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Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease

  • Spondyloarthritis (M Khan, Section Editor)
  • Published:
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Abstract

Purpose of Review

We review our current knowledge about the clinical features of patients with ankylosing spondylitis (AS) who possess HLA-B*27 versus those who lack this gene.

Recent Findings

ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. A genetic study supports the existence of an HLA-B27-independent common link between gut inflammation and AS. It is unusual to observe familial occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, psoriasis, or IBD.

Summary

Although there are many similarities among AS patients possessing HLA-B*27 versus those lacking this gene, the former group has a younger age of onset, a shorter delay in diagnosis, a better clinical response to tumor necrosis factor inhibitors, a greater familial occurrence, a greater risk for occurrence of acute anterior uveitis, and a lower risk for occurrence of psoriasis and IBD. ERAP1 association is present only in HLA-B*27+ patients, but other genetic associations are similar between the two groups. It is unusual to observe occurrence of primary AS among families of northern European extraction that show no segregation of HLA-B*27, IBD, or psoriasis. A recent genetic study supports the existence of an HLA-B*27-independent common link between gut inflammation and AS.

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References

  1. Akkoc N, Khan MA. Epidemiology of ankylosing spondylitis and related spondyloarthropathies. In: Weisman MH, Reveille JD, van der Heijde D, editors. Ankylosing spondylitis and the spondyloarthropathies. St. Louis: Mosby; 2006. p. 117–31.

    Google Scholar 

  2. Haroon NN, Paterson JM, Li P, Haroon N. Increasing proportion of female patients with ankylosing spondylitis: a population-based study of trends in the incidence and prevalence of AS. BMJ Open. 2014;4(12):e006634. doi:10.1136/bmjopen-2014-006634.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Caffrey MF, James DC. Human lymphocyte antigen association in ankylosing spondylitis. Nature. 1973;242(5393):121.

    Article  CAS  PubMed  Google Scholar 

  4. Schlosstein L, Terasaki PI, Bluestone R, Pearson CM. High association of an HL-A antigen, W27, with ankylosing spondylitis. N Engl J Med. 1973;288(14):704–6. doi:10.1056/NEJM197304052881403.

    Article  CAS  PubMed  Google Scholar 

  5. Brewerton DA, Hart FD, Nicholls A, Caffrey M, James DC, Sturrock RD. Ankylosing spondylitis and HL-A 27. Lancet. 1973;1(7809):904–7.

    Article  CAS  PubMed  Google Scholar 

  6. Brewerton DA. Discovery: HLA and disease. Curr Opin Rheumatol. 2003;15(4):369–73.

    Article  PubMed  Google Scholar 

  7. Khan MA. An update on the genetic polymorphism of HLA-B27 (HLA-B*27), comprising 204 alleles and 155 subtypes (and still counting). Curr Rheumatol Rep. 2017;In Press.

  8. •• Khan MA. Ankylosing spondylitis—axial Spondyloarthritis West Islip. New York: PCI (Professional Communications, Inc); 2016. Excellent handbook providing comprehensive yet concise up-to- date information on all aspects of axial spondyloarthritis, with particular emphasis on current treatment options including the latest biologic therapies.

  9. •• Bowness P. HLA-B27. Annu Rev Immunol. 2015;33:29–48. doi:10.1146/annurev-immunol-032414-112110. A thorough and comprehensive review discussing the function of HLA-B27, its disease associations, and its pathogenic role in AS.

    Article  CAS  PubMed  Google Scholar 

  10. •• Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, et al. Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nat Genet. 2016;48(5):510–8. doi:10.1038/ng.3528. This global study investigating the pleiotropy and the relationship between five common, inflammatory diseases that commonly occur together in families and in individuals showed that these conditions similar genetic backgrounds.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SG. The IPD and IMGT/HLA database: allele variant databases. Nucleic Acids Res. 2015;43(Database issue):D423–31. doi:10.1093/nar/gku1161.

    Article  PubMed  Google Scholar 

  12. Braun J, Sieper J. Ankylosing spondylitis. Lancet. 2007;369(9570):1379–90. doi:10.1016/s0140-6736(07)60635-7.

    Article  PubMed  Google Scholar 

  13. Rudwaleit M, Khan MA, Sieper J. The challenge of diagnosis and classification in early ankylosing spondylitis: do we need new criteria? Arthritis Rheum. 2005;52(4):1000–8. doi:10.1002/art.20990.

