The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions Wei-Ti Chen, Chuang-Wei Wang, Chun-Wei.

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The Function of HLA-B*13:01 Involved in the Pathomechanism of Dapsone-Induced Severe Cutaneous Adverse Reactions Wei-Ti Chen, Chuang-Wei Wang, Chun-Wei Lu, Chun-Bing Chen, Hua-En Lee, Shuen-Iu Hung, Siew-Eng Choon, Chih-Hsun Yang, Ming-Tsan Liu, Ting Jui Chen, Wen-Lang Fan, Shih-Chi Su, Yang Yu-Wei Lin, Ya-Ching Chang, Wen-Hung Chung Journal of Investigative Dermatology Volume 138, Issue 7, Pages 1546-1554 (July 2018) DOI: 10.1016/j.jid.2018.02.004 Copyright © 2018 The Authors Terms and Conditions

Figure 1 Cytotoxic T cells involved in the pathogenesis of dapsone DRESS. (a) Plasma granulysin expression was measured in eight patients with dapsone DRESS and nine healthy individuals. (b, c) Lymphocyte activation test (LAT) was performed in seven patients with dapsone DRESS and five healthy individuals. A positive result was defined as a 1.2-fold increase in granulysin release compared with the control individuals (solid line). Black dot indicates true positive result in granulysin-based LAT, gray dot indicates false negative result, and black triangle indicates healthy control results for comparison. (d, e) After in vitro culture assay, the populations of CD107a+ activated T cells were measured in four dapsone DRESS patients in the presence or absence of dapsone treatment. CD107a+CD3+ cells were defined as activated T cells, CD107a+CD8+ cells were defined as activated CD8+ CTLs, and CD107a+CD4+ cells were defined as activated CD4+ T cells. ∗P < 0.05 by two-tailed Student t test. Ctrl, control; DRESS, drug reaction with eosinophilia and systemic symptoms; HD, healthy donor; LAT, lymphocyte activation test; Sol., solvent. Journal of Investigative Dermatology 2018 138, 1546-1554DOI: (10.1016/j.jid.2018.02.004) Copyright © 2018 The Authors Terms and Conditions

Figure 2 HLA-B*13:01–dependent activation of dapsone-specific CTLs obtained from patients with dapsone DRESS. (a) Dapsone-specific CTLs were expanded from PBMCs of dapsone DRESS patients (n = 3) and then were in vitro cultured with C1R (non–HLA-B*13:01 carrier), C1R-t13:01 (HLA-B*13:01 carrier), C1R-t15:02 (HLA-B*15:02 carrier), or dapsone. (b) The sport results of IFN-γ release. CTLs alone treated with phytohaemagglutinin (PHA) served as a positive control. (c) Dapsone-specific CTLs were cultured in vitro with C1R-t13:01 and dapsone in the presence of isotype or anti-HLA antibodies, and (d) the sport results are shown. Values are mean ± standard error of the mean. ∗P < 0.05, ∗∗P < 0.0, by two-tailed Student t test. CTL, cytotoxic T cell; DRESS, drug reaction with eosinophilia and systemic symptoms; PBMC, peripheral blood mononuclear cell; PHA, phytohaemagglutinin. Journal of Investigative Dermatology 2018 138, 1546-1554DOI: (10.1016/j.jid.2018.02.004) Copyright © 2018 The Authors Terms and Conditions