Human leukocyte antigens and drug hypersensitivity.

Abstract

PURPOSE OF REVIEW:

The present article reviews the recent literature on the identification of human leukocyte antigen (HLA) alleles as major susceptible genes for drug hypersensitivity and discusses the clinical implications.

RECENT FINDINGS:

Several recent studies have reported strong genetic associations between HLA alleles and susceptibility to drug hypersensitivity. The genetic associations can be drug specific, such as HLA-B*1502 being associated with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN), HLA-B*5701 with abacavir hypersensitivity and HLA-B*5801 with allopurinol-induced severe cutaneous adverse reactions. A genetic association can also be phenotype-specific, as B*1502 is associated solely with carbamazepine-SJS/TEN, and not with either maculopapular eruption or hypersensitivity syndrome. Furthermore, a genetic association can also be ethnicity specific; carbamazepine-SJS/TEN associated with B*1502 is seen in south-east Asians but not in whites, which may be explained by the different allele frequencies.

SUMMARY:

The strong genetic association suggests a direct involvement of HLA in the pathogenesis of drug hypersensitivity when the HLA molecule presents an antigenic drug for T cell activation. The high sensitivity/specificity of some markers provides a plausible basis for developing tests to identify individuals at risk for drug hypersensitivity. Application of HLA-B*1502 genotyping as a screening tool before prescribing carbamazepine could be a valuable tool in preventing carbamazepine-induced SJS/TEN in south-east Asian countries.

• Authors: Wen-Hung Chung, Shuen-Iu Hung, Yuan-Tsong Chen
• Journal: Current opinion in allergy and clinical immunology (Curr Opin Allergy Clin Immunol) Vol. 7 Issue 4 Pg. 317-23 (Aug 2007) ISSN: 1528-4050 [Print] United States
• PMID: 17620823 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Dideoxynucleosides
• HLA Antigens
• HLA-B Antigens
• Carbamazepine
• Allopurinol
• abacavir

Topics

• Allopurinol (adverse effects)
• Carbamazepine (adverse effects)
• Dideoxynucleosides (adverse effects)
• Drug Eruptions (genetics, immunology)
• Drug Hypersensitivity (genetics, immunology)
• Genetic Predisposition to Disease
• HLA Antigens (genetics)
• HLA-B Antigens (genetics)
• Humans
• Pharmacogenetics
• Stevens-Johnson Syndrome (genetics, immunology)