    Article  PubMed  Google Scholar 

  14. Sherlock JP, Joyce-Shaikh B, Turner SP, Chao CC, Sathe M, Grein J, et al. IL-23 induces spondyloarthropathy by acting on ROR-gammat+ CD3+CD4-CD8- entheseal resident T cells. Nat Med. 2012;18(7):1069–76. doi:10.1038/nm.2817.

    Article  CAS  PubMed  Google Scholar 

  15. Lin P, Bach M, Asquith M, Lee AY, Akileswaran L, Stauffer P, et al. HLA-B27 and human beta2-microglobulin affect the gut microbiota of transgenic rats. PLoS One. 2014;9(8):e105684. doi:10.1371/journal.pone.0105684.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Khan MA, Mathieu A, Sorrentino R, Akkoc N. The pathogenetic role of HLA-B27 and its subtypes. Autoimmun Rev. 2007;6(3):183–9. doi:10.1016/j.autrev.2006.11.003.

    Article  CAS  PubMed  Google Scholar 

  17. • Brown MA, Kenna T, Wordsworth BP. Genetics of ankylosing spondylitis - insights into pathogenesis. Nat Rev Rheumatol. 2015;advance online publication. doi:10.1038/nrrheum.2015.133. This paper provides a comprehensive review of the recent progress in AS genetics and describes how the recently discovered genetic associations has expanded our understanding of its pathogenesis and led to the development of novel therapeutic strategies.

  18. Evans DM, Spencer CCA, Pointon JJ, Su Z, Harvey D, Kochan G, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet. 2011;43(8):761–7. http://www.nature.com/ng/journal/v43/n8/abs/ng.873.html - supplementary-information

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Haroon N, Tsui FW, Uchanska-Ziegler B, Ziegler A, Inman RD. Endoplasmic reticulum aminopeptidase 1 (ERAP1) exhibits functionally significant interaction with HLA-B27 and relates to subtype specificity in ankylosing spondylitis. Ann Rheum Dis. 2012;71(4):589–95. doi:10.1136/annrheumdis-2011-200347.

    Article  CAS  PubMed  Google Scholar 

  20. International Genetics of Ankylosing Spondylitis C, Cortes A, Hadler J, Pointon JP, Robinson PC, Karaderi T, et al. Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nat Genet. 2013;45(7):730–8. doi:10.1038/ng.2667.

    Article  Google Scholar 

  21. Keidel S, Chen L, Pointon J, Wordsworth P. ERAP1 and ankylosing spondylitis. Curr Opin Immunol. 2013;25(1):97–102.

    Article  CAS  PubMed  Google Scholar 

  22. Reeves E, Colebatch-Bourn A, Elliott T, Edwards CJ, James E. Functionally distinct ERAP1 allotype combinations distinguish individuals with ankylosing spondylitis. Proc Natl Acad Sci. 2014;111(49):17594–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Khan MA, Magrey M. Gene–gene interactions of HLA-B27 and ERAP1 in ankylosing spondylitis: finding the pieces of the puzzle. Int J Clin. 2014;9(6):539–42.

    CAS  Google Scholar 

  24. Hersh AH, Stecher RM, Solomon WM, Wolpaw R, Hauser H. Heredity in ankylosing spondylitis; a study of fifty families. Am J Hum Genet. 1950;2(4):391–408.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. van der Linden S, Valkenburg H, Cats A. The risk of developing ankylosing spondylitis in HLA-B27 positive individuals: a family and population study. Br J Rheumatol. 1983;22(4 Suppl 2):18–9.

    Article  PubMed  Google Scholar 

  26. Brown MA, Kennedy LG, MacGregor AJ, Darke C, Duncan E, Shatford JL, et al. Susceptibility to ankylosing spondylitis in twins: the role of genes, HLA, and the environment. Arthritis Rheum. 1997;40(10):1823–8. doi:10.1002/1529-0131(199710)40:10<1823::AID-ART15>3.0.CO;2–1.

    Article  CAS  PubMed  Google Scholar 

  27. Brown MA, Laval SH, Brophy S, Calin A. Recurrence risk modelling of the genetic susceptibility to ankylosing spondylitis. Ann Rheum Dis. 2000;59(11):883–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Woodrow JC, Eastmond CJ. HLA B27 and the genetics of ankylosing spondylitis. Ann Rheum Dis. 1978;37(6):504–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hochberg MC, Bias WB, Arnett Jr FC. Family studies in HLA-B27 associated arthritis. Medicine (Baltimore). 1978;57(5):463–75.

