Some aspects of pathogenesis of ankylosing spondylitis


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Abstract

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the spine (spondylitis) and sacroiliac joints (sacroileitis) associated in many cases with inflammatory affection of the peripheral joints (arthritis), entesises (entesitis), eyes (uveitis), intestine (enteritis) and aortic root (aortitis). AS is considered now as a prototype of diseases from the group of seronegative spondyloarthritis. AS is a hereditary disease. Predisposition to AS (90%) is associated with genetic factors the key gene of which is HLA-B27. As pathogenesis of AS is not still verified, three hypotheses are considered basing on HLA-B27 biology.The role of environmental factors involved in AS development (tension in enteses and infection) are discussed.

About the authors

Shandor Erdes

Email: erdes@irramn.ru

Sh Erdes

Research Institute of Rheumatology of the Academy of Medical Sciences, Moscow

Research Institute of Rheumatology of the Academy of Medical Sciences, Moscow

References

  1. Sieper J., Rudwaleit M., Khan M. A., Braun J. Concepts and epidemiology of spondyloarthritis. Best Pract. Res. Clin. Rheumatol. 2006; 20: 401-417.
  2. Беленький А. Г. Энтезопатии при серонегативных спондилоартритах. Consilium Medicum 2006; 8: 12-16.
  3. Goh L., Samanta A. A systematic MeDLiNe analysis of therapeutic approaches in ankylosing spondylitis. Rheumatol. Int. 2009; 29: 1123-1135.
  4. McLeod C. et al. Adalimumab, etanercept and infliximab for the treatment of ankylosing spondylitis: a systematic review and economic evaluation. Hlth Technol. Assess. 2007; 11: 1- 158, iii-iv.
  5. Zochling J. et al. ASAS/eULAR recommendations for the management of ankylosing spondylitis. Ann. Rheum. Dis. 2006; 65: 442-452.
  6. Schett G., Landewé R., van der Heijde D. Tumour necrosis factor blockers and structural remodelling in ankylosing spondylitis: what is reality and what is fiction? Ann. Rheum. Dis. 2007; 66: 709-711.
  7. van der Heijde D. et al. Radiographic findings following two years of infliximab therapy in patients with ankylosing spondylitis. Arthr. and Rheum. 2008; 58: 3063-3070.
  8. van der Heijde D. et al. Radiographic progression of ankylosing spondylitis after up to two years of treatment with etanercept. Arthr. and Rheum. 2008; 58: 1324-1331.
  9. van der Heijde D., Salonen D., Weissman B. N. et al. Assessment of radiographic progression in the spines of patients with ankylosing spondylitis treated with adalimumab for up to 2 years. Arthr. Res. Ther. 2009; 11: R127.
  10. Cawley M. I., Chalmers T. M., Kellgren J. H., Ball J. Destructive lesions of vertebral bodies in ankylosing spondylitis. Ann. Rheum. Dis. 1972; 31: 345-358.
  11. Appel H. et al. Immunohistologic analysis of zygapophyseal joints in patients with ankylosing spondylitis. Arthr. and Rheum. 2006; 54: 2845-2851.
  12. Appel H. et al. Immunohistochemical analysis of hip arthritis in ankylosing spondylitis: evaluation of the bone-cartilage interface and subchondral bone marrow. Arthr. and Rheum. 2006; 54: 1805-1813.
  13. Francois R. J., Neure L., Sieper J., Braun J. Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann. Rheum. Dis. 2006; 65: 713-720.
  14. Maksymowych W. P., Chiowchanwisawakit P., Clare T. et al. Inflammatory lesions of the spine on magnetic resonance imaging predict the development of new syndes mophytes in ankylosing spondylitis: evidence of a relationship between inflammation and new bone formation. Arthr. and Rheum. 2009; 60: 93-102.
  15. McGonagle D., Wakefied R. J., Tan A. L. et al. District topography of erosion and new bone formation in Achilles tendon enthesits: Implications for understanding the link between inflammation and bone formation in spondyloarthritis. Arthr. and Rheum. 2008; 58; 2964-2969.
  16. Benjamin M., McGonagle D. The anatomical basis for disease localisation in seronegative spondyloarthropathy at entheses and related sites. J. Anat. 2001; 199; 503-506.
  17. Benjamin M., McGonagle D. The enthesis organ concept and its relevance to the spondyloarthropathies. Adv. Exp. Med. Biol. 2009; 649: 57-70.
