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TAP2 Drives HLA-B∗13:01‒Linked Dapsone Hypersensitivity Syndrome Tolerance and Reactivity.
Sun, Lele; Wang, Zhenzhen; Liu, Tingting; Zhao, Qing; Yu, Gongqi; Sun, Yonghu; Xue, Xiaotong; You, Jiabao; Yue, Zhenhua; Mi, Zihao; Liu, Hong; Zhang, Furen.
Afiliación
  • Sun L; Shandong 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.
  • Wang Z; Shandong 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.
  • Liu T; Shandong 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.
  • Zhao Q; Shandong 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.
  • Yu G; Shandong 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.
  • Sun Y; Shandong 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.
  • Xue X; Shandong 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.
  • You J; Shandong 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.
  • Yue Z; Shandong 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.
  • Mi Z; Shandong 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.
  • Liu H; Shandong 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.
  • Zhang F; Shandong 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. Electronic address: zhangfuren@hotmail.com.
J Invest Dermatol ; 143(5): 722-730.e1, 2023 05.
Article en En | MEDLINE | ID: mdl-37306379
Dapsone hypersensitivity syndrome (DHS) is restricted to HLA-B∗13:01. However, the positive predictive value for HLA-B∗13:01 is only 7.8%. To explore the potential coexisting factors involved in the occurrence of DHS, we carried out a GWAS and a genome-wide DNA methylation profile analysis comparing patients with DHS with dapsone-tolerant control subjects (all carrying HLA-B∗13:01). No non-HLA SNPs associated with DHS were identified at the genome-wide level. However, the pathway of antigen processing and presentation was enriched in patients with DHS, and the gene TAP2 was identified. Expression of TAP2 and its molecular chaperone, TAP1, were validated by quantitative PCR, and in vitro functional experiments were performed. The results showed that patients with DHS have higher mRNA levels of TAP1 and TAP2 and an enhanced capacity for antigen-presenting cells activating dapsone-specific T cells compared with dapsone-tolerant controls. Activation of dapsone-specific T cells was inhibited when TAP function of antigen-presenting cells was impaired. This study shows that epigenetic regulation of TAP1 and TAP2 affects the function of antigen-presenting cells and is a critical factor that mediates the development of DHS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Hipersensibilidad a Medicamentos / Hipersensibilidad Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome de Hipersensibilidad a Medicamentos / Hipersensibilidad Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos