Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

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
*Subscription may be required

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.

Item 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
Item Control Page Item Control Page