A sensitive and rapid alternative to HLA typing as a genetic screening test for abacavir hypersensitivity syndrome

被引:32
作者
Martin, Annalise M.
Krueger, Romano
Almeida, Coral Ann
Nolan, David
Phillips, Elizabeth
Mallal, Simon
机构
[1] Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia
[2] Murdoch Univ, Murdoch, WA 6150, Australia
[3] Royal Perth Hosp, Dept Haematol, Perth, WA 6000, Australia
[4] Royal Perth Hosp, Dept Clin Immunol & Biochem Genet, Perth, WA 6000, Australia
[5] St Pauls Hosp, British Columbia Ctr Excellence HIV AIDS, Vancouver, BC V6Z 1Y6, Canada
关键词
HLA-B*5701 typing; flow cytometry; abacavir hypersensitivity;
D O I
10.1097/01.fpc.0000197468.16126.cd
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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. Conclusion 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. Pharmacogenetics and Genomics 16:353-357 (c) 2006 Lippincott Williams & Wilkins.
引用
收藏
页码:353 / 357
页数:5
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