High sensitivity of human leukocyte antigen-B*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients
High sensitivity of human leukocyte antigen-B*5701 as a marker for immunologically confirmed abacavir hypersensitivity in white and black patients
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DOI：
10.1086/529382
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发表时间：
2008-04-01
影响因子：
11.8
通讯作者：
Shaefer, Mark
中科院分区：
文献类型：
--
作者：
Saag, Michael;Balu, Rukmini;Shaefer, Mark
背景尽管人类白细胞抗原（HLA）-B*5701与阿巴卡韦（ABC）的超敏反应（HSR）高度相关，但当仅使用临床数据定义ABC HSR时，已报告了可变的敏感性。本研究评估了HLA-B*5701等位基因作为ABC HSR标记物在白色和黑人患者中检测的敏感性，并使用皮肤斑贴试验补充临床诊断。通过病历审查确定的白色和黑人患者被分类为仅基于临床结果（临床疑似ABC HSR）或基于临床结果和阳性皮肤斑贴试验结果（免疫学证实的[IC] ABC HSR）诊断为ABC HSR。对照受试者是种族匹配的受试者，其耐受ABC>= 12周而未经历ABC HSR。对患者和对照受试者进行HLA-B*5701的检测。计算了白色和黑色受试者检测HLA-B*5701作为ABC HSR标志物的敏感性、特异性和比值比。符合临床疑似HSR标准的130例白色患者中的42例（32.3%）和69例黑人患者中的5例（7.2%）有IC HSR。所有42例发生IC HSR的白色患者均为HLA-B*5701阳性（敏感性，100%;比值比，1945; 95%可信区间，110- 34，352）。在所有临床疑似HSR的白色患者中，敏感性为44%（130例患者中有57例HLA-B*5701检测阳性）;白色对照受试者的特异性为96%。5例患有IC HSR的黑人患者中有5例HLA-B*5701阳性（敏感性，100%;比值比，900; 95%置信区间，38- 21，045）。在临床疑似HSR的黑人患者中，灵敏度为14%（69例HLA-B*5701检测阳性中有10例）;在黑人对照组中的特异性为99%。虽然IC ABC HSR在黑人中并不常见，但在美国白色和黑人患者中，HLA-B*5701作为IC ABC HSR标记物的100%敏感性表明两个种族中HLA-B*5701阳性与ABC HSR风险之间的关联具有相似的意义。
Background. Although the human leukocyte antigen (HLA)-B*5701 is highly associated with a hypersensitivity reaction (HSR) to abacavir (ABC), variable sensitivities have been reported when clinical data alone have been used to define an ABC HSR. This study evaluated the sensitivity of detection of the HLA-B*5701 allele as a marker of ABC HSRs in both white and black patients, using skin patch testing to supplement clinical diagnosis.Methods. White and black patients, identified through chart review, were classified as having received a diagnosis of an ABC HSR based on clinical findings only (a clinically suspected ABC HSR) or based on clinical findings and a positive skin patch test result (an immunologically confirmed [IC] ABC HSR). Control subjects were racially matched subjects who tolerated ABC for >= 12 weeks without experiencing an ABC HSR. Patients and control subjects were tested for the presence of HLA-B*5701. Sensitivity, specificity, and odds ratios for the detection of HLA-B*5701 as a marker for an ABC HSR were calculated for white and black participants.Results. Forty-two (32.3%) of 130 white patients and 5 (7.2%) of 69 black patients who met the criteria for clinically suspected HSRs had IC HSRs. All 42 white patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 1945; 95% confidence interval, 110-34,352). Among all white patients with clinically suspected HSRs, sensitivity was 44% (57 of 130 patients tested positive for HLA-B*5701); specificity among white control subjects was 96%. Five of 5 black patients with IC HSRs were HLA-B*5701 positive (sensitivity, 100%; odds ratio, 900; 95% confidence interval, 38-21,045). Among black patients with clinically suspected HSRs, the sensitivity was 14% (10 of 69 tested positive for HLA-B*5701); specificity among black control subjects was 99%.Conclusions. Although IC ABC HSRs are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for IC ABC HSRs in both US white and black patients suggests similar implications of the association between HLA-B*5701 positivity and risk of ABC HSRs in both races.