    Article  CAS  Google Scholar 

  30. • Yang M, Xu M, Pan X, Hu Z, Li Q, Wei Y, et al. Epidemiological comparison of clinical manifestations according to HLA-B*27 carrier status of Chinese ankylosing spondylitis patients. Tissue Antigens. 2013;82(5):338–43. doi:10.1111/tan.12186. This nationwide epidemiological study from China investigated and reported on the clinical diversity between HLA-B27+ and HLA-B27− AS patients.

    Article  CAS  PubMed  Google Scholar 

  31. Chung HY, Machado P, van der Heijde D, D’Agostino MA, Dougados M. HLA-B27 positive patients differ from HLA-B27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis. Ann Rheum Dis. 2011;70(11):1930–6. doi:10.1136/ard.2011.152975.

    Article  PubMed  Google Scholar 

  32. Sampaio-Barros PD, Bertolo MB, Kraemer MH, Neto JF, Samara AM. Primary ankylosing spondylitis: patterns of disease in a Brazilian population of 147 patients. J Rheumatol. 2001;28(3):560–5.

    CAS  PubMed  Google Scholar 

  33. Nazarinia MA, Ghaffarpasand F, Heiran HR, Habibagahi Z. Pattern of ankylosing spondylitis in an Iranian population of 98 patients. Mod Rheumatol. 2009;19(3):309–15. doi:10.1007/s10165-009-0153-5.

    Article  PubMed  Google Scholar 

  34. Paardt M, Dijkmans B, Giltay E, van der Horst-Bruinsma I. Dutch patients with familial and sporadic ankylosing spondylitis do not differ in disease phenotype. J Rheumatol. 2002;29(12):2583–4.

    PubMed  Google Scholar 

  35. Kim HW, Choe HR, Lee SB, Chang WI, Chae HJ, Moon JY, et al. Phenotype difference between familial and sporadic ankylosing spondylitis in Korean patients. J Korean Med Sci. 2014;29(6):782–7. doi:10.3346/jkms.2014.29.6.782.

    Article  PubMed  PubMed Central  Google Scholar 

  36. de Vlam K, Vastesaeger N, Brasseur J, Boonen A, Lenaerts J, Lesaffre E, et al. Belgian patients with familial and sporadic ankylosing spondylitis differ in disease phenotype. Arthritis Rheum. 2006;54:S717–8.

    Google Scholar 

  37. Calin A, Kennedy LG, Edmunds L, Will R. Familial versus sporadic ankylosing spondylitis. Two different diseases? Arthritis Rheum. 1993;36(5):676–81.

    Article  CAS  PubMed  Google Scholar 

  38. Almodovar R, Font P, Zarco-Montejo P, Collantes E, Mulero J, Gratacos J, et al. Phenotypic differences between familial versus sporadic ankylosing spondylitis: a cross-sectional Spanish registry of spondyloarthropathies (REGISPONSER). Clin Exp Rheumatol. 2011;29(5):822–7.

    PubMed  Google Scholar 

  39. Chou CT, Lin KC, Wei JC, Tsai WC, Ho HH, Hwang CM, et al. Study of undifferentiated spondyloarthropathy among first-degree relatives of ankylosing spondylitis probands. Rheumatology (Oxford). 2005;44(5):662–5. doi:10.1093/rheumatology/keh577.

    Article  CAS  Google Scholar 

  40. Joshi R, Reveille JD, Brown MA, Weisman MH, Ward MM, Gensler LS, et al. Is there a higher genetic load of susceptibility loci in familial ankylosing spondylitis? Arthritis Care Res (Hoboken). 2012;64(5):780–4. doi:10.1002/acr.21601.

    Article  CAS  Google Scholar 

  41. Khan MA, Kushner I, Braun WE, Zachary AA, Steinberg AG. HLA--B27 homozygosity in ankylosing spondylitis: relationship to risk and severity. Tissue Antigens. 1978;11(5):434–8.

