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Explore how immune dysregulation drives inflammation in patients with axSpA

The role of different immune cells in axSpA

A dysregulated immune system has many moving parts that act to create the chronic inflammation indicative of disease pathology in SpA. Several types of adaptive and innate immune cells play key roles in mediating inflammation.1-4

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  • Innate
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Cytokine dysregulation in axSpA

Following an injury in the entheses, local cells produce chemo-attractants as mediators of inflammation. This causes local immune cells and innate lymphocytes to secrete cytokines. They enter the circulation and recruit T cells and innate immune cells into the inflamed tissue and produce pro-inflammatory and regulatory cytokines in the entheseal site. In a balanced state, this results in regulated and effective repair mechanisms. However, in axSpA, this process is not balanced, and cytokine dysregulation occurs.1,11-13

Cytokine dysregulation is characterized by an excess of inflammatory and/or a depletion of regulatory cytokines, which can lead to pathogenic bone formation. The cytokine balance is influenced by genetic factors, the microbiome, as well as environmental factors, many of which are still unknown.11,13

Cytokine dysregulation in axSpA

Genetic risk factors

One of the key genetic risk factors in axSpA is the strong association of AS with inheritance of the HLA allele B27 (HLA-B27).14 HLA-B27 may contribute to inflammatory cytokine production in axSpA through the unfolded protein response.14

Influence of the microbiome

In axSpA, there is an association between the microbiome and disease development.15 A large proportion of IL-17 producing and T regulatory cells are derived from the gut and a different microbiome signature has been observed in patients with AS compared with healthy individuals.15

Learn more about key cytokines that could be dysregulated, leading to inflammation

Gaze upon the Gallery of Cytokines


Bone damage

Explore the complex pathogenic processes that can lead to bone damage in patients with axSpA.

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Overview and role of cytokines

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  2. Rezaiemanesh A, Abdolmaleki M, Abdolmohammadi K, et al. Immune cells involved in the pathogenesis of ankylosing spondylitis. Biomed Pharmacother. 2018;100:198-204. doi:10.1016/j.biopha.2018.01.108
  3. Rosine N, Miceli-Richard C. Innate cells: the alternative source of IL-17 in axial and peripheral spondyloarthritis?. Front Immunol. 2021;11:553742. Published 2021. doi:10.3389/fimmu.2020.553742
  4. Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391(10136):2273-2284. doi:10.1016/S0140-6736(18)30830-4
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  9. Shevyrev D, Tereshchenko V. Treg Heterogeneity, Function, and Homeostasis. Front Immunol. 2020;10:3100. Published 2020. doi:10.3389/fimmu.2019.03100
  10. Lai NL, Zhang SX, Wang J, et al. The proportion of regulatory T cells in patients with ankylosing spondylitis: A Meta-Analysis. J Immunol Res. 2019;2019:1058738. Published 2019. doi:10.1155/2019/1058738
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  12. McGonagle DG, McInnes IB, Kirkham BW, et al. The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies. Ann Rheum Dis. 2019;78:1167–1178
  13. Watad A, Rowe H, Russell T, et al. Normal human enthesis harbours conventional CD4+ and CD8+ T cells with regulatory features and inducible IL-17A and TNF expression. Ann Rheum Dis. 2020;79(8):1044-1054. doi:10.1136/annrheumdis-2020-217309
  14. Simone D, Al Mossawi MH, Bowness P. Progress in our understanding of the pathogenesis of ankylosing spondylitis. Rheumatology (Oxford). 2018;57(suppl_6):vi4-vi9. doi:10.1093/rheumatology/key001
  15. Clemente JC, Manasson J, Scher JU. The role of the gut microbiome in systemic inflammatory disease. BMJ. 2018;360:j5145. doi:10.1136/bmj.j5145
  16. Siebert S, Millar NL, McInnes IB. Why did IL-23p19 inhibition fail in AS: a tale of tissues, trials or translation? Ann Rheum Dis. 2019;78(8):1015-1018. doi:10.1136/annrheumdis-2018-213654