Investigating the cellular causes of HLA-B27 associated spondyloarthritis
Ankylosing spondylitis (AS) is a common form of inflammatory arthritis. It is a highly heritable, polygenic disease for which the strongest genetic association is with the MHC I molecule HLA-B*27. Despite this and other associations with genes of the innate and adaptive immune systems, the cellular and molecular causes of the disease remain enigmatic. Normally first detected in sacroiliac joints, AS is typified by enthesitis – inflammation at sites of muscle attachment to bone - which can lead to abnormal bone growth. Outside the joints, other sites subject to repeated mechanical stress are also prone to inflammation in AS. Inflammation of the eye, for example, is very common in AS patients and is also independently associated with HLA-B27. In one possible model, HLA-B27 mediated inflammation at entheseal (or entheseal-like sites) may involve the dysregulation of a homeostatic tissue repair circuit. In work recently funded by Versus Arthritis we are leading a single-cell genomics-based study of biopsy samples in order to discover and characterize the cells that cause and respond to inflammation in HLA-B27 positive AS patients. We aim to help patients by aiding early disease detection and by providing a rational basis for development of curative therapeutics. This work is made possible by a close partnership between a team of scientists and clinicians that include Professor Paul Bowness, Dr Sri Sharma and Dr Jonathan Sherlock and Professor Chris Buckley.