课题组前期与新加坡国立基因组研究所合作将氨苯砜所致药物超敏反应综合症（DHS）的风险位点定位于HLA-B*13:01，研究结果发表在《New England J of Medicine》杂志上，但氨苯砜如何与该位点相互作用诱导DHS发生的机理尚不清楚。且HLA-B*13:01的阳性预测值仅7.8%，提示在药物、HLA分子外还有其他协同因素参与疾病的发生，具体机制有待进一步证实。因此合作双方下一步拟通过T淋巴细胞培养、抗原肽谱分析、晶体纯化、折叠等技术构建氨苯砜HLA-B*13:01-多肽复合物三维晶体结构模型，为DHS的发生机制提供免疫和结构生物学证据；后续分组检测HHV6病毒感染、角质形成细胞凋亡情况以阐释氨苯砜所致DHS的分子生物学机制，为基因研究向临床医学转化、推进个体化医疗、实现氨苯砜所致DHS的一级预防奠定基础。

We have identified HLA-B*13:01 as the main trigger factor to the development of dapsone hypersensitivity syndrome in collaboration with the research group leading by Professor Liu Jianjun in Genome Institute of Singapore, which was published in New England Journal of Medicine.(Funded by the National Natural Science Foundation of China). However, the underlying pathogenesis remains unclear. At the meantime,the positive predictive value of HLA-B*13:01 was only 7.8%, indicating not only the interaction between drugs and HLA molecules, but also other aspects also involved in the development of diseases, which has yet to be investigated. Here, we plan to construct the dapsone HLA-B * 13:01-peptide complex three-dimensional crystal structure model by T-cell assays、Peptide repertoire analyse and HLA-B*13:01 expression et al to provide immunologic and biological evidence for the pathogenesis; And the dapsone-induced molecular mechanisms of DHS will be clarified by further follow-up by HHV-6 virus detection, sFasL keratinocyte apoptosis and expression of cell detection, which will benefit the understanding of the pathogenesis basis on drug induced hypersensitivity syndrome.