PDF(Pubmed)
Abstract：
Severe combined immunodeficiency (SCID) is a group of inborn errors of immunity (IEI) characterized by severe T- and/or B-lymphopenia. At birth, there are usually no clinical signs of the disease, but in the first year of life, often in the first months the disease manifests with severe infections. Timely diagnosis and treatment play a crucial role in patient survival. In Ukraine, the expansion of hemostatic stem cell transplantation and the development of a registry of bone marrow donors in the last few years have created opportunities for early correction of IEI and improving the quality and life expectancy of children with SCID. For the first time in Ukraine, we initiated a pilot study on newborn screening for severe combined immunodeficiency and T-cell lymphopenia by determining T cell receptor excision circles (TRECs) and kappa-deleting recombination excision circles (KRECs). The analysis of TREC and KREC was performed by real-time polymerase chain reaction (RT-PCR) followed by analysis of melting curves in neonatal dry blood spots (DBS). The DBS samples were collected between May 2020 and January 2022. In total, 10,350 newborns were screened. Sixty-five blood DNA samples were used for control: 25 from patients with ataxia-telangiectasia, 37 - from patients with Nijmegen breakage syndrome, 1 - with X-linked agammaglobulinemia, 2 - with SCID (JAK3 deficiency and DCLRE1C deficiency). Retest from the first DBS was provided in 5.8% of patients. New sample test was needed in 73 (0.7%) of newborns. Referral to confirm or rule out the diagnosis was used in 3 cases, including one urgent abnormal value. CID (TlowB+NK+) was confirmed in a patient with the urgent abnormal value. The results of a pilot study in Ukraine are compared to other studies (the referral rate 1: 3,450). Approbation of the method on DNA samples of children with ataxia-telangiectasia and Nijmegen syndrome showed a high sensitivity of TRECs (a total of 95.2% with cut-off 2000 copies per 106 cells) for the detection of these diseases. Thus, the tested method has shown its effectiveness for the detection of T- and B-lymphopenia and can be used for implementation of newborn screening for SCID in Ukraine.
摘要：
严重联合免疫缺陷（SCID）是一组先天性免疫错误（IEI），其特征是严重的T和/或B淋巴细胞减少。出生时,通常没有这种疾病的临床症状，但是在生命的第一年，通常在最初的几个月，这种疾病表现为严重的感染。及时的诊断和治疗对患者的生存起着至关重要的作用。在乌克兰,在过去几年中,止血干细胞移植的扩大和骨髓捐献者登记的发展为早期纠正IEI和提高SCID患儿的质量和预期寿命创造了机会.第一次在乌克兰我们通过测定T细胞受体切除环(TRECs)和κ缺失重组切除环(KRECs),启动了一项针对重度联合免疫缺陷和T细胞淋巴细胞减少症的新生儿筛查的初步研究.通过实时聚合酶链反应（RT-PCR）进行TREC和KREC的分析，然后分析新生儿干血点（DBS）的熔解曲线。DBS样本是在2020年5月至2022年1月之间收集的。总的来说,筛查了10,350名新生儿。65个血液DNA样本用于对照：25个来自共济失调-毛细血管扩张症患者，37-来自奈梅亨破损综合征患者，1-X连锁无丙种球蛋白血症，2-SCID（JAK3缺乏症和DCLRE1C缺乏症）。5.8%的患者从第一次DBS开始进行复检。73例(0.7%)新生儿需要进行新的样本检测。3例采用转诊确认或排除诊断,包括一个紧急异常值。CID(TlowB+NK+)在有紧急异常值的患者中得到证实。将乌克兰的一项试点研究的结果与其他研究进行比较（转诊率1：3,450）。对共济失调毛细血管扩张症和奈梅亨综合征儿童的DNA样本的方法的认可显示，TREC的敏感性很高（总计95.2％，每106个细胞截止2000个拷贝），用于检测这些疾病。因此，该试验方法已显示其检测T-和B-淋巴细胞减少的有效性,可用于在乌克兰实施SCID的新生儿筛查.
