Establishing a Causal Link between Ankylosing Spondylitis and Inflammatory Bowel Disease: A Review of the Literature
Keywords:HLA-B27 Antigen, Spondylitis, Ankylosing, Inflammatory Bowel Diseases, Sacroiliitis, Killer Cells, Natural
The link between ankylosing spondylitis and inflammatory bowel disease is unclear, however it is hypothesized that there is a causal link between the inheritance of a human leukocyte antigen B27 allele and the development of inflammatory bowel disease symptoms in ankylosing spondylitis patients. Research articles assessing the relationship between ankylosing spondylitis, inflammatory bowel disease and the human leukocyte antigen B27 antigen were collected from the PubMed database. Patients expressing the human leukocyte antigen B27 allele have a demonstrated predisposition to developing symptoms of inflammatory bowel disease and sacroiliitis in ankylosing spondylitis. However, human leukocyte antigen B27 is considered to be just a contributing factor in the disease, as interleukin-23, natural killer cells, and alterations to the microbiome have also demonstrated an active role in the development of symptoms. More longitudinal studies using larger cohorts are needed to further substantiate a direct causal relationship between ankylosing spondylitis and inflammatory bowel disease.
2. Turkcapar N, Toruner M, Soykan I, Aydintug OT, Cetinkaya H, Duzgun N, et al. The prevalence of extraintestinal manifestations and HLA association in pa¬tients with inflammatory bowel disease. Rheumatol Int. 2006 May;26(7):663-8.
3. Tsui FW, Tsui HW, Akram A, Haroon N, Inman RD. The genetic basis of ankylosing spondylitis: new insights into disease pathogenesis. Appl Clin Ge¬net. 2014 May 22;7:105-15.
4. De Vos M. Joint involvement associated with inflammatory bowel disease. Dig Dis. 2009;27(4):511-5.
5. Rudwaleit M, Baeten D. Ankylosing spondylitis and bowel disease. Best Pract Res Clin Rheumatol. 2006 Jun;20(3):451-71.
6. Aydin SZ, Atagunduz P, Temel M, Bicakcigil M, Tasan D, Direskeneli H. An¬ti-Saccharomyces cerevisiae antibodies (ASCA) in spondyloarthropathies: a reassessment. Rheumatology (Oxford). 2008 Feb;47(2):142-4.
7. Orchard TR, Holt H, Bradbury L, Hammersma J, McNally E, Jewell DP, et al. The prevalence, clinical features and association of HLA-B27 in sacroilitis associated with established Crohn’s Disease. Aliment Pharmacol Ther. 2009 Jan;29(2):193-7.
8. Jacques P, Elewaut D. Joint expedition: linking gut inflammation to arthritis. Mucosal Immunol. 2008 Sep;1(5):364-71.
9. Steer S, Jones H, Hibbert J, Kondeatis E, Vaughan R, Sanderson J, et al. Low back pain, sacroiliitis, and the relationship with HLA-B27 in Crohn’s disease. J Rheumatol. 2003 Mar;30(3):518-22.
10. Cho JH. The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol. 2008 Jun;8(6):458-66.
11. 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 Oct;40(10):1823-8.
12. Jarvinen P. Occurrence of ankylosing spondylitis in a nationwide series of twins. Arthritis Rheum. 1995 Mar;38(3):381-3.
13. Ciccia F, Accardo-Palumbo A, Rizzo A, Guggino G, Raimondo S, Giardina A, et al. Evidence that autophagy, but not the unfolded protein response, regu¬lates the expression of IL-23 in the gut of patients with ankylosing spondylitis and subclinical gut inflammation. Ann Rheum Dis. 2014 Aug;73(8):1566-74.
14. Haroon N. Endoplasmic reticulum aminopeptidase 1 and interleukin-23 receptor in ankylosing spondylitis. Curr Rheumatol Rep. 2012 Oct;14(5):383-9.
15. Davis JC Jr. Understanding the role of tumour necrosis factor inhibition in ankylosing spondylitis. Semin Arthritis Rheum. 2005 Feb;34(4):668-77.
16. Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and TH17 cells. Annu Rev Immunol. 2009;27:485-517.
17. Smith JA, Colbert RA. Review: the interleukin-23/interleukin 17 axis in spondyloarthritis pathogenesis: TH17 and beyond. Arthritis Rheumatol. 2014 Feb;66(2):231-41.
18. Baeten D, Baraliakos X, Braun J, Sieper J, Emery P, van der Heijde D, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Nov;382(9906):1705-13.
19. Evans DM, Spencer CC, Pointon JJ, Su Z, Harvey D, Kochan G, et al. Interac¬tion between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nat Genet. 2011 Jul 10;43(8):761-7.
20. Tsai WC, Chen CJ, Yen JH, Ou TT, Tsai JJ, Liu CS, et al. Free HLA class I heavy chain-carrying monocytes—a potential role in the pathogenesis of spondyloar-thropathies. J Rheumatol. 2002 May;29(5):966-72.
21. Kollnberger S, Chan A, Sun MY, Chen LY, Wright C, di Gleria K, et al. Interac¬tion of HLA-B27 homodimers with KIR3DL1 and KIR3DL2, unlike HLA-B27 hete-rotrimers, is independent of the sequence of bound peptide. Eur J Immunol. 2007 May;37(5):1313-22.
22. Ebringer A, Rashid T, Tiwana H, Wilson C. A possible link between Crohn’s
disease and ankylosing spondylitis via Klebsiella infections. Clin Rheumatol. 2007 Mar;26(3):289-97.
23. Ebringer A, Rashid T, Wilson C, Ptaszynska,T, Fielder M. Ankylosing spond¬ylitis, HLA-B27 and Klebsiella – an overview: proposal for early diagnosis and treatment. Curr Rheumatol Rev. 2006;2(1):55-68.
24. Wilson C, Rashid T, Tiwana H, Beyan H, Hughes L, Bansal S, et al. Cyto¬toxicity responses to peptide antigens in rheumatoid arthritis and ankylosing spondylitis. J Rheumatol. 2003 May;30(5):972-8.
25. Faustini F, Zoli A, Ferraccioli GF. Immunologic and genetic links between spondyloarthropathies and inflammatory bowel diseases. Eur Rev Med Phar¬macol Sci. 2009 Mar;13 Suppl 1:1-9.
26. Martínez-González O, Cantero-Hinojosa J, Paule-Sastre P, Gómez-Magán JC, Salvatierra-Ríos D. Intestinal permeability in patients with ankylosing spond¬ylitis and their healthy relatives. Br J Rheumatol.1994 Jul;33(7):644-7.
27. Demetter P, Baeten D, De Keyse F, De Vos M, Van Damme N, Vebruggen G, et al. Subclinical gut inflammation in spondyloarthropathy patients is asso¬ciated with upregulation of the E-cadherin/catenin complex. Ann Rheum Dis. 2000 Mar;59(3):211-6.
28. De Rycke L, Vandooren B, Kuithof E, De Keyser F, Veys EM, Baeten D. Tu¬mour necosis factor alpha blockade treatment down-modulates the increased systemic and local expression of Toll-like receptor 2 and Toll-like receptor 4 in spondylarthropathy. Arthritis Rheum. 2005 Jul;52(7):2146-58.
29. Yang ZX, Liang Y, Zhu Y, Li C, Zhang LZ, Zeng XM, et al. Increased expres¬sion of Toll-like receptor 4 in peripheral blood leucocytes and serum levels of some cytokines in patients with ankylosing spondylitis. Clin Exp Immunol. 2007 Jul;149(1):48-55.
30. Cauli A, Piga M, Dessole G, Porru G, Floris A, Vacca A, et al. Killer-cell im¬munoglobulin-like receptors (KIR) and HLA-class I heavy chains in ankylosing spondylitis. Drug Dev Res. 2014 Nov;75 Suppl 1:S15-9.
