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: L Kostenko, L Kjer-Nielsen, I Nicholson, F Hudson, A Lucas, B Foley, K Chen, K Lynch, J Nguyen, A H B Wu, B D Tait, R Holdsworth, S Mallal, J Rossjohn, M Bharadwaj, J McCluskey
• Journal: Tissue antigens (Tissue Antigens) Vol. 78 Issue 1 Pg. 11-20 (Jul 2011) ISSN: 1399-0039 [Electronic] England
• PMID: 21501118 (Publication Type: Evaluation Study, Journal Article)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Antibodies, Monoclonal
• HLA-B Antigens
• HLA-B57 antigen
• HLA-B58

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Monoclonal (biosynthesis, isolation & purification, metabolism, pharmacology)
• Antibody Formation
• Antibody Specificity
• Cells, Cultured
• Drug Hypersensitivity (genetics, immunology, prevention & control)
• Enzyme-Linked Immunosorbent Assay
• HLA-B Antigens (analysis, genetics, immunology)
• Histocompatibility Testing (methods)
• Humans
• Mass Screening (methods)
• Mice
• Mice, Inbred BALB C
• Models, Molecular
• Molecular Sequence Data
• Time Factors