Development of population-based newborn screening for severe combined immunodeficiency
Development of population-based newborn screening for severe combined immunodeficiency
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DOI：
10.1016/j.jaci.2004.10.012
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发表时间：
2005-02-01
影响因子：
14.2
通讯作者：
Puck, JM
中科院分区：
文献类型：
--
作者：
Chan, K;Puck, JM
背景：重症联合免疫缺陷（SCID）是一种可治疗的遗传性细胞免疫和体液免疫缺乏症，由多个不同基因的多种突变引起，若不进行免疫重建，婴儿期就会死亡。目前没有针对SCID的群体筛查，但早期诊断会改善预后。
目的：由于所有SCID患者产生的T细胞很少或没有，我们探究新形成的T细胞中的DNA游离基因——T细胞受体切除环（TRECs）的缺失是否能识别SCID，而不论其基因型如何。
方法：从干血斑中分离的DNA通过实时聚合酶链反应（PCR）来定量TRECs。对β -肌动蛋白基因的一个片段进行对照PCR。在对成人和脐带血对照受试者进行初步研究后，将SCID患者的血液点样到滤纸上进行检测，随后对马里兰州新生儿筛查项目中的实际血斑进行筛查。最后，在2名婴儿被诊断为SCID后，获取并检测他们的新生儿血斑。
结果：与新生儿筛查项目的滤纸（在两个3毫米的打孔样本中平均有1020个TRECs）相比，23名SCID婴儿的样本中TRECs少于30个。从州实验室获取了其中一名婴儿以及另一名先前死于SCID的婴儿的新生儿筛查滤纸；尽管两个样本都可检测到β -肌动蛋白DNA，但都没有TRECs。
结论：TRECs是一种稳定的分析物，能够识别新生儿干血斑中的T细胞淋巴细胞减少症，从而使SCID婴儿能够接受早期的挽救生命的治疗。
Background: Severe combined immunodeficiency (SCID) is a treatable, inherited lack of cellular and Immoral immunity caused by diverse mutations in several different genes and leading to death in infancy unless immune reconstitution is provided. Currently no population screening exists for SCID, but early diagnosis would improve outcome.Objective: Because all patients with SCID make few or no T cells, we asked whether the absence of T-cell receptor excision circles (TRECs), DNA episomes in newly formed T cells, could identify SCID regardless of genotype.Methods: DNA isolated from dried blood spots was assayed by real-time PCR to quantitate TRECs. Control PCR was performed on a segment of the P-actin gene. After pilot studies with adult and cord blood control subjects, blood from SCID patients was spotted onto filters and tested, followed by screening of actual blood spots from the Maryland Newborn Screening Program. Finally, newborn blood spots were recovered and tested from 2 infants after their diagnosis of SCID.Results: In contrast to filters from the newborn screening program, which had a mean of 1020 TRECs in two 3-mm punches, samples from 23 infants with SCID had < 30 TRECs. The newborn screening filter was retrieved from a state laboratory for one of these infants plus another infant who had died of SCID previously; although both samples had detectable R-actin DNA, neither had TRECs.Conclusion: TRECs are a stable analyte that can identify T-cell lymphopenia in newborn dried blood spots so that infants with SCID can receive early, life-saving treatment.