31. Haroon N, Tsui FW, Uchanska-Ziegler B, Ziegler A, Inman RD. Endoplasmic reticulum aminopeptidase 1 (ERAP1) exhibits functionally significant interac¬tion with HLA-B27 and relates to subtype specificity in ankylosing spondylitis. Ann Rheum Dis. 2012 Apr;71(4):589-95.
32. Lopez-Larrea C, Blanco-Gelaz MA, Torre-Alonso JC, Bruges Armas J, Sua¬rez-Alvarez B, Pruneda L, et al. Contribution of KIR3DL1/3DS1 to ankylosing spondylitis in human leukocyte antigen-B27 Caucasian populations. Arthritis Res Ther. 2006;8(4):R101.
33. Matzkies FG, Targan SR, Berel D, Landers CJ, Reveille JD, McGovern DP, et al. Markers of intestinal inflammation in patients with ankylosing spondylitis: a pilot study. Arthritis Res Ther. 2012 Nov;14(6):R261.
34. Togrol RE, Nalbant S, Solmazgül E, Ozyurt M, Kaplan M, Kiralp MZ, et al. The significance of coeliac disease antibodies in patients with ankylosing spondylitis: a case-controlled study. J Int Med Res. 2009 Jan-Feb;37(1):220-6.
35. Skare TL, Bortoluzzo AB, Gonçalves CR, Braga da Silva JA, Ximenes AC, Bér¬tolo MB, et al. Ethnic influence in clinical and functional measures of Brazilian patients with spondyloarthritis. J Rheumatol. 2012 Jan;39(1):141-7.
36. Wei JC, Hsu YW, Hung KS, Wong RH, Huang CH, Liu YT, et al. Association study of polymorphisms rs4552569 and rs17095830 and the risk of ankylosing spondylitis in a Taiwanese population. PLoS One. 2013;8(1):e52801
37. Duarte AP, Marques CD, Bortoluzzo AB, Gonçalves CR, da Silva JA, Ximenes AC, et al. [Epidemiologic profile of juvenile-onset compared to adult-onset spondyloarthritis in a large Brazilian cohort]. Rev Bras Reumatol. 2014 Nov- Dec;54(6):424-30. Portuguese
38. D'Incà R, Podswiadek M, Ferronato A, Punzi L, Salvagnini M, Sturniolo GC. Articular manifestations in inflammatory bowel disease patients: a prospecti¬ve study. Dig Liver Dis. 2009 Aug;41(8):565-9.
39. Tsui FW, Tsui HW, Las Heras F, Pritzker KP, Inman RD. Serum levels of novel noggin and sclerostin-immune complexes are elevated in ankylosing spond¬ylitis. Ann Rheum Dis. 2014 Oct;73(10):1873-9.
40. Riente L, Chimenti D, Pratesi F, Delle Sedie A, Tommasi S, Tommasi C, et al. Antibodies to tissue transglutaminase and Saccharomyces cerevi¬
siae in ankylosing spondylitis and psoriatic arthritis. J Rheumatol. 2004 May;31(5):920-4.
41. Hoffman IE, Demetter P, Peeters M, De Vos M, Mielants H, Veys EM, et al. Anti-saccharomyces cerevisiae IgA antibodies are raised in ankylosing spondylitis and undifferentiated spondyloarthropathy. Ann Rheum Dis. 2003 May;62(5):455–9.
42. Torok HP, Glas J, Gruber R, Brumberger V, Strasser C, Kellner H, et al. Inflammatory bowel disease-specific autoantibodies in HLA-B27-associated spondyloarthropathies: increased prevalence of ASCA and pANCA. Digestion. 2004;70(1):49–54.
43. Klingberg E, Carlsten H, Hilme E, Hedberg M, Forsblad-d’Elia H. Calprotectin in ankylosing spondylitis—frequently elevated in feces, but normal in serum. Scand J Gastroenterol. 2012 Apr;47(4):435-44.
44. Maxwell LJ, Zochling J, Boonen A, Singh JA, Veras MM, Tanjong Ghogomu E, et al. TNF-alpha inhibitors for ankylosing spondylitis. Cochrane Database Syst Rev. 2015 Apr 18;4:CD005468.
