The Pathogenesis of Ankylosing Spondylitis: an Update

  • Susanne Juhl PedersenEmail author
  • Walter P. Maksymowych
Spondyloarthritis (M Khan, Section Editor)


Purpose of Review

Ankylosing spondyloarthritis (AS) is a chronic inflammatory disease that involves the axial joints and entheses. Extra-spinal manifestations such as anterior uveitis, psoriasis, and colitis also occur frequently. This review on the pathogenesis of AS includes an update on the recent discoveries within the field.

Recent Findings

HLA-B*27 is still considered of major importance in the pathogenesis, and it has recently been shown to profoundly affect the gut microbiome and its metabolites and the handling of bacteria during infection. Biochemical and biophysical properties of HLA-B*27 influence its ability to misfold, to induce an endoplasmic reticulum stress response, and to promote autophagy/unfolded protein responses (UPR). HLA-B*27 free heavy chains may induce inflammation through T cells, NK cells, and myeloid cells. Induction of UPR genes results in release of tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-23, and interferon-γ and increase in T helper (Th) 17 cells. Several other HLA-B and non-B molecules have been associated with AS, although their role in the pathogenesis is unknown.


Genotypes of endoplasmic reticulum aminopeptidases (ERAP) 1 and 2 have been associated with alterations in the antigenic pool expressed by HLA-B*27 molecules. In the gut, innate immune cells type 3 (ILC3) influence T cell expression of IL-17 and IL-22. Gamma-delta (γ/δ) T cells are induced by IL-23 to produce IL-17. IL-7 induces mucosa-associated invariant T (MAIT) cells to produce IL-17. Besides the microbiome, zonulin may be important through its effects on the permeability of tight junctions in the intestinal epithelial barrier.


Ankylosing spondylitis Pathogenesis HLA-B*27 Genes Microbiome Immunology 


Compliance with Ethical Standards

Conflict of Interest

WPM has received research support and/or consultancy/speaker fees from Abbvie, Boehringer, Celgene, Eli-Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, and UCB. SJP has received honoraria for speaking from MSD, Pfizer, AbbVie, Novartis, and UCB, has been an advisory board member for AbbVie and Novartis, and has received research support from AbbVie, MSD, and Novartis.

Human and Animal Rights and Informed Consent

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


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Copenhagen Center for Arthritis Research (COPECARE), Center for Rheumatology and Spine DiseaseRigshospitaletGlostrupDenmark
  2. 2.Department of MedicineUniversity of AlbertaEdmontonCanada

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