    Article  CAS  PubMed  Google Scholar 

  42. Jaakkola E, Herzberg I, Laiho K, Barnardo MC, Pointon JJ, Kauppi M, et al. Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis. Ann Rheum Dis. 2006;65(6):775–80. doi:10.1136/ard.2005.041103.

    Article  CAS  PubMed  Google Scholar 

  43. Kim TJ, Na KS, Lee HJ, Lee B, Kim TH. HLA-B27 homozygosity has no influence on clinical manifestations and functional disability in ankylosing spondylitis. Clin Exp Rheumatol. 2009;27(4):574–9.

  44. Suarez-Almazor ME, Russell AS. B27 homozygosity and ankylosing spondylitis. J Rheumatol. 1987;14(2):302–4.

    CAS  PubMed  Google Scholar 

  45. Arnett Jr FC, Schacter BZ, Hochberg MC, Hsu SH, Bias WB. Homozygosity for HLA-B27. Impact on rheumatic disease expression in two families. Arthritis Rheum. 1977;20(3):797–804.

    Article  PubMed  Google Scholar 

  46. •• Kim T-J, Sung I-H, Lee S, Joo KB, Choi JH, Park D-J, et al. HLA-B27 homozygosity has no influence on radiographic damage in ankylosing spondylitis: Observation Study of Korean spondyloArthropathy Registry (OSKAR) data. Joint Bone Spine. 2013;80(5):488–91. doi:10.1016/j.jbspin.2012.12.003. This study, with the largest number of HLA-B*27 homozygous cases with AS, found no role for HLA-B*27 homozygosity on the structural progression in this disease.

  47. Linssen A. B27+ disease versus B27- disease. Scand J Rheumatol Suppl. 1990;87:111–8. discussion 8–9

    Article  CAS  PubMed  Google Scholar 

  48. Kim TJ, Kim TH. Clinical spectrum of ankylosing spondylitis in Korea. Joint Bone Spine. 2010;77(3):235–40. doi:10.1016/j.jbspin.2009.11.015.

    Article  PubMed  Google Scholar 

  49. Olivieri I, D’Angelo S, Padula A, Leccese P, Palazzi C. Spondyloarthritis with onset after age 45. Curr Rheumatol Rep. 2013;15(12):374. doi:10.1007/s11926-013-0374-7.

    Article  PubMed  Google Scholar 

  50. Van der Linden JM, De Ceulaer K, Van Romunde LK, Cats A. Ankylosing spondylitis without HLA B27. J Rheumatol Suppl. 1977;3:54–6.

    CAS  PubMed  Google Scholar 

  51. Khan MA, Kushner I, Braun WE. Comparison of clinical features in HLA-B27 positive and negative patients with ankylosing spondylitis. Arthritis Rheum. 1977;20(4):909–12.

    Article  CAS  PubMed  Google Scholar 

  52. Feldtkeller E, Khan MA, van der Heijde D, van der Linden S, Braun J. Age at disease onset and diagnosis delay in HLA-B27 negative vs. positive patients with ankylosing spondylitis. Rheumatol Int. 2003;23(2):61–6. doi:10.1007/s00296-002-0237-4.

    PubMed  Google Scholar 

  53. Rudwaleit M, Haibel H, Baraliakos X, Listing J, Marker-Hermann E, Zeidler H, et al. The early disease stage in axial spondylarthritis: results from the German Spondyloarthritis Inception Cohort. Arthritis Rheum. 2009;60(3):717–27. doi:10.1002/art.24483.

    Article  CAS  PubMed  Google Scholar 

  54. Dougados M, d’Agostino MA, Benessiano J, Berenbaum F, Breban M, Claudepierre P, et al. The DESIR cohort: a 10-year follow-up of early inflammatory back pain in France: study design and baseline characteristics of the 708 recruited patients. Joint, bone, spine : revue du rhumatisme. 2011;78(6):598–603. doi:10.1016/j.jbspin.2011.01.013.

    Article  Google Scholar 

  55. Lee JH, Jun JB, Jung S, Bae SC, Yoo DH, Kim TY, et al. Higher prevalence of peripheral arthritis among ankylosing spondylitis patients. J Korean Med Sci. 2002;17(5):669–73.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Amor B, Santos RS, Nahal R, Listrat V, Dougados M. Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol. 1994;21(10):1883–7.