  18. Brown M. A. et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthr. and Rheum. 1997; 40: 1823-1828.
  19. Brown M. A., Laval S. H., Brophy S., Calin A. Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis. Ann. Rheum. Dis. 2000; 59: 883-886.
  20. Burton P. R. et al. Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat. Genet. 2007; 39: 1329-1337.
  21. Australo-Anglo-American Spondyloarthritis consortium (TASC); Reveille J. D. et al. Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nat. Genet. 2010; 42: 123-127.
  22. Choi C., Kim T., Jun J. et al. ARTS1 polymorphisms are associated with ankylosing spondylitis in Koreans. Ann. Rheum. Dis. 2010; 69: 582-584.
  23. Cui X., Rouhani F. N., Hawari F., Levine S. J. An aminopeptidase, ARTS-1, is required for inter1eukin-6 receptor shedding. J. Biol. Chem. 2003; 278: 28677-28685.
  24. Thomas G. P., Brown M. A. Genetics and genomics of ankylosing spondylitis. Immunol. Rev. 2010; 233: 162-180.
  25. Layh-Schmitt G., Colbert R. A. The interleukin-23/interleukin-17 axis in spondyloarthritis. Curr. Opin. Rheumatol. 2008; 20: 392-397.
  26. van den Berg W. B., Miossec P. iL-17 as a future therapeutic target for rheumatoid arthritis. Nat. Rev. Rheumatol. 2009; 5: 549-553.
  27. Genovese M. C. et al. LY2439821, a humanized anti-iL-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis. Arthr. and Rheum. 2010; 62: 929-939.
  28. Palodini F., Belfiore F., Cocco E. et al. HLA-E gene polymorphism associates with ankylosing spondylitis. Arthr. Res. Ther. 2009; 11: R171 (doi:10.1186ar 2860).
  29. Lopez-Larrea C., Blanko-Gelaz M. A., Torre-Alonzo J. C. Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian population. Arthr. Res. Ther. 2006; 8: R101 (doi 10.1186a/ar1988).
  30. Khan M. A. Epidemiology of HLA-B27 and arthritis. Clin. Rheumatol. 1996; 15 (Suppl. 1): 10-12.
  31. Hammer R. E., Maika S. D., Richardson J. A. et al. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell 1990; 63; 1099-1112.
  32. Milia A. F. et al. HLA-B27 transgenic rat: an animal model mimicking gut and joint involvement in human spondyloarthritides. Ann. N. Y. Acad. Sci. 2009; 1173: 570-574.
  33. Taurog J. D. et al. Inflammatory disease in HLA-B27 transgenic rats. Immunol. Rev. 1999; 169: 209-223.
  34. Brown M. A. Genetics and the pathogenesis of ankylosing spondylitis. Curr. Opin. Rheumatol. 2009; 21: 318-323.
  35. Reveille J. D. Recent studies on the genetic basis of ankylosing spondylitis. Curr. Rheumatol. Rep. 2009; 11: 340-348.
  36. Reveille J. D., Maganti R. M. Subtypes of HLA-B27: history and implications in the pathogenesis of ankylosing spondylitis. Adv. Exp. Med. Biol. 2009; 649: 159-176.
  37. Brewerton D. A. et al. Ankylosing spondylitis and HL-A 27. Lancet 1973; 1: 904-907.
  38. Schlosstein L., Terasaki P. I., Bluestone R., Pearson C. M. High association of an HL-A antigen, W27, with ankylosing spondylitis. N. Engl. J. Med. 1973; 288: 704-706.
  39. Feldmann M., Maini S. R. Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeutics. Immunol. Rev. 2008; 223: 7-19.
  40. Redlich K., Gortz B., Hayer S. et al. Overexpression of tumor necrosing factor causes bilateral sacroiliitis. Arthr. and Rheum. 2004; 50: 1001-1005.
  41. Tracey D., Klareskog L., Sasso E. H. et al. Tumor necrosis factor antagonist mechanisms of action: a comprehensive review. Pharmacol. Ther. 2008; 117: 244-279.
  42. Gorga J. C., Madden D. R., Prendergast J. K. et al. Crystallization and preliminary X-ray diffraction studies of the human major histocompatibility antigen HLA-B27. Proteins 1992; 12: 87-90.
  43. Madden D. R., Gorga J. C., Strominger J. L., Wiley D. C. The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 1992; 70: 1035-1048.
  44. Van Kaer L. Major histocompatibility complex class i-restricted antigen processing and presentation. Tissue Antigens 2002; 60: 1-9.
  45. Zhao L., Fong Y., Granfors K. et al. Identification of cytokines that might enhance the promoter activity of HLA-B27. J. Rheumatol. 2008; 35: 862-886.
  46. Kanaseki T., Blanchard N., Hammer G. E. et al. eRAAP synergizes with MHC class i molecules to make the final cut in the antigenic peptide precursors in the endoplasmic reticulum. Immunity 2006; 25: 795-806.
