New developments in our understanding of ankylosing spondylitis pathogenesis

Abstract

Ankylosing spondylitis (AS) is a common immune-mediated inflammatory arthritis with a strong genetic predisposition. We review recent data from genetic and animal studies highlighting the importance of Type 17 immune responses. Furthermore, the efficacy (or lack thereof) of different anti-cytokine monoclonal antibodies has highlighted the diversity of Type 17 immune cells and cytokines critical to AS and related spondyloarthritis pathogenesis. Recent studies have strongly implicated the gut microbiome in AS. Finally, we propose that the local metabolic environment of the joint may have a key role in driving AS, and present a novel model of AS pathogenesis.

Keywords: ankylosing spondylitis; immunometabolism; microbiome; spondyloarthritis.

Figure 1

Key factors in ankylosing spondylitis (AS) pathogenesis.

Figure 2

Model showing interplay of factors affecting CD4⁺ T‐cell differentiation and their likely roles in ankylosing spondylitis (AS) pathogenesis. We include speculation about links between the metabolic environment and T‐cell plasticity. Existing or potential drug targets are indicated with a syringe symbol next to them.