    CAS  PubMed  Google Scholar 

  57. Stolwijk C, van Tubergen A, Castillo-Ortiz JD, Boonen A. Prevalence of extra-articular manifestations in patients with ankylosing spondylitis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74(1):65–73. doi:10.1136/annrheumdis-2013-203582.

    Article  PubMed  Google Scholar 

  58. Wakefield D, Chang JH, Amjadi S, Maconochie Z, Abu El-Asrar A, McCluskey P. What is new HLA-B27 acute anterior uveitis? Ocul Immunol Inflamm. 2011;19(2):139–44. doi:10.3109/09273948.2010.542269.

    Article  CAS  PubMed  Google Scholar 

  59. Nahir M, Scharf Y, Brik R, Scharf Y, Gidoni O, Barzilai A. The influence of HL-A B27 on the clinical picture of ankylosing spondylitis. Rheumatol Rehabil. 1979;18(1):10–2.

  60. Queiro R, Morante I, Cabezas I, Acasuso B. HLA-B27 and psoriatic disease: a modern view of an old relationship. Rheumatology (Oxford). 2016;55(2):221–9. doi:10.1093/rheumatology/kev296.

    Article  Google Scholar 

  61. Queiro R, Sarasqueta C, Belzunegui J, Gonzalez C, Figueroa M, Torre-Alonso JC. Psoriatic spondyloarthropathy: a comparative study between HLA-B27 positive and HLA-B27 negative disease. Semin Arthritis Rheum. 2002;31(6):413–8.

    Article  PubMed  Google Scholar 

  62. Armstrong RD, Panayi GS, Welsh KI. Histocompatibility antigens in psoriasis, psoriatic arthropathy, and ankylosing spondylitis. Ann Rheum Dis. 1983;42(2):142–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Machado P, Landewe R, Braun J, Baraliakos X, Hermann KG, Hsu B, et al. Ankylosing spondylitis patients with and without psoriasis do not differ in disease phenotype. Ann Rheum Dis. 2013;72(6):1104–7. doi:10.1136/annrheumdis-2012-202922.

    Article  PubMed  Google Scholar 

  64. Braun J, Rudwaleit M, Kary S, Kron M, Wong RL, Kupper H. Clinical manifestations and responsiveness to adalimumab are similar in patients with ankylosing spondylitis with and without concomitant psoriasis. Rheumatology (Oxford). 2010;49(8):1578–89. doi:10.1093/rheumatology/keq129.

    Article  CAS  Google Scholar 

  65. Sinikumpu SP, Huilaja L, Jokelainen J, Koiranen M, Auvinen J, Hagg PM, et al. High prevalence of skin diseases and need for treatment in a middle-aged population. A Northern Finland Birth Cohort 1966 study. PLoS One. 2014;9(6):e99533. doi:10.1371/journal.pone.0099533.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Rudwaleit M, Baeten D. Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol. 2006;20(3):451–71. doi:10.1016/j.berh.2006.03.010.

    Article  PubMed  Google Scholar 

  67. Voulgari PV. Rheumatological manifestations in inflammatory bowel disease. Ann Gastroenterol. 2011;24(3):173–80.

    PubMed  PubMed Central  Google Scholar 

  68. Mielants H, Veys EM, Cuvelier C, De Vos M. Subclinical involvement of the gut in undifferentiated spondylarthropathies. Clin Exp Rheumatol. 1989;7(5):499–504.

    CAS  PubMed  Google Scholar 

  69. Palm O, Moum B, Ongre A, Gran JT. Prevalence of ankylosing spondylitis and other spondyloarthropathies among patients with inflammatory bowel disease: a population study (the IBSEN study). J Rheumatol. 2002;29(3):511–5.

    PubMed  Google Scholar 

  70. Hamersma J, Cardon LR, Bradbury L, Brophy S, van der Horst-Bruinsma I, Calin A, et al. Is disease severity in ankylosing spondylitis genetically determined? Arthritis Rheum. 2001;44(6):1396–400. doi:10.1002/1529-0131(200106)44:6<1396::AID-ART233>3.0.CO;2-A.

    Article  CAS  PubMed  Google Scholar 

  71. Brophy S, Hickey S, Menon A, Taylor G, Bradbury L, Hamersma J, et al. Concordance of disease severity among family members with ankylosing spondylitis? J Rheumatol. 2004;31(9):1775–8.

