TAP2驱动HLA-B13:01 - 相关的达普森过敏综合征耐受性和反应性
Lele Sun1, Zhenzhen Wang1, Tingting Liu1
1Shandong Provincial Hospital for Skin Diseases and Shandong Provincial Institute of Dermatology and Venereology, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
The Journal of investigative dermatology
|June 12, 2023
概括
达普森过敏综合征 (DHS) 不仅涉及HLA-B*13:01.01. TAP1和TAP2基因的表观遗传变化影响抗原呈现,增加了这种HLA类型患者的DHS风险.
科学领域:
- 药物基因组学 药物基因组学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 达普森过敏综合征 (DHS) 与HLA-B*13:01等位基因密切相关.
- 然而,HLA-B*13:01的低正预测值表明其他遗传或表观遗传因素有助于DHS.
研究的目的:
- 调查影响HLA-B*13:01阳性个体中DHS发生的共存遗传和表观遗传因素.
- 阐明抗原处理和呈现途径在DHS病原发生中的作用.
主要方法:
- 全基因组关联研究 (GWAS) 和全基因组DNA甲基化概况在DHS患者和达普森耐受性对照组 (所有HLA-B*13:01阳性).
- 定量PCR验证TAP1和TAP2mRNA的表达.
- 实验室功能测试评估了达特异性T细胞的抗原呈现细胞激活和TAP功能受损的影响.
主要成果:
- 没有全基因组显著的非HLA单核酸多态 (SNP) 与DHS相关.
- 抗原处理和呈现途径在DHS患者中得到了丰富,其中TAP2被确定为关键基因.
- 患有DHS的患者表现出更高的TAP1和TAP2mRNA水平,以及抗原呈现细胞对达特异性T细胞的增强激活,这被TAP功能受损所废除.
结论:
- TAP1和TAP2的表观遗传调节会影响抗原呈现细胞的功能.
- 这些表观遗传修饰是达普森过敏综合征发展的关键调解者,超出了初级HLA关联.
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