HLA and drug reactions
Phillips, E.J. and Mallal, S.A. (2010) HLA and drug reactions. In: Mehra, N.K., Kaur, G., McCluskey, J., Christiansen, F.T. and Claas, F.H.J., (eds.) The HLA Complex in Biology and Medicine: A Resource Book. Jaypee Brothers Medical Publishers (P) Ltd, New Delhi, India, pp. 332-349.
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Adverse drug reactions represent a significant burden from a hospital, healthcare and societal perspective comprising the 4th to 6th most common cause of death in some series. Clinically, adverse drug reactions have been classified according to those that are predictable and dose-dependent on the basis of their pharmalogical actions ("Type A") versus those that are believed to be immunogenetically mediated and not predictable based on traditional clinical and pharmalogical properties of the drug ("Type B") (Table 20.1). A major breakthrough has been the association between HLA class I and II alleles and Type B adverse drug reactions. Examples include the striking association between HLA-B*5701 and abacavir hypersensitivity syndrome (ABC HSR), HLA-B*1502 and Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN) associated with carbamazepine, and HLA-B*5801 and drug-induced hypersensitivity syndrome (DIHS) and SJS/TEN associated with allopurinol. These associations have been facilitated by the introduction of molecular methods improving the accuracy and resolution of HLA typing and improved phenotyping of specific drug toxicities. Furthermore, the discovery of associations between specific HLA and these drug toxicities such DIHS and SJS/TEN have fuelled our understanding of the immunopathogenesis of these syndromes. The associations between HLA and drug toxicity are hence important from both a clinical and scientific point of view. Drugs may be viewed as an experiment of man acting as a probe to provoke potentially vigorous and life threatening HLA-restricted immune responses. From a clinical standpoint the association between HLA drug toxicity represents an impotant opportunity to increase drug safety and prevent the traditionally unpredictable Type B reactions by excluding high-risk patients from the drug in question. The widespread uptake of HLA-based pharmacogenetics from discovery to clinical implementation.
|Publication Type:||Book Chapter|
|Murdoch Affiliation:||Institute for Immunology and Infectious Diseases|
|Publisher:||Jaypee Brothers Medical Publishers (P) Ltd|
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