Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA

Yun, J; Adam, J; Yerly, D; Pichler, W J (2012). Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA. Allergy, 67(11), pp. 1338-46. Oxford: Wiley-Blackwell 10.1111/all.12008

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Recent publications have shown that certain human leukocyte antigen (HLA) alleles are strongly associated with hypersensitivity to particular drugs. As HLA molecules are a critical element in T-cell stimulation, it is no surprise that particular HLA alleles have a direct functional role in the pathogenesis of drug hypersensitivity. In this context, a direct interaction of the relevant drug with HLA molecules as described by the p-i concept appears to be more relevant than presentation of hapten-modified peptides. In some HLA-associated drug hypersensitivity reactions, the presence of a risk allele is a necessary but incomplete factor for disease development. In carbamazepine and HLA-B*15:02, certain T-cell receptor (TCR) repertoires are required for immune activation. This additional requirement may be one of the 'missing links' in explaining why most individuals carrying this allele can tolerate the drug. In contrast, abacavir generates polyclonal T-cell response by interacting specifically with HLA-B*57:01 molecules. T cell stimulation may be due to presentation of abacavir or of altered peptides. While the presence of HLA-B*58:01 allele substantially increases the risk of allopurinol hypersensitivity, it is not an absolute requirement, suggesting that other factors also play an important role. In summary, drug hypersensitivity is the end result of a drug interaction with certain HLA molecules and TCRs, the sum of which determines whether the ensuing immune response is going to be harmful or not.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology

UniBE Contributor:

Yerly, Daniel and Pichler, Werner Joseph

ISSN:

0105-4538

Publisher:

Wiley-Blackwell

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:40

Last Modified:

06 Dec 2013 13:38

Publisher DOI:

10.1111/all.12008

PubMed ID:

22943588

Web of Science ID:

000309715300003

URI:

https://boris.unibe.ch/id/eprint/16258 (FactScience: 223859)

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