Research Information System University of Greifswald

Weiss S*¹, Holtfreter S², Meyer T¹, Schmiedeke F², Cammann C³, Dörr M⁴, Felix S, Grabe H⁵, Homuth G¹, Kohler C³, Mahncke C², Michalik S¹, Nauck M⁶, Friedrich N⁶, Samietz S⁷, Völzke H⁸, Völker U¹, Bröker B²

1 - Interfakultäres Institut für Genetik und Funktionelle Genomforschung / Abt. Funktionelle Genomforschung

2 - Institut für Immunologie und Transfusionsmedizin / Abt. Medizinische Immunologie

3 - Friedrich Loeffler Institut für Medizinische Mikrobiologie

4 - Zentrum für Innere Medizin / Klinik für Innere Medizin B

5 - Klinik und Poliklinik für Psychiatrie und Psychotherapie

6 - Institut für Klinische Chemie und Laboratoriumsmedizin

7 - Zentrum für Zahn-, Mund- und Kieferheilkunde / Poliklinik für Zahnärztliche Prothetik, Alterszahnheilkunde und Medizinische Werkstoffkunde

8 - Institut für Community Medicine / Abt. SHIP KEF

Life-threatening toxic shock syndrome is often caused by the superantigen toxic shock syndrome toxin-1 (TSST-1) produced by . 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 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 . 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.