft JT, et al. The germfree state prevents development of gut and joint inflammatory disease in HLAB27 transgenic rats. J Exper Med. 1994;180(6): 2359–64. doi: 10.1084/jem.180.6.2359

38. Scher JU, Sczesnak A, Longman RS, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife. 2013;2:e01202. doi: 10.7554/eLife.01202

39. Ge S, He Q, Granfors K. HLA-B27 modulates intracellular growth of Salmonella pathogenicity island 2 mutants and production of cytokines in infected monocytic U937 cells. PLoS One. 2012;7(3):e34093. doi: 10.1371/journal.pone.0034093

40. Stebbings S, Munro K, Simon MA, et al. Comparison of the fecal microflora of patients with ankylosing spondylitis and controls using molecular methods of analysis. Rheumatology (Oxford). 2002;41(12):1395e401.

41. Rashid T, Ebringer A. Ankylosing spondylitis is linked to Klebsiella – the evidence. Clin Rheumatol. 2007;26(6): 858e64.

42. Rashid T, Wilson C, Ebringer A. The link between ankylosing spondylitis, Crohn’s disease, Klebsiella, and starch consumption. Clin Dev Immunol. 2013;(8):726–32. doi: 10.1155/2013/872632

43. Taurog JD, Rival C, van Duivenvoorde LM, et al. Autoimmune epididymoorchitis is essential to the pathogenesis of male-specific spondylarthritis in HLA-B27-transgenic rats. Arthritis Rheum. 2012;64:2518–28. doi: 10.1002/art.34480

44. Каратеев АЕ, Галушко ЕА. Поражение кишечника у больных спондилоартритами. Научно-практическая ревматология. 2015;53(2):190–9 [Karateev AE, Galushko EA. Bowel involvement in patients with spondyloarthritis. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2015;53(2):190–9 (In Russ.)]. doi: 10.14412/1995-4484-2015- 190-199

45. Kleizen B, Braakman I. Protein folding and quality control in the endoplasmic reticulum. Curr Opin Cell Biol. 2004;16:343–9. doi: 10.1016/j.ceb.2004.06.012

46. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediatirs of endoplasmic reticulum stresss-induced apoptosis. EMBO Rep. 2006;7(9):880–5. doi: 10.1038/sj.embor.7400779

47. Kitamura M. Endoplasmic reticulum stress and unfolded protein response in renal pathophysiology: Janus faces. Am J Physiol Renal Physiol. 2008;295(2):F323–F334. doi: 10.1152/ajprenal. 00050.2008

48. 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

49. Colbert RA, Tran TM, Layh-Schmitt G. HLA-B27 misfolding and ankylosing spondylitis. Mol Immunol. 2014;57(1):44e51.

50. Kaser A, Adolph TE, Blumberg RS. The unfolded protein response and gastrointestinal disease. Semin Immunopathol. 2013;35(3):307e19.

51. Hacquard-Bouder C, Ittah M, Breban M. Animal models of HLA-B27-associated diseases: new outcomes. Joint Bone Spine. 2006;73:132–8. doi: 10.1016/j.jbspin.2005.03.016

52. Bodor M, Kelly EJ, Ho RJ. Characterization of the human MDR1 gene. AAPS J. 2005;7:E1–E5. doi: 10.1208/aapsj070101

53. Abcouwer SF, Marjon PL, Loper RK, Vander Jagt DL. Response of VEGF expression to amino acid deprivation and inducers of endoplasmic reticulum stress. Invest Ophthalmol Vis Sci. 2002;43:2791–8.

54. Ciccia F, Accardo-Palumbo A, Rizzo A, et al. Evidence that autophagy, but not the unfolded protein response, regulates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation. Ann Rheum Dis. 2013;73(8):1566e74.

55. Benjamin JL, Sumpter Jr R, Levine B, et al. Intestinal epithelial autophagy is essential for host defense against invasive bacteria. Cell Host Microbe. 2013;13(6):723e34.

