Targeting HLA-B27 Misfolding as a Potential Therapeutic Treatment of Ankylosying Spondylitis

HLA-B27 is a Major Histocompatibility Complex (MHC) class I molecule whose predominant function is the presentation of short 8-10 amino acid long peptides to cytotoxic CD8+T cells. HLA-B27 exhibits a strong association with a group of inflammatory arthritic diseases referred to as the spondyloarthropathies (SpAs) [1]. The SpAs are characterized by inflammation at the entheses, followed by skeletal fusion, which predominantly occurs at the sacroiliac joint and along the vertebral column. In addition, the SpAs are characterized by inflammation of other organ systems such as the gastrointestinal tract, which is perhaps the next most common inflammatory lesion, manifesting as either a ‘Crohns’ or ‘colitis’ like disease [2]. It remains unknown why these specific sites are targets for disease development but it has been proposed that exposure to mechanical stress could be a contributory factor [3].