Table_4_Toxin exposure and HLA alleles determine serum antibody binding to toxic shock syndrome toxin 1 (TSST-1) of Staphylococcus aureus.xlsx

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.

致命性中毒性休克综合征（toxic shock syndrome, TSS）通常由金黄色葡萄球菌（Staphylococcus aureus）产生的超抗原中毒性休克综合征毒素-1（toxic shock syndrome toxin-1, TSST-1）所引发。已知的高危致病因素之一为体内缺乏中和抗体。为明确抗TSST-1抗体应答的决定因素，我们纳入德国波美拉尼亚地区基于人群的健康流行病学研究（Study of Health in Pomerania, SHIP-TREND-0）的976名参与者开展分析。我们检测了抗TSST-1抗体水平，分析了携带TSST-1编码基因的金黄色葡萄球菌定植情况，并针对遗传高危因素开展了全基因组关联分析。TSST-1特异性血清IgG水平的变化跨度达4.2个对数级，且当鼻腔定植有携带TSST-1编码基因的金黄色葡萄球菌时，该抗体水平可升高12.3倍。此外，抗TSST-1抗体水平与HLA II类（HLA class II）基因位点显著相关：HLA-DRB1*03:01与HLA-DQB1*02:01与抗TSST-1抗体水平呈正相关，而HLA-DRB1*01:01及HLA-DQB1*05:01则呈负相关。综上，毒素暴露与HLA等位基因均可影响人体对TSST-1的抗体应答。