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The function of HLA-B*13:01 involved in the pathomechanism of dapsone-induced severe cutaneous adverse reactions.

Abstract

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<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<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.

More information

Type
Journal Article
Author
Chen W
Wang C
Lu C
Chen C
Lee H
Hung S
Choon S
Yang C
Liu M
Chen TJ
Fan W
Su S
Lin YY
Chang Y
Chung W
Taiwan Severe Cutaneous Adverse Reaction Consortium