    PubMed  Google Scholar 

  72. Brown MA, Kennedy LG, Darke C, Gibson K, Pile KD, Shatford JL, et al. The effect of HLA-DR genes on susceptibility to and severity of ankylosing spondylitis. Arthritis Rheum. 1998;41(3):460–5. doi:10.1002/1529-0131(199803)41:3<460::AID-ART12>3.0.CO;2-X.

    Article  CAS  PubMed  Google Scholar 

  73. Cortes A, Maksymowych WP, Wordsworth BP, Inman RD, Danoy P, Rahman P, et al. Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis. Ann Rheum Dis. 2015;74(7):1387–93. doi:10.1136/annrheumdis-2013-204835.

    Article  CAS  PubMed  Google Scholar 

  74. Boonen A, vander Cruyssen B, de Vlam K, Steinfeld S, Ribbens C, Lenaerts J, et al. Spinal radiographic changes in ankylosing spondylitis: association with clinical characteristics and functional outcome. J Rheumatol. 2009;36(6):1249–55. doi:10.3899/jrheum.080831.

    Article  PubMed  Google Scholar 

  75. Ward MM, Hendrey MR, Malley JD, Learch TJ, Davis Jr JC, Reveille JD, et al. Clinical and immunogenetic prognostic factors for radiographic severity in ankylosing spondylitis. Arthritis Rheum. 2009;61(7):859–66. doi:10.1002/art.24585.

  76. Atagunduz P, Aydin SZ, Bahadir C, Erer B, Direskeneli H. Determinants of early radiographic progression in ankylosing spondylitis. J Rheumatol. 2010;37(11):2356–61. doi:10.3899/jrheum.100094.

    Article  PubMed  Google Scholar 

  77. •• Ramiro S, Stolwijk C, van Tubergen A, van der Heijde D, Dougados M, van den Bosch F, et al. Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study. Ann Rheum Dis. 2013; doi:10.1136/annrheumdis-2013-204055. This long term prospective data from the European Outcome in Ankylosing Spondylitis International Study (OASIS) radiographic progression in AS is highly variable in the individual patient, more severe in HLA-B*27-positive male patients and those with a higher existing level of spinal damage present at baseline.

  78. Poddubnyy D, Haibel H, Listing J, Marker-Hermann E, Zeidler H, Braun J, et al. Baseline radiographic damage, elevated acute-phase reactant levels, and cigarette smoking status predict spinal radiographic progression in early axial spondyloarthritis. Arthritis Rheum. 2012;64(5):1388–98. doi:10.1002/art.33465.

    Article  PubMed  Google Scholar 

  79. Poddubnyy D, Rudwaleit M, Haibel H, Listing J, Marker-Hermann E, Zeidler H, et al. Rates and predictors of radiographic sacroiliitis progression over 2 years in patients with axial spondyloarthritis. Ann Rheum Dis. 2011;70(8):1369–74. doi:10.1136/ard.2010.145995.

    Article  PubMed  Google Scholar 

  80. Bennett AN, McGonagle D, O’Connor P, Hensor EM, Sivera F, Coates LC, et al. Severity of baseline magnetic resonance imaging-evident sacroiliitis and HLA-B27 status in early inflammatory back pain predict radiographically evident ankylosing spondylitis at eight years. Arthritis Rheum. 2008;58(11):3413–8. doi:10.1002/art.24024.

    Article  CAS  PubMed  Google Scholar 

  81. van der Heijde D, Kivitz A, Schiff MH, Sieper J, Dijkmans BA, Braun J, et al. Efficacy and safety of adalimumab in patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2006;54(7):2136–46. doi:10.1002/art.21913.

    Article  PubMed  Google Scholar 

  82. Rudwaleit M, Listing J, Brandt J, Braun J, Sieper J. Prediction of a major clinical response (BASDAI 50) to tumour necrosis factor alpha blockers in ankylosing spondylitis. Ann Rheum Dis. 2004;63(6):665–70. doi:10.1136/ard.2003.016386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Vastesaeger N, van der Heijde D, Inman RD, Wang Y, Deodhar A, Hsu B, et al. Predicting the outcome of ankylosing spondylitis therapy. Ann Rheum Dis. 2011;70(6):973–81. doi:10.1136/ard.2010.147744.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Baraliakos X, Koenig AS, Jones H, Szumski A, Collier D, Bananis E. Predictors of clinical remission under anti-tumor necrosis factor treatment in patients with ankylosing spondylitis: pooled analysis from large randomized clinical trials. J Rheumatol. 2015;42(8):1418–26.