  47. Yan J. et al. In vivo role of eR-associated peptidase activity in tailoring peptides for presentation by MHC class ia and class ib molecules. J. Exp. Med. 2006; 203: 647-659.
  48. Turner M. J., Delay M. L., Bai S. et al. HLA-B27 up-regulation causes accumulation of misfolded heavy chains and correlates with the magnitude of the unfolded protein response in transgenic rats: implications for the pathogenesis of spondylarthritis-like disease. Arthr. and Rheum. 2007; 56: 215-223.
  49. Colbert R. A., Delay M. L., Layh-Schmitt G., Sowders D. P. HLA-B27 misfolding and spondyloarthropathies. Prion 2009; 3: 15-26.
  50. Smith J. A. et al. Endoplasmic reticulum stress and the unfolded protein response are linked to synergistic iFN-beta induction via X-box binding protein 1. Eur. J. Immunol. 2008; 38: 1194-1203.
  51. Dong W. et al. Upregulation of 78-kDa glucoseregulated protein in macrophages in peripheral joints of active ankylosing spondylitis. Scand. J. Rheumatol. 2008; 37: 427-434.
  52. Gu J. et al. Clues to pathogenesis of spondyloarthropathy derived from synovial fluid mononuclear cell gene expression profiles. J. Rheumatol. 2002; 29: 2159-2164.
  53. Young A. C., Zhang W., Sacchettini J. C., Nathenson S. G. MHC class i - peptide interactions and TCR recognition. Cancer Surv. 1995; 22: 17-36.
  54. López de Castro J. A. HLA-B27 and the pathogenesis of spondyloarthropathies. Immunol. Lett. 2007; 108: 27-33.
  55. Atagunduz P. et al. HLA-B27-restricted CD8+ T cell response to cartilage-derived self peptides in ankylosing spondylitis. Arthr. and Rheum. 2005; 52: 892-901.
  56. Fiorillo M. T., Maragno M., Butler R. et al. CD8(+) T-cell autoreactivity to an HLA-B27-restricted selfepitope correlates with ankylosing spondylitis. J. Clin. Invest. 2000; 106: 47-53.
  57. Zou J., Appel H., Rudwaleit M. et al. Analysls of the CD8+ T cell response to the G1 domain of aggrecan in ankylosing spondylitis. Ann. Rheum. Dis. 2005; 64: 722-729.
  58. Kollnberger S., Bowness P. The role of B27 heavy chain dimer immune receptor interactions in spondyloarthritis. Adv. Exp. Med. Biol. 2009; 649: 277-285.
  59. Kollnberger S. et al. Cell-surface expression and immune receptor recognition of HLA-B27 homodimers. Arthr. and Rheum. 2002; 46: 2972-2982.
  60. Kollnberger S. et al. HLA-B27 heavy chain homodimers are expressed in HLA-B27 transgenic rodent models of spondyloarthritis and are ligands for paired ig-like receptors. J. Immunol. 2004; 173: 1699-1710.
  61. Kollnberger S. et al. Interaction of HLA-B27 homodimers with KiR3DL1 and KiR3DL2, unlike HLA-B27 heterotrimers, is independent of the sequence of bound peptide. Eur. J. Immunol. 2007; 37: 1313-1322.
  62. Chan A. T., Kollnberger S. D., Wedderburn L. R., Bowness P. Expansion and enhanced survival of natural killer cells expressing the killer immunoglobulin-like receptor KiR3DL2 in spondylarthritis. Arthr. and Rheum. 2005; 52: 3586-3595.
  63. Ben Dror L., Barnea E., Beer I. et al. The HLA-B*2705 peptidome. Arthr. and Rheum. 2010; 62: 420-429.
  64. López de Castro J. A. The HLA-B27 peptidome: building on the cornerstone. Arthr. and Rheum. 2010; 62: 316-319.
  65. Hülsmeyer M. et al. Dual, HLA-B27 subtypedependent conformation of a self-peptide. J. Exp. Med. 2004; 199: 27l-281.
  66. Baeten D., Kruithof E., Breban M., Tak P. P. Spondylarthritis in the absence of B lymphocytes. Arthr. and Rheum. 2008; 58: 730-733.
  67. Nocturne G. et al. Rituximab in the spondyloarthropathies: data of eight patients followed up in the French Autoimmunity and Rituximab (AiR) registry. Ann. Rheum. Dis. 2010; 69: 471- 472.
  68. Milia A. F. et al. Evidence for the prevention of enthesitis in HLA-B27/hbeta2m transgenic rats treated with a monoclonal antibody against TNFalpha J. Cell. Mol. Med. doi:10.1111/ j.1582-49342009.00984.x.
  69. May E. et al. CD8 alpha beta T cells are not essential to the pathogenesis of arthritis or colitis in HLA-B27 transgenic rats. J. Immunol. 2003; 170: 1099-1105.
  70. Taurog J. D. et al. Spondylarthritis in HLA-B27/human beta2-microglobulin-transgenic rats is not prevented by lack of CD8. Arthr. and Rheum. 2009; 60: 1977-1984.
