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

Lyudmila Kostenko, Lars Kjer-Nielsen, I Nicholson, F Hudson, A Lucas, B Foley, K Chen, K Lynch, J Nguyen, A Wu, Brian Tait, Rhonda Holdsworth, Simon Mallal, Jamie Rossjohn, Mandvi Bharadwaj, James McCluskey

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39 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)11 - 20
Number of pages10
JournalTissue Antigens
Volume78
Issue number1
DOIs
Publication statusPublished - 2011

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