    Article  CAS  PubMed  Google Scholar 

  85. Rudwaleit M, Claudepierre P, Wordsworth P, Cortina EL, Sieper J, Kron M, et al. Effectiveness, safety, and predictors of good clinical response in 1250 patients treated with adalimumab for active ankylosing spondylitis. J Rheumatol. 2009;36(4):801–8. doi:10.3899/jrheum.081048.

    Article  CAS  PubMed  Google Scholar 

  86. Fagerli KM, Lie E, Heiberg MS, van der Heijde D, Kalstad S, Knut M, et al. Predictors of ASDAS major improvement in patients with ankylosing spondylitis (AS) receiving their first TNF inhibitor: results from a longitudinal observational study. Arthritis Rheum. 2011;63(Suppl 10):533.

    Google Scholar 

  87. Maneiro JR, Souto A, Salgado E, Mera A, Gomez-Reino JJ. Predictors of response to TNF antagonists in patients with ankylosing spondylitis and psoriatic arthritis: systematic review and meta-analysis. RMD Open. 2015;1(1):e000017. doi:10.1136/rmdopen-2014-000017.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Haibel H, Rudwaleit M, Listing J, Heldmann F, Wong RL, Kupper H, et al. Efficacy of adalimumab in the treatment of axial spondylarthritis without radiographically defined sacroiliitis: results of a twelve-week randomized, double-blind, placebo-controlled trial followed by an open-label extension up to week fifty-two. Arthritis Rheum. 2008;58(7):1981–91. doi:10.1002/art.23606.

    Article  CAS  PubMed  Google Scholar 

  89. Sieper J, van der Heijde D, Dougados M, Mease PJ, Maksymowych WP, Brown MA, et al. Efficacy and safety of adalimumab in patients with non-radiographic axial spondyloarthritis: results of a randomised placebo-controlled trial (ABILITY-1). Ann Rheum Dis. 2013;72(6):815–22. doi:10.1136/annrheumdis-2012-201766.

    Article  CAS  PubMed  Google Scholar 

  90. Dougados M, van der Heijde D, Sieper J, Braun J, Maksymowych WP, Citera G, et al. Symptomatic efficacy of etanercept and its effects on objective signs of inflammation in early nonradiographic axial spondyloarthritis: a multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014;66(8):2091–102. doi:10.1002/art.38721.

    Article  CAS  PubMed  Google Scholar 

  91. Sieper J, van der Heijde D, Dougados M, Maksymowych WP, Scott BB, Boice JA, et al. A randomized, double-blind, placebo-controlled, sixteen-week study of subcutaneous golimumab in patients with active nonradiographic axial spondyloarthritis. Arthritis Rheumatol. 2015;67(10):2702–12. doi:10.1002/art.39257.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Thjodleifsson B, Geirsson AJ, Bjornsson S, Bjarnason I. A common genetic background for inflammatory bowel disease and ankylosing spondylitis: a genealogic study in Iceland. Arthritis Rheum. 2007;56(8):2633–9. doi:10.1002/art.22812.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Izmir, Turkey

    Nurullah Akkoç

  2. Department of Rheumatology, Faculty of Medicine, Dokuz Eylul University, Balcova, 35340, Izmir, Turkey

    Handan Yarkan & Gökçe Kenar

  3. MetroHealth Medical Center, Case Western Reserve University, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA

    Muhammad A. Khan

Authors
  1. Nurullah Akkoç
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  2. Handan Yarkan
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  3. Gökçe Kenar
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  4. Muhammad A. Khan
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Correspondence to Nurullah Akkoç.

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Conflict of Interest

Gökçe Kenar and Handan Yarkan declare that they have no conflict of interest.

Nurullah Akkoc reports consulting and/or speaking fees and/or honoraria from Pfizer, AbbVie, MSD, and UCB.

Muhammad A Khan reports consulting and/or speaking fees from AbbVie and Novartis.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Spondyloarthritis

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Akkoç, N., Yarkan, H., Kenar, G. et al. Ankylosing Spondylitis: HLA-B*27-Positive Versus HLA-B*27-Negative Disease. Curr Rheumatol Rep 19, 26 (2017). https://doi.org/10.1007/s11926-017-0654-8

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