Newborn Screening for Cystic Fibrosis by Use of a Multiplex Immunoassay
Newborn Screening for Cystic Fibrosis by Use of a Multiplex Immunoassay
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DOI：
10.1373/clinchem.2009.132480
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发表时间：
2010-03-01
影响因子：
9.3
通讯作者：
Pass, Kenneth A.
中科院分区：
文献类型：
--
作者：
Lindau-Shepard, Barbara A.;Pass, Kenneth A.
背景技术背景：自成立以来，使用免疫反应性胰蛋白酶原（IRT）检测新生儿囊性纤维化（CF）的筛查一直受到高假阳性结果率（筛查阳性，诊断阴性）的困扰，尽管试图通过使用降低这一比例改变临界值和第二层DNA测试。IRT有两种亚型：IRT 1和IRT 2，其中IRT 2与胰腺疾病（包括CF）更密切相关。程序之间的测定标准化是一个持续的问题，因为目前使用的IRT测定不同地识别I或两种亚型。在这里，我们报告的发展，一个多路复用的检测两种形式的IRTsimultaneous.METHODS：使用2个不同的Luminex珠集，我们开发了每一个IRT亚型分别检测，然后将它们结合起来。使用IRT 1和IRT 2值的总和（IRT 1 + IRT 2），我们比较了结果与CF试剂盒目前正在使用。结果：在一个样本集，包括16例确诊为CF阳性，我们建立了一个截止值在>97 μ g/L的总IRT。8例经标准方法筛选为ICF突变阳性的携带者中有7例经IRT 1 + IRT 2筛选也为阳性。在标准IRT筛查阳性的32例患者中，I11例经IRT 1 + IRT 2筛查为阴性。没有这11例CF突变确定的筛选programmes.CONCLUSIONS：这些数据表明，多重方法具有特异性的2种亚型的IRT的性能可比的标准IRT方法和改进的标准化检测的2种亚型的优势。(C)2009年美国临床化学协会
BACKGROUND: Since its beginnings, newborn screening for cystic fibrosis (CF) using an assay for immunoreactive trypsinogen (IRT) has been plagued by a high rate of false-positive results (screen positive, diagnosis negative), despite attempts to reduce this rate by use of altered cutoffs and second-tier DNA testing. IRT exists as 2 isoforms: IRT1 and IRT2, with IRT2 being more closely aligned with pancreatic disease, including CF. Assay standardization between programs is a continuing problem because the IRT assays currently in use variously recognize either I or both isoforms. Here we report the development of a multiplexed assay for both forms of IRT simultaneously.METHODS: Using 2 different Luminex bead sets, we developed assays for each IRT isoform separately and then combined them. Using the sum of IRT1 and IRT2 values (IRT1+IRT2), we compared the results with a CF kit currently in use.RESULTS: In a sample set consisting of 16 cases confirmed positive for CF, we established a cutoff at >97 mu g/L total IRT. Seven of 8 carriers with I CF mutation screen-positive by the standard method were also screen-positive by IRT1+IRT2. Of 32 cases screen-positive by standard IRT, I11 were screen-negative by IRT1+IRT2. None of these 11 cases had CF mutations identified by the screening program.CONCLUSIONS: These data indicate that the multiplex method with specificity for 2 isoforms of IRT has performance comparable to that of a standard IRT method and the advantage of improved standardization by detection of the 2 isoforms. (C) 2009 American Association for Clinical Chemistry