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Human leukocyte antigens and drug hypersensitivity
Wen-Hung Chung1, Shuen-Iu Hung, Yuan-Tsong Chen
1Molecular Medicine Program of Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica and School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Current Opinion in Allergy and Clinical Immunology
|July 11, 2007
Summary
Human leukocyte antigen (HLA) alleles are key genetic factors in drug hypersensitivity. Specific HLA types predict severe reactions to drugs like carbamazepine, enabling risk assessment and prevention strategies.
Area of Science:
- Immunogenetics
- Pharmacogenomics
- Clinical Immunology
Background:
- Drug hypersensitivity reactions (DHRs) pose significant clinical challenges.
- Identifying genetic predispositions is crucial for personalized medicine.
Purpose of the Study:
- To review recent literature on human leukocyte antigen (HLA) alleles as susceptibility genes for DHRs.
- To discuss the clinical implications of these genetic associations.
Main Methods:
- Literature review of recent studies.
- Analysis of genetic associations between HLA alleles and DHRs.
- Examination of drug-specific, phenotype-specific, and ethnicity-specific associations.
Main Results:
- Strong genetic associations identified between specific HLA alleles and DHRs.
- Examples include HLA-B*1502 with carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), HLA-B*5701 with abacavir hypersensitivity, and HLA-B*5801 with allopurinol-induced severe cutaneous adverse reactions.
- Associations can be drug, phenotype, and ethnicity specific, with HLA-B*1502 and carbamazepine-SJS/TEN observed in South-East Asians but not Caucasians.
Conclusions:
- HLA alleles play a direct role in DHR pathogenesis via T cell activation.
- High sensitivity/specificity markers can identify individuals at risk.
- HLA-B*1502 genotyping before carbamazepine prescription can prevent SJS/TEN in South-East Asian populations.
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