Martin Annalise M, Krueger Romano, Almeida Coral Ann, Nolan David, Phillips Elizabeth, Mallal Simon
Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Western Australia 6000, Australia.
Pharmacogenet Genomics. 2006 May;16(5):353-7. doi: 10.1097/01.fpc.0000197468.16126.cd.
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-B5701, indicating that exclusion of HLA-B5701 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.
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.
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.
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.
阿巴卡韦超敏反应（ABC HSR）是一种潜在的危及生命的不良反应，约8%开始使用这种抗逆转录病毒药物的患者会出现该反应。独立研究小组已表明ABC HSR与HLA - B5701之间存在很强的预测关联，这表明将HLA - B5701阳性个体排除在阿巴卡韦治疗之外可在很大程度上预防ABC HSR。然而，人类白细胞抗原（HLA）分型的有限可及性和相对较高的成本成为了在阿巴卡韦处方中广泛实施这种药物遗传学方法的障碍。为便于进行常规筛查，我们开发了一种使用市售B17单克隆抗体进行HLA - B57表型分析的快速流式细胞术方法。
采用双色B17特异性免疫荧光测定法，对84例人类免疫缺陷病毒（HIV）患者的全血样本在CD45淋巴细胞群体中进行标准流式细胞术检测。
检测的所有8例HLA - B57个体均呈阳性，而HLA - B57/58阴性个体（n = 74）在该流式细胞术检测中呈阴性。2例非HLA - B57个体表现出弱交叉反应。
在我们主要为白种人的人群中，B17/CD45双重染色足以识别携带B17细胞表面抗原的个体。这种利用HIV实验室广泛可用的流式细胞术方法的途径，因此在阿巴卡韦处方前提供了一种灵敏、快速且经济高效的筛查检测方法。通过该检测进行风险分层后，预计在筛查人群中<10%的个体需要使用分子HLA分型方法鉴定HLA - B*5701。
