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Current Rheumatology Reports

Erschienen in:

01.10.2019 | Spondyloarthritis (M Khan, Section Editor)

The Pathogenesis of Ankylosing Spondylitis: an Update

verfasst von: Susanne Juhl Pedersen, Walter P. Maksymowych

Erschienen in: Current Rheumatology Reports | Ausgabe 10/2019

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Abstract

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.

Summary

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.

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Titel: The Pathogenesis of Ankylosing Spondylitis: an Update
verfasst von: Susanne Juhl Pedersen
Walter P. Maksymowych
Publikationsdatum: 01.10.2019
Verlag: Springer US
Erschienen in: Current Rheumatology Reports / Ausgabe 10/2019
Print ISSN: 1523-3774
Elektronische ISSN: 1534-6307
DOI: https://doi.org/10.1007/s11926-019-0856-3

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