Ankylosing spondylitis (AS) is a chronic systemic rheumatic disorder, which is characterised by sacroiliitis, enthesopathy, and a variety of extra-articular manifestations. Despite having the strongest association ever described with a tissue antigen, HLA B27, the pathogenesis of AS remains poorly understood. Immunoregulatory genes and Gram-negative gut bacteria are thought to be important in disease expression. It is now known that mammalian immune response to Gram-negative bacteria is mediated by Toll-like receptor 4 (TLR4), a pattern recognition receptor. Two cosegregating missense mutations have recently been described in TLR4 that lead to a diminished host response to Gram-negative bacteria. We hypothesise that TLR4 mutations occur with an increased frequency in HLA B27-positive individuals who develop AS than in healthy HLA B27-positive controls, and allow increased survival and the systemic distribution of Gram-negative gut bacteria to the joints. This study aims to compare the frequency of two common TLR4 mutations (Asp299Gly, and Thr399Ile) between AS patients and HLA B27 healthy controls.