Bowness Group | Immunology of Ankylosing Spondylitis

Botnar

Our main research goal is to understand the molecular mechanisms causing inflammation, particularly in Ankylosing Spondylitis and other forms of inflammatory arthritis including Psoriatic Arthritis, and to translate this understanding into new patient therapy.

Ankylosing spondylitis (AS) is a chronic condition which affects primarily the joints of the lower back. 'Ankylosing' means stiffening and 'spondylitis' means inflammation of the spine; people with this condition suffer from back pain and stiffness, fatigue, and pain and swelling in other parts of the body. Currently, there is no cure for AS, but some treatments relieve symptoms of the condition and may possibly prevent its progression.

Development of a number of common forms of inflammatory arthritis (the spondyloarthritides), which include Ankylosing Spondylitis is strongly associated with possession of the Human Leukocyte Antigen (HLA) class I allele HLA-B27.

Despite extensive studies, the pathogenic role of HLA-B27 in the spondyloarthritides remains unknown.

We hypothesize that the role of HLA-B27 in spondyloarthropathy stems from its function in antigen presentation, either in peptide selection and binding or in other aspects of its cell biology. We first described the ability of HLA-B27 to form homodimers and have shown that these homodimers are present on the surface of spondyloarthritis patients' cells as well as in B27 transgenic models of disease, and identified cellular receptors for B27 homodimers including KIR3DL2.

We are using Single cell techniques including scRNAseq FACS and Cytof to investigate immune responses in AS and related Spondyloarthitis (SpA).

We have investigated the role of "Type 17" immune responses in SpA and identified potential new therapeutic targets for translation into treatment for these conditions.