Background Rheumatoid arthritis (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 pyrogenic toxin superantigens (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. Previously, Porphyromonas gingivalis, a periodontal pathogen, has been suggested due to its ability to citrullinate proteins. In RA one potential bacterial candidate that has been suggested is Staphylococcus aureus.
Current published data averages the presence of S.aureus at 30% in the general population from nasopharyngeal swabs1. Furthermore, our unpublished data suggests immune complexes containing S.aureus antigens are detectable in urine.
Objectives To investigate the presence of staphylococcal enterotoxins B and C (SEB/SEC), toxic shock syndrome toxin 1 (TSST-1) and alpha haemolysin (AH) in the urine of patients with RA to support the hypothesis that they may play a role in RA.
Methods Following ethical approval, mid-stream urine samples were obtained from patients with RA and a control group (patients with closed fractures). Both populations had no active infection(s) and were recruited from British Rheumatology and Orthopaedic departments in the same hospital. Samples were collected and processed aseptically, then analysed by western blot using commercially available primary (sheep) antibodies to SEB, SEC, TSST-1 and AH; and a rabbit anti-sheep HRP conjugated secondary antibody.
Results The RA population comprises 110 females and 38 males aged 25–90 (median =65–74). The control population comprises 18 females and 9 males (median age =55–64) to date.
Western blot analysis demonstrated the presence of AH/SEB/SEC in 81 of 148 (54.7%) RA patient urine samples and 9 of 27 (33.3%) control samples.
Conclusions Our work demonstrates the presence of bacterial toxins in urine from RA patients, with 54.7% demonstrating the presence of at least one staphylococcal toxin. 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.
We also show that S.aureus toxins are present in urine of nearly 2 times more of the RA population than the general population. 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.
Acknowledgement Funding provided by UHMB NHS Foundation Trust.
Disclosure of Interest None declared
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