Investigation of immunogenetic risk factors for carbamazepine-induced hypersensitivity reactions


Lichtenfels, Maike (2014) Investigation of immunogenetic risk factors for carbamazepine-induced hypersensitivity reactions. PhD thesis, University of Liverpool.

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Abstract

T-cell mediated hypersensitivity reactions (HSRs) to carbamazepine (CBZ), a commonly used anti-epileptic drug, occur only in a small proportion of patients, but can often be severe in nature. As the underlying pathomechanisms are not fully understood, it has proven difficult to predict who may be at risk of developing CBZ-induced HSRs. Recently, specific human leukocyte antigen (HLA) alleles have been identified as susceptibility factors for CBZ hypersensitivity in diverse populations, indicating that HLA molecules may be functionally involved in CBZ-induced T-cell activation. HLA-A*31:01 represents the latest example and has been implicated in CBZ-induced HSRs in Caucasian patients. Thus, the aim of this work was to explore the molecular interactions of CBZ with HLA-A*31:01 and drug-specific T-cells. The HLA restriction pattern of CBZ-reactive T-cells from a patient expressing HLA-A*31:01 was investigated. It was shown that CD8+ T-cells were activated in a HLA-A*31:01 dependent way. Further, HLA-DRB1*04:04 was found to be responsible for the stimulation of CD4+ T-cells, suggesting a common HLA haplotype may be involved in mediating T-cell responses to CBZ in Europeans. Next, in vitro priming of drug-naïve ... (continues)

Item Type: Thesis (PhD)
Additional Information: Date: 2014-03 (completed)
Divisions: Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User: Symplectic Admin
Date Deposited: 09 Mar 2015 14:52
Last Modified: 08 Feb 2025 00:25
DOI: 10.17638/00019333
Supervisors:
URI: https://livrepository.liverpool.ac.uk/id/eprint/19333
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