Human leukocyte antigens and drug hypersensitivity.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Chung
Wen-Hung
WH
Molecular Medicine Program of Taiwan International Graduate Program, Institute of Biomedical Sciences, Academia Sinica and School of Life Sciences, National Yang-Ming University, Taipei, Taiwan.
Hung
Shuen-Iu
SI
Chen
Yuan-Tsong
YT
D000493:Allopurinol / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D015224:Dideoxynucleosides / Q000009:adverse effects; D003875:Drug Eruptions / Q000235:genetics / Q000276:immunology; D004342:Drug Hypersensitivity / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics; D013262:Stevens-Johnson Syndrome / Q000235:genetics / Q000276:immunology; D000099227:Abacavir
D000493:Allopurinol; D002220:Carbamazepine; D015224:Dideoxynucleosides; D006680:HLA Antigens; D015235:HLA-B Antigens; D000099227:Abacavir