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Abstract Number: 2575

The Presence of Staphylococcal Toxins in the Urine of Patients with Rheumatoid Arthritis

Laura Grace1, Marwan Bukhari2, Robert Lauder3, Lisa Bishop4,5 and Adam Taylor1, 1Lancaster Medical School, Lancaster University, Lancaster, United Kingdom, 2Royal Lancaster Infirmary, Lancaster, United Kingdom, 3Biomedical & Life Sciences, Lancaster University, Lancaster, United Kingdom, 4Biomedical and Life Sciences, Lancaster University, Lancaster, United Kingdom, 5University Hopsitals of Morecambe Bay NHS Trust, Lancaster, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: Infection, pathogenesis and rheumatoid arthritis (RA)

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Session Information

Date: Tuesday, November 15, 2016

Title: Rheumatoid Arthritis – Human Etiology and Pathogenesis - Poster III

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:  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 data has found immune complexes containing S.aureus antigens are detectable in urine(ref).  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 attending an orthopaedic clinic). 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 148 patients (74% females) The control population comprises 70 patients (52% female ). Mean age was older in the RA group (63 vs 58 years p<0.01) results of the toxins and differences between cases and controls are shown in table 1 (below)

Table 1 Descriptive characteristics of the population(s).
All characteristics
All
(n=219)
RA
(n=149)
Fracture (n=70)
Difference
P value
Female (%)
162 (74.0)
110 (73.8)
52 (74.3)
 
Mean Age (SD)
62.1 (14.3)
63.9 (12.4)
58.1 (17.1)
<0.0045
Positive AH (%)
73(33.3%)
69(46.3%)
4 (5.7%)
P<0.001
Positive SEB (%)
54 (24.7%)
40 (26.9%)
14 (20%)
P=0.27
Positive SEC (%)
71 (32.4%)
57 (38.23
14(20%)
P=0.007
Positive TSST (%)
0 (0)
0 (0)
0 (0)
.
Any Toxin (%)
103 (47.0)
84 (56.4)
19 (27.1)
 
 
The odds of being toxin positive for each was AH 13.7 (95%CI 4.7,39.6), SEB 1.34 (95%CI 0.66,2.71) and SEC 2.4 (95%CI 1.22,4.8). The odds of any toxin being positive was 3.5 (95%CI 1.9,6.4) and this remained significant after adjusting for age and gender
 

Conclusion:  Our work demonstrates the presence of bacterial toxins in urine from RA patients, with 56% demonstrating the presence of at least one staphylococcal toxin. We also show that S.aureus toxins are differentially expressed in this population. The pathological basis of this finding is not clear.

ref  Ann Rheum Dis2016;75(Suppl2): 930


Disclosure: L. Grace, None; M. Bukhari, Merck, Roche, Mennarini, Amgen, Pfizer, Eli-Lilly, Sanofi-Aventis , Abbvie, 8; R. Lauder, None; L. Bishop, None; A. Taylor, None.

To cite this abstract in AMA style:

Grace L, Bukhari M, Lauder R, Bishop L, Taylor A. The Presence of Staphylococcal Toxins in the Urine of Patients with Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-presence-of-staphylococcal-toxins-in-the-urine-of-patients-with-rheumatoid-arthritis/. Accessed .
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