  71. Dhaenens M. et al. Dendritic cells from spondylarthritis-prone HLA-B27-transgenic rats display altered cytoskeletal dynamics, class ii major histocompatibility complex expression, and viability. Arthr. and Rheum. 2009; 60: 2622-2632.
  72. Fert I. et al. Correlation between dendritic cell functional defect and spondylarthritis phenotypes in HLA-B2/HUMAN beta2-microglobulin-transgenic rat lines. Arthr. and Rheum. 2008; 58: 3425-3429.
  73. Armaka M. et al. Mesenchymal cell targeting by TNF as a common pathogenic principle in chronic inflammatory joint and intestinal diseases. J. Exp. Med. 2008; 205: 331-337.
  74. Benjamin M., McGonagle D. Basic concepts of enthesis biology and immunology. J. Rheumatol. Suppl. 2009; 83: 12-13.
  75. Benjamin M. et al. Microdamage and altered vascularity at the enthesis-bone interface provides an anatomic explanation for bone involvement in the HLA-B27-associated spondylarthritides and allied disorders. Arthr. and Rheum. 2007; 56: 224-233.
  76. Mathieu A. et al. The interplay between the geographic distribution of HLA-B27 alleles and their role in infectious and autoimmune diseases: a unifying hypothesis. Autoimmun. Rev. 2009; 8: 420-425.
  77. Rashid T., Ebringer A. Ankylosing spondylitis is linked to Klebsiella - the evidence. Clin. Rheumatol. 2007; 26: 858-864.
  78. Hannu T., Inman R., Granfors K., Leirisalo-Repo M. Reactive arthritis or post-infectious arthritis? Best Pract. Res. Clin. Rheumatol. 2006; 20: 419-433.
  79. Appel H. et al. Use of HLA-B27 tetramers to identify to identify low-frequency antigen-specific T cells in Chlamydia-triggered reactive arthritis. Arthr. Res. Ther. 2004; 6: 521-534.
  80. Braun J. et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthr. and Rheum. 1995; 38: 499-505.
  81. Smolen J. S. et al. Radiographic changes in rheumatoid arthritis patients attaining different disease activity states with methotrexate monotherapy and infliximab plus methotrexate: the impacts of remission and tumour necrosis factor blockade. Ann. Rheum. Dis. 2009; 68: 823-827.
  82. Lories R. J., Derese I., de Bari C., Luyten F. P. Evidence for uncoupling of inflammation and joint remodeling in a mouse model of spondylarthritis. Arthr. and Rheum. 2007; 56: 489- 497.
  83. Maksymowych W. P. Disease modification in ankylosing spondylitis. Nat. Rev. Rheumatol. 2010; 6: 75-81.
  84. Neidhart M. et al. Expression of cathepsin K and matrix metalloprooteinase 1 indicate persistent osteodestructive activity in longstanding ankylosing spondylitis. Ann. Rheum. Dis. 2009; 68: 1334-1339.
  85. Walsh N. C., Gravallese E. M. Bone remodeling in rheumatic disease: a question of balance. Immunol. Rev. 2010; 233: 301-312.
  86. Lories R. J., Luyten F. P., de Vlam K. Progress in spondylarthritis. Mechanisms of new bone formation in spondylarthritis. Arthr. Res. Ther. 2009; 11: 221.
  87. Lories R. J., Luyten F. P. Bone morphogenetic protein signaling in joint homeostasis and disease. Cytokine Growth Factor Rev. 2005; 16: 287-298.
  88. Winkler D. G. et al. Noggin and sclerostin bone morphogenetic protein antagonists form a mutually inhibitory complex. J. Biol. Chem. 2004; 279: 36293-36298.
  89. van Bezooijen R. L. et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J. Exp. Med. 2004; 199: 805-814.
  90. Schett G., Zwerina J., David J. P. The role of Wnt proteins in arthritis. Nat. Clin. Pract. Rheumatol. 2008; 4: 473-480.
  91. Diarra D., Stolina M., Polzer K. et al. Dickkopf-1 is a master regulator of joint remodeling. Nat. Med. 2007; l3: 156-163.
  92. Underhardt S., Diarra D., Katzenbeisser J. et al. Blockade of Dickkopf (DKK)-1 induces fusion of sacroiliac joints. Ann. Rheum. Dis. 2010; 69: 592-597.
  93. Lories R. J., Derese I., Luyten F. P. Modulation of bone morphogenetic protein signaling inhibits the onset and progression of ankylosing enthesitis. J. Clin. Invest. 2005; 115: 1571-1579.
  94. Appel H. et al. Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthr. and Rheum. 2009; 60: 3257-3262.
  95. Daoussis D. et al. Evidence that Dkk-1 is dysfunctional in ankylosing spondylitis. Arthr. and Rheum. 2010; 62: 150-158.

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