02214nas a2200277   4500000000100000008004100001100001100042700001100053700000900064700001100073700001000084700001100094700001200105700001100117700001000128700001200138700001000150700000900160700001100169700001200180700001200192700005700204245011800261520154300379022001401922       2018                            d1 aChen W1 aWang C1 aLu C1 aChen C1 aLee H1 aHung S1 aChoon S1 aYang C1 aLiu M1 aChen TJ1 aFan W1 aSu S1 aLin YY1 aChang Y1 aChung W1 aTaiwan Severe Cutaneous Adverse Reaction Consortium 00aThe function of HLA-B*13:01 involved in the pathomechanism of dapsone-induced severe cutaneous adverse reactions.3 a<p>Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions (SCAR), such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remains unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells (CTLs) involved in pathogenesis of dapsone-SCAR. We enrolled patients with DRESS and maculopapular eruption (MPE) with chronic inflammatory dermatoses, from Taiwan and Malaysia. Our results revealed that HLA-B*13:01 allele was present in 85.7% (6/7) of patients with dapsone-DRESS (OR=49.64; 95% CI=5.89-418.13; pc=2.92x10), but in only 10.8% (73/677) of general population controls in Taiwan. Granulysin level, the SCAR specific cytotoxic protein released from CTLs, was increased in both DRESS patients' plasma (36.14 ± 9.02 ng/ml, p&lt;0.05) and in vitro lymphocyte activation test (71.4%, 5 in 7 cases) compared to healthy controls. Furthermore, dapsone-specific CTLs were significantly activated when co-cultured with HLA-B*13:01-expressing antigen presenting cells in the presence of dapsone (3.9-fold increase, compared to cells with no HLA-B*13:01 expression; p&lt;0.01). This study demonstrates HLA-B*13:01 is strongly associated with dapsone-DRESS and provides a functional role of HLA-restricted immune mechanism induced by dapsone.</p>
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