Abstract
The mechanism by which HLA-B*27 predisposes to spondyloarthritis remains unresolved. Arthritogenic peptides have not been defined in humans and are not involved in experimental models of spondyloarthritis. Aberrant properties of HLA-B*27 can activate the IL-23/IL-17 axis in HLA-B*27 transgenic rats and humans. In HLA-B*27-independent rodent models, spondyloarthritis can be driven by IL-23 triggering entheseal-resident CD4-/CD8- T cells or CD4+ Th17 T cells. These findings point toward noncanonical mechanisms linking HLA-B*27 to the disease and provide a potential explanation for HLA-B*27-negative spondyloarthritis. Gut microbial dysbiosis may be important in the development of spondyloarthritis. HLA-B*27-induced changes in gut microbiota are complex and suggest an ecological model of dysbiosis in rodents. The importance of the IL-23/IL-17 axis in ankylosing spondylitis has been demonstrated by studies showing efficacy of IL-17. Although deciphering the precise role(s) of HLA-B*27 in disease requires further investigation, considerable progress has been made in understanding this complex relationship.
Original language | English (US) |
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Pages (from-to) | 797-815 |
Number of pages | 19 |
Journal | Best Practice and Research: Clinical Rheumatology |
Volume | 31 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2017 |
Externally published | Yes |
Keywords
- Ankylosing spondylitis
- Arthritogenic peptides
- Autophagy
- Dysbiosis
- Endoplasmic reticulum-associated aminopeptidase-1 (ERAP1)
- Endoplasmic reticulum-associated degradation (ERAD)
- Inflammatory bowel disease
- Microbiota
- Protein misfolding
- Spondyloarthritis
ASJC Scopus subject areas
- Rheumatology