A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome.
BACKGROUND
Abacavir hypersensitivity reaction (ABC HSR) is a potentially life-threatening adverse reaction that affects approximately 8% of patients that initiate this antiretroviral drug. Independent groups have shown a strong predictive association between ABC HSR and HLA-B*5701, indicating that exclusion of HLA-B*5701 positive individuals from abacavir treatment would largely prevent ABC HSR. However, the limited availability and relatively high cost of human leukocyte antigen (HLA) typing represent barriers to the widespread implementation of this pharmacogenetic approach to abacavir prescribing. To facilitate routine screening, we have developed a rapid flow cytometry method for HLA-B57 phenotyping using commercially available B17 monoclonal antibodies.


METHODS
Whole blood samples from 84 human immunodeficiency virus (HIV) patients were examined by standard flow cytometry methods, using a two-colour B17-specific immunofluorescence assay in the CD45 lymphocyte population.


RESULTS
All eight HLA-B57 individuals examined tested positive, while HLA-B57/58 negative individuals (n=74) tested negative for this flow cytometry test. Two non-HLA-B57 individuals showed weak cross-reactivity.


CONCLUSIONS
In our predominantly Caucasian population, B17/CD45 dual staining was sufficient to identify individuals carrying B17 cell surface antigens. This approach, utilizing flow cytometry methods that are widely available in HIV laboratories, therefore offers a sensitive, rapid and cost-effective screening assay prior to abacavir prescription. Following risk stratification with this assay, it would be anticipated that identification of HLA-B*5701 using molecular HLA typing methods would be required in <10% of the screened population.
Martin
Annalise M
AM
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia 6000, Australia.
Krueger
Romano
R
Almeida
Coral Ann
CA
Nolan
David
D
Phillips
Elizabeth
E
Mallal
Simon
S
D000483:Alleles; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D004342:Drug Hypersensitivity / Q000235:genetics / Q000517:prevention & control*; D005434:Flow Cytometry; D005820:Genetic Testing; D006679:HIV Seropositivity; D015235:HLA-B Antigens / Q000235:genetics; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D012680:Sensitivity and Specificity; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C103707:HLA-B57 antigen