title: Rapid screening for the detection of HLA-B57 and HLA-B58 in prevention of drug hypersensitivity.
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.
authors.affiliation: Department of Microbiology and Immunology, The University of Melbourne, Parkville, Victoria, Australia. lyudmila@unimelb.edu.au
authors.forename: L
authors.initials: L
authors.lastname: Kostenko
authors.forename: L
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: I
authors.initials: I
authors.lastname: Nicholson
authors.forename: F
authors.initials: F
authors.lastname: Hudson
authors.forename: A
authors.initials: A
authors.lastname: Lucas
authors.forename: B
authors.initials: B
authors.lastname: Foley
authors.forename: K
authors.initials: K
authors.lastname: Chen
authors.forename: K
authors.initials: K
authors.lastname: Lynch
authors.forename: J
authors.initials: J
authors.lastname: Nguyen
authors.forename: A H B
authors.initials: AH
authors.lastname: Wu
authors.forename: B D
authors.initials: BD
authors.lastname: Tait
authors.forename: R
authors.initials: R
authors.lastname: Holdsworth
authors.forename: S
authors.initials: S
authors.lastname: Mallal
authors.forename: J
authors.initials: J
authors.lastname: Rossjohn
authors.forename: M
authors.initials: M
authors.lastname: Bharadwaj
authors.forename: J
authors.initials: J
authors.lastname: McCluskey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D000917:Antibody Formation; D000918:Antibody Specificity; D002478:Cells, Cultured; D004342:Drug Hypersensitivity / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay; D015235:HLA-B Antigens / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods; D006801:Humans; D008403:Mass Screening / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; C562005:HLA-B58