The Immunopathogenesis of HLA B27-associated Spondylarthritis and Acute Anterior Uveitis

HLA-B27 is a Class I Major Histocompatability Molecule that is highly prevalent in patients with Acute Anterior Uveitis (AAU) and Seronegative Arthritis (SNA). Despite over 40 years of research, the pathogenic mechanism of HLA-B27-related disease remains elusive. The bacterium Chlamydia trachomatis has been implicated in disease pathogenesis, whereby molecular mimicry results in an antigen derived from the microorganism to cross-react with a molecule in the host, triggering an inflammatory response. Lumican is an extracellular molecule that is found in both the eye and joint and has important structural, functional and immunological functions. This study showed that lumican was present in the aqueous humor of eyes in patients with AAU. Furthermore, immunohistochemical studies did show it is present in the iris and associated blood vessels, the site of inflammation of AAU. Additionally it was found that lumican has sequence homology with the cell wall component of C. trachomatis. Given these properties of lumican, this study aimed to examine cellular responses to peptide antigens derived from C. trachomatis and lumican in the peripheral blood of patients with AAU and SNA and to compare the prevalence of positive serology to Chlamydia in patients who are HLA-B27-positive to those who are HLA-B27-negative. It was shown that HLA-B27-positive patients with both AAU and SNA were more likely to display positive IgG serology to Chlamydia compared to healthy controls, suggesting that past exposure to Chlamydia is important in disease pathogenesis. ELISPOT assays were employed to measure cellular responses to antigens. They showed that HLA-B27 patients had a higher percentage of responders to groups of peptides derived from C. trachomatis, lumican and other extracellular matrix components than both HLA-B27 negative patients and healthy controls. Using flow cytometric methods CD4+ and CD8+ T cell responses were measured which indicated that patients with HLA-B27-related disease responded more to some antigens, and these reached statistical significance when CD8+ T cell responses to some antigens were measured. In summary, this study does suggest that cross-reactivity between a bacterial trigger and a self-protein may be important in disease pathogenesis, lending weight to the hypothesis that there exists an arthritogenic or uveitogenic peptide.

Grantor dc:publisher

UNSW, Sydney

Year dc:date

2016

Author dc:creator

• Amjadi, Shahriar

• Arthritis.
• Uveitis.
• HLA-B27.
• Seronegative arthritis.
• Anterior uveitis.
• Cell-mediated immunity.
• Molecular mimicry.
• Autoimmunity.
• Autoinflammation.
• Chlamydia
• Lumican.
• Serology.
• Spondyloarthritis.
• Spondyloarthropathy.
• Ankylosing spondylitis.
• Acute anterior uveitis.

Statement dc:rights

• open access
• CC BY-NC-ND 3.0
• free_to_read

Licence

• https://purl.org/coar/access_right/c_abf2
• https://creativecommons.org/licenses/by-nc-nd/3.0/au/

Language dc:language

EN

Identifier

https://doi.org/10.26190/unsworks/3049

OAI identifier oai:identifier

oai:unsworks.library.unsw.edu.au:1959.4/56921