TY - BOOK

T1 - Detection of staphylococcal enterotoxins in patients with rheumatoid arthritis or closed fracture

AU - Grace, Laura

PY - 2016

Y1 - 2016

N2 - 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 thepyrogenic toxin superantigen family (PTSAg). To develop a novel mass spectrometrymethod 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 amixture of genetic, immunological and environmental factors. A T-cell immune responseto 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 ofchronic, autoimmune conditions. Potential pathogenic mechanisms include the hygienehypothesis and molecular mimicry. Due to the widespread prevalence of RA, it has beenhypothesised that the pathogenesis could involve a common bacterium. In RA, onepotential bacterial candidate that has been suggested is S.aureus.Current published data averages the presence of S.aureus in the general population at30% (nasal/nasopharyngeal swabs). However, our unpublished data suggests immunecomplexes containing S.aureus antigens are detectable in urine. xiiMethods: Mid-stream urine samples were collected from the rheumatology andorthopaedic departments of the Royal Lancaster Infirmary (RLI), UK. Urine sampleswere analysed by western blot and mass spectrometry.Results: 56.4% of RA patients showed the presence of at least one staphylococcal toxin intheir urine compared with 27.1% of fracture patients.Conclusion: Our work demonstrates an increased presence of bacterial toxins in urinefrom RA patients, compared to the fracture controls and the current literature. This studyis the first to demonstrate the presence of common staphylococcal enterotoxins in RApatient 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 anindividual’s likelihood of getting RA; are those people with RA more likely to haveS.aureus infections due to their immunological state? The presence of S.aureus in RApatient tissues warrants further investigation to determine if it is causative of, or a resultof RA diagnosis.

AB - 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 thepyrogenic toxin superantigen family (PTSAg). To develop a novel mass spectrometrymethod 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 amixture of genetic, immunological and environmental factors. A T-cell immune responseto 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 ofchronic, autoimmune conditions. Potential pathogenic mechanisms include the hygienehypothesis and molecular mimicry. Due to the widespread prevalence of RA, it has beenhypothesised that the pathogenesis could involve a common bacterium. In RA, onepotential bacterial candidate that has been suggested is S.aureus.Current published data averages the presence of S.aureus in the general population at30% (nasal/nasopharyngeal swabs). However, our unpublished data suggests immunecomplexes containing S.aureus antigens are detectable in urine. xiiMethods: Mid-stream urine samples were collected from the rheumatology andorthopaedic departments of the Royal Lancaster Infirmary (RLI), UK. Urine sampleswere analysed by western blot and mass spectrometry.Results: 56.4% of RA patients showed the presence of at least one staphylococcal toxin intheir urine compared with 27.1% of fracture patients.Conclusion: Our work demonstrates an increased presence of bacterial toxins in urinefrom RA patients, compared to the fracture controls and the current literature. This studyis the first to demonstrate the presence of common staphylococcal enterotoxins in RApatient 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 anindividual’s likelihood of getting RA; are those people with RA more likely to haveS.aureus infections due to their immunological state? The presence of S.aureus in RApatient tissues warrants further investigation to determine if it is causative of, or a resultof RA diagnosis.

M3 - Doctoral Thesis

PB - Lancaster University

ER -