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

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1229562

DOI=10.3389/fimmu.2023.1229562

ISSN=1664-3224

ABSTRACT=<p>Life-threatening toxic shock syndrome is often caused by the superantigen toxic shock syndrome toxin-1 (TSST-1) produced by <italic>Staphylococcus aureus</italic>. 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 <italic>S. aureus</italic> 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 <italic>S. aureus</italic>. 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.</p>