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Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity

Kostenko, L., Kjer-Nielsen, L., Nicholson, I., Hudson, F., Lucas, A., Foley, B., Chen, K., Lynch, K., Nguyen, J., Wu, A.H.B., Tait, B.D., Holdsworth, R., Mallal, S., Rossjohn, J., Bharadwaj, M. and McCluskey, J. (2011) Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity. Tissue Antigens, 78 (1). pp. 11-20.

Link to Published Version: http://dx.doi.org/10.1111/j.1399-0039.2011.01649.x
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Abstract

HLA-B57 and HLA-B58 are major histocompatibility class (MHC)-I allotypes that are potentially predictive of important clinical immune phenotypes. HLA-B*5701 is strongly associated with hypersensitivity to the HIV drug abacavir, liver toxicity from the antibiotic flucloxacillin and is a marker for slow progression of HIV AIDS. HLA-B*5801 is associated with hypersensitivity to allopurinol used to treat hyperuricaemia and recurrent gout. Here we describe a monoclonal antibody (mAb) specific for HLA-B57 and HLA-B58 that provides an inexpensive and sensitive screen for these MHC-I allotypes. The usefulness of HLA-B57 screening for prediction of abacavir hypersensitivity was shown in three independent laboratories, including confirmation of the mAb sensitivity and specificity in a cohort of patients enrolled in the PREDICT-1 trial. Our data show that patients who test negative by mAb screening comprise 90%-95% of all individuals in most human populations and require no further human leukocyte antigen (HLA) typing. Patients who test positive by mAb screening should proceed to high-resolution typing to ascertain the presence of HLA-B*5701 or HLA-B*5801. Hence, mAb screening provides a low-cost alternative to high-resolution typing of all patients and lends itself to point-of-care diagnostics and rapid ascertainment of low-risk patients who can begin immediate therapy with abacavir, flucloxacillin or allopurinol.

Publication Type: Journal Article
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Publisher: Blackwell Publishing Inc.
Copyright: © 2011 John Wiley & Sons A/S
URI: http://researchrepository.murdoch.edu.au/id/eprint/4618
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