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

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

doi:10.3389/fimmu.2023.1229562

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.

Authors

Stefan Weiss^{1

2}, Silva Holtfreter³, Tanja C Meyer¹, Frieder Schmiedeke³, Clemens Cammann⁴, Marcus Dörr^{2

5}, Stephan B Felix^{2

5}, Hans J Grabe⁶, Georg Homuth¹, Christian Kohler⁴, Cedric Mahncke⁴, Stephan Michalik¹, Matthias Nauck^{2

7}, Nele Friedrich^{2

7}, Stefanie Samietz⁸, Henry Völzke^{2

9}, Uwe Völker^{1

2}, Barbara M Bröker³

Affiliations

¹ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
² German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald, Greifswald, Germany.
³ Institute of Immunology, University Medicine Greifswald, Greifswald, Germany.
⁴ Friedrich Loeffler Institute of Medical Microbiology, University Medicine Greifswald, Greifswald, Germany.
⁵ Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
⁶ Department of Psychatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
⁷ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
⁸ Department of Prosthetic Dentistry, Gerodontology and Biomaterials, University Medicine Greifswald, Greifswald, Germany.
⁹ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.

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).