Abstract
Background Hypersensitivity reactions to carbamazepine (CBZ) have been shown to be strongly associated with specific human leukocyte antigen (HLA) alleles, with carriers of the HLA alleles presenting an increased risk of developing hypersensitivity. HLA-B*15:02 was detected in almost all cases of CBZ-induced Stevens-Johnson syndrome (SJS) in patients of Han Chinese or South-East Asian ancestry, and its functional role in CBZ-induced SJS has been well characterised. HLA-A*3101 is associated with all clinical phenotypes of CBZ-induced hypersensitivity in Caucasian and Japanese patients. However, functional studies investigating the role of HLA-A*31:01 in CBZ-specific T-cell responses have not been performed. Furthermore, CBZ-specific T-cells of CD4+ and CD8+ phenotype are readily detectable in Caucasian patients, which is in stark contrast to the dominant CD8+ T-cell response in Han Chinese. In this study we therefore investigated the HLA restriction of CBZ-reactive T-cells from a HLA-A*31:01 positive CBZ hypersensitive patient, focusing on both the CD4+ and CD8+ cells.
Highlights
Hypersensitivity reactions to carbamazepine (CBZ) have been shown to be strongly associated with specific human leukocyte antigen (HLA) alleles, with carriers of the HLA alleles presenting an increased risk of developing hypersensitivity
Activation of CD8+ T-cell clones (TCC) could be blocked by an antiHLA class I antibody, and when an anti-HLA A30/
CBZ reactivity of CD4+ TCC was restricted by HLA class II, predominantly HLA-DR and HLA-DP
Summary
Hypersensitivity reactions to carbamazepine (CBZ) have been shown to be strongly associated with specific human leukocyte antigen (HLA) alleles, with carriers of the HLA alleles presenting an increased risk of developing hypersensitivity. From 6th Drug Hypersensitivity Meeting (DHM 6) Bern, Switzerland. Background Hypersensitivity reactions to carbamazepine (CBZ) have been shown to be strongly associated with specific human leukocyte antigen (HLA) alleles, with carriers of the HLA alleles presenting an increased risk of developing hypersensitivity. HLA-B*15:02 was detected in almost all cases of CBZ-induced Stevens-Johnson syndrome (SJS) in patients of Han Chinese or South-East Asian ancestry, and its functional role in CBZ-induced SJS has been well characterised.
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