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Rheumatology Advance Access originally published online on April 4, 2007
Rheumatology 2007 46(6):1029-1033; doi:10.1093/rheumatology/kem022
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Staphylococcal toxic-shock-syndrome-toxin-1 as a risk factor for disease relapse in Wegener's granulomatosis

E. R. Popa*, C. A. Stegeman1,*, W. H. Abdulahad, B. van der Meer, J. Arends2, W. M. Manson2, N. A. Bos3, C. G. M. Kallenberg and J.-W. Cohen Tervaert4

Department of Clinical Immunology, 1Department of Nephrology, 2Department of Medical Microbiology, 3Department of Cell Biology, University of Groningen, University Medical Centre Groningen and 4Department of Clinical and Experimental Immunology, University Hospital of Maastricht, The Netherlands.

Correspondence to: Eliane R. Popa, Department of Medical Biology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. E-mail: e.popa{at}med.umcg.nl


   Abstract

Objectives. Nasal carriage of Staphylococcus aureus constitutes a risk factor for disease exacerbation in Wegener's granulomatosis (WG). We hypothesized that staphylococcal superantigens (SAg) are a determinant of S. aureus-related risk for disease relapse in WG.

Methods. In a retrospective longitudinal cohort study in 62 WG patients, we investigated the presence of the staphylococcal SAg genes sea, seb, sec, sed, see, tsst-1 and eta in S. aureus strains isolated from WG patients during an observation period of seven years. Subsequently, we assessed whether relapses of WG were associated with the presence of SAg-positive staphylococci.

Results. Of 1718 swab cultures analysed, 709 (41.2%) were S. aureus-positive. Fifty-one patients carried S. aureus, of whom 37 (72.5%) patients carried at least one SAg-positive S. aureus strain. Of the 709 S. aureus-positive cultures, 326 (46%) contained at least one SAg gene. Except for see, all assessed SAg genes were detected. sea was found most frequently, followed by sec, tsst-1 and eta and finally, by sed and seb. Using a multivariate, time-dependent Cox regression analysis we found that the presence of S. aureus was associated with relapses of WG (RR 3.2; 95% CI 1.2–8.4). The risk for relapse was modulated by the presence and type of SAg, with tsst-1 being associated with an increased risk for relapse (RR 13.3, 95% CI 4.2–42.6).

Conclusion. The risk for relapse of WG increases with the presence of tsst-1-positive S. aureus. Eradication of tsst-1-positive S. aureus in WG may show whether disease relapses can be prevented.

KEY WORDS: Wegener's granulomatosis, Vasculitis, S. aureus, Superantigens, Relapse, TSST-1, PCR


*ER Popa and CA Stegeman equally contributed to this work.

Submitted 17 July 2006; revised version accepted 12 January 2007.
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