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

Front Immunol. 2023 Sep 4:14:1229562. doi: 10.3389/fimmu.2023.1229562. eCollection 2023.

Abstract

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.

Keywords: GWA; HLA; MHC; Staphylococcus aureus; TSST-1; antibody; superantigen; toxic shock syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Genome-Wide Association Study
  • Humans
  • Shock, Septic* / genetics
  • Staphylococcal Infections* / genetics
  • Staphylococcus aureus
  • Superantigens / genetics

Substances

  • enterotoxin F, Staphylococcal
  • Superantigens

Grants and funding

This study was supported by grants of the DFG (Deutsche Forschungsgemeinschaft) with the CRC TR 34 (project C16; UV, BB, TM) and by the European Social Fund, Card-ii-Omics, ESF/14-BMA55-0037/16 (UV, BB, SH, SM, SF). SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genomewide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania. The genome-sequencing in this study was conducted by the Helmholtz Zentrum München (Deutsches Forschungszentrum für Gesundheit und Umwelt) with funds from the DZHK OMICs initiative (81X1600102; MD, NF, GH, MN, UV, SW). The genome-sequencing in this study was further supported by the EU-JPND funding for the BRIDGET project (01ED1615; HG).