Grace, Laura (2016) Detection of staphylococcal enterotoxins in patients with rheumatoid arthritis or closed fracture. PhD thesis, UNSPECIFIED.
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Abstract
Aim: To develop protocols to digest staphylococcal enterotoxins B and C (SEB/SEC), toxic shock syndrome toxin 1 (TSST-1) and alpha haemolysin (AH), members of the pyrogenic toxin superantigen family (PTSAg). To develop a novel mass spectrometry method to analyse and compare urine samples from patients with rheumatoid arthritis (RA) and orthopaedic fracture patients for the presence of Staphylococcus aureus. Background: RA is a disease of unknown etiology; with a pathogenesis that is due to a mixture of genetic, immunological and environmental factors. A T-cell immune response to the presence of PTSAgs in the joints of RA patients has previously been described. A link has been proposed between pathogenic micro-organisms and the development of chronic, autoimmune conditions. Potential pathogenic mechanisms include the hygiene hypothesis and molecular mimicry. Due to the widespread prevalence of RA, it has been hypothesised that the pathogenesis could involve a common bacterium. In RA, one potential bacterial candidate that has been suggested is S.aureus. Current published data averages the presence of S.aureus in the general population at 30% (nasal/nasopharyngeal swabs). However, our unpublished data suggests immune complexes containing S.aureus antigens are detectable in urine. xii Methods: Mid-stream urine samples were collected from the rheumatology and orthopaedic departments of the Royal Lancaster Infirmary (RLI), UK. Urine samples were analysed by western blot and mass spectrometry. Results: 56.4% of RA patients showed the presence of at least one staphylococcal toxin in their urine compared with 27.1% of fracture patients. Conclusion: Our work demonstrates an increased presence of bacterial toxins in urine from RA patients, compared to the fracture controls and the current literature. This study is the first to demonstrate the presence of common staphylococcal enterotoxins in RA patient urine, raising the question of what role they may have in the disease pathogenesis, given that these patients have no active infections. This raises questions of whether the bacteria and their toxins are involved in an individual’s likelihood of getting RA; are those people with RA more likely to have S.aureus infections due to their immunological state? The presence of S.aureus in RA patient tissues warrants further investigation to determine if it is causative of, or a result of RA diagnosis.