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

Tissue Antigens. 2011 Jul;78(1):11-20. doi: 10.1111/j.1399-0039.2011.01649.x. Epub 2011 Apr 19.

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 types

  • Evaluation Study

MeSH terms

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

Substances

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