Frontiers in Immunology (Sep 2023)

Toxin exposure and HLA alleles determine serum antibody binding to toxic shock syndrome toxin 1 (TSST-1) of Staphylococcus aureus

  • Stefan Weiss,
  • Stefan Weiss,
  • Silva Holtfreter,
  • Tanja C. Meyer,
  • Frieder Schmiedeke,
  • Clemens Cammann,
  • Marcus Dörr,
  • Marcus Dörr,
  • Stephan B. Felix,
  • Stephan B. Felix,
  • Hans J. Grabe,
  • Georg Homuth,
  • Christian Kohler,
  • Cedric Mahncke,
  • Stephan Michalik,
  • Matthias Nauck,
  • Matthias Nauck,
  • Nele Friedrich,
  • Nele Friedrich,
  • Stefanie Samietz,
  • Henry Völzke,
  • Henry Völzke,
  • Uwe Völker,
  • Uwe Völker,
  • Barbara M. Bröker

DOI
https://doi.org/10.3389/fimmu.2023.1229562
Journal volume & issue
Vol. 14

Abstract

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Life-threatening toxic shock syndrome is often caused by the superantigen toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus. A well-known risk factor is the lack of neutralizing antibodies. To identify determinants of the anti-TSST-1 antibody response, we examined 976 participants of the German population-based epidemiological Study of Health in Pomerania (SHIP-TREND-0). We measured anti-TSST-1 antibody levels, analyzed the colonization with TSST-1-encoding S. aureus strains, and performed a genome-wide association analysis of genetic risk factors. TSST-1-specific serum IgG levels varied over a range of 4.2 logs and were elevated by a factor of 12.3 upon nasal colonization with TSST-1-encoding S. aureus. Moreover, the anti-TSST-1 antibody levels were strongly associated with HLA class II gene loci. HLA-DRB1*03:01 and HLA-DQB1*02:01 were positively, and HLA-DRB1*01:01 as well as HLA-DQB1*05:01 negatively associated with the anti-TSST-1 antibody levels. Thus, both toxin exposure and HLA alleles affect the human antibody response to TSST-1.

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