56. Menendez-Benito V. Autophagy in MHC class II presentation: sampling from within. Immunity. 2007;26:1–3. doi: 10.1016/j.immuni.2007.01.005

57. Duan Z, Pan F, Zeng Z, et al. Interleukin-23 receptor genetic polymorphisms and ankylosing spondylitis susceptibility: a metaanalysis. Rheumatol Int. 2012;32:1209–14. doi: 10.1007/s00296-010-1769-7

58. Burton P, Clayton D, Cardon L, et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet. 2007;39:1329–37. doi: 10.1038/ng.2007.17

59. Reveille JD, Sims A-M, 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

60. Di Meglio P, di Cesare A, Laggner U, et al. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans. PLoS ONE 2011;6:e17160. doi: 10.1371/journal.pone.0017160

61. Coffre M, Roumier M, Rybczynska M. Combinatorial control of Th17 and Th1 cell functions by genetic variations in genes associated with the interleukin-23 signaling pathway in spondyloarthritis. Arthritis Rheum. 2013 Jun;65(6):1510–21. doi: 10.1002/art.37936

62. Гордеев АВ, Галушко ЕА, Насонов ЕЛ. Концепция мультиморбидности в ревматологической практике. Научно- практическая ревматология. 2014;52(4):362–5 [Gordeev AV, Galushko EA, Nasonov EL. The concept of multimorbidity in rheumatologic practice. Nauchno-prakticheskaya revmatologiya = Rheumatology Science and Practice. 2014;52(4):362–5 (In Russ.)]. doi: 10.14412/1995-4484-2014-362-365

63. Onishi RM, Gaffen SL. Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease. Immunology. 2010;129(3):311–21. doi: 10.1111%2Fj.1365-2567.2009.03240.x

64. Adamopoulos I, Chao C, Geissler R, et al. Interleukin-17A upregulates receptor activator of NF-κB on osteoclast precursors. Arthritis Res Ther. 2010;12(1):R29. doi: 10.1186%2Far2936

65. Sato K, Suematsu A, Okamoto K, et al. Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med. 2006;203(12):2673–82. doi: 10.1084%2Fjem.20061775

66. Suurmond J, Dorjee A, Boon M, et al. Mast cells are the main interleukin 17-positive cells in anticitrullinated protein antibodypositive and -negative rheumatoid arthritis and osteoarthritis synovium. Arthritis Res Ther. 2011;13(5):R150. doi: 10.1186%2Far3466

67. Wendling D. IL-23 and IL-17 in ankylosing spondylitis. Rheumatol Int. 2010;30:1547. doi: 10.1007/s00296-009-1226-7

68. Chen WS, Chang YS, Lin KC, et al. Association of serum interleukin-17 andinterleukin-23 levels with disease activity in Chinese patients with ankylosingspondylitis. J Chin Med Assoc. 2012;75:303–8. doi: 10.1016/j.jcma.2012.05.006

69. McInnes IB, Kavanaugh A, Gottlieb AB, et al. Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1-year results of the phase3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet. 2013;382:780–9. doi: 10.1016/S0140-736(13)60594-2

70. Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional nonbiological and biological anti-tumor necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, doubleblind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73:990–9. doi: 1136/annrheumdis-2013-204655

71. Poddubnyy D, Hermann KG, Callhoff J, et al. Ustekinumab for the treatment ofpatients with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof of concept study (TOPAS). Ann Rheum Dis. 2014;73:817–23. doi: 10.1136/annrheumdis-2013-204248

72. 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-ofconcept trial. Ann Rheum Dis. 2014;73:349–56. doi: 10.1136/annrheumdis-2012-202646

73. 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


Для цитирования:


Насонов Е.Л., Галушко Е.А., Гордеев А.В. Современный взгляд на патогенез спондилоартритов – молекулярные механизмы. Научно-практическая ревматология. 2015;53(3):299-307. https://doi.org/10.14412/1995-4484-2015-299-307

For citation:


Nasonov E.L., Galushko E.A., Gordeev A.V. MODERN IDEA ON THE PATHOGENESIS OF SPONDYLOARTHRITIS: MOLECULAR MECHANISMS. Rheumatology Science and Practice. 2015;53(3):299-307. (In Russ.) https://doi.org/10.14412/1995-4484-2015-299-307

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