45. Stoll ML, Kumar R, Morrow CD, Lefkowitz EJ, Cui X, Genin A, et al. Al¬tered microbiota associated with abnormal humoral immune responses to commensal organisms in enthesitis-related arthritis. Arthritis Res Ther. 2014 Nov;16(6):486.
46. Colman RJ, Rubin DT. Fecal microbiota transplantation as therapy for in¬flammatory bowel disease: a systematic review and meta-analysis. J Crohns Colitis. 2014 Dec;8(12):1569-81.
47. Kohlo KL, Korpela K, Jaakkola T, Pichai MV, Zoetendal EG, Salonen A, et al. Fecal microbiota in pediatric inflammatory bowel disease and its relation to inflammation. Am J Gastroenterol. 2015 Jun;110(6):921-30.
48. Karimi O, Peña AS. Indications and challenges of probiotics, prebiotics, and symbiotics in the management of arthralgias and spondyloarthropathies in inflammatory bowel disease. J Clin Gastroenterol. 2008 Sep;42 Suppl 3 Pt 1:S136-41.
49. Lee J, Rachmilewitz D, Raz E. Homeostatic effects of TLR9 signaling in experimental colitis. Ann N Y Acad Sci. 2006 Aug;1072:351-5.
How to Cite
Authors who publish with this journal agree to the following terms:
- The Author retains copyright in the Work, where the term “Work” shall include all digital objects that may result in subsequent electronic publication or distribution.
- Upon acceptance of the Work, the author shall grant to the Publisher the right of first publication of the Work.
- The Author shall grant to the Publisher and its agents the nonexclusive perpetual right and license to publish, archive, and make accessible the Work in whole or in part in all forms of media now or hereafter known under a Creative Commons Attribution 4.0 International License or its equivalent, which, for the avoidance of doubt, allows others to copy, distribute, and transmit the Work under the following conditions:
- Attribution—other users must attribute the Work in the manner specified by the author as indicated on the journal Web site; with the understanding that the above condition can be waived with permission from the Author and that where the Work or any of its elements is in the public domain under applicable law, that status is in no way affected by the license.
- The Author is able to enter into separate, additional contractual arrangements for the nonexclusive distribution of the journal's published version of the Work (e.g., post it to an institutional repository or publish it in a book), as long as there is provided in the document an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post online a prepublication manuscript (but not the Publisher’s final formatted PDF version of the Work) in institutional repositories or on their Websites prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work. Any such posting made before acceptance and publication of the Work shall be updated upon publication to include a reference to the Publisher-assigned DOI (Digital Object Identifier) and a link to the online abstract for the final published Work in the Journal.
- Upon Publisher’s request, the Author agrees to furnish promptly to Publisher, at the Author’s own expense, written evidence of the permissions, licenses, and consents for use of third-party material included within the Work, except as determined by Publisher to be covered by the principles of Fair Use.
- The Author represents and warrants that:
- the Work is the Author’s original work;
- the Author has not transferred, and will not transfer, exclusive rights in the Work to any third party;
- the Work is not pending review or under consideration by another publisher;
- the Work has not previously been published;
- the Work contains no misrepresentation or infringement of the Work or property of other authors or third parties; and
- the Work contains no libel, invasion of privacy, or other unlawful matter.
- The Author agrees to indemnify and hold Publisher harmless from the Author’s breach of the representations and warranties contained in Paragraph 6 above, as well as any claim or proceeding relating to Publisher’s use and publication of any content contained in the Work, including third-party content.
Enforcement of copyright
The IJMS takes the protection of copyright very seriously.
If the IJMS discovers that you have used its copyright materials in contravention of the license above, the IJMS may bring legal proceedings against you seeking reparation and an injunction to stop you using those materials. You could also be ordered to pay legal costs.
If you become aware of any use of the IJMS' copyright materials that contravenes or may contravene the license above, please report this by email to firstname.lastname@example.org
If you become aware of any material on the website that you believe infringes your or any other person's copyright, please report this by email to email@example.com