First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain)
First Universal Newborn Screening Program for Severe Combined Immunodeficiency in Europe. Two-Years' Experience in Catalonia (Spain)
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DOI：
10.3389/fimmu.2019.02406
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发表时间：
2019-10-22
影响因子：
7.3
通讯作者：
Soler-Palacin, Pere
中科院分区：
文献类型：
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作者：
Argudo-Ramirez, Ana;Martin-Nalda, Andrea;Soler-Palacin, Pere
严重联合免疫缺陷 (SCID) 是最严重的 T 细胞免疫缺陷形式，可以通过量化干血斑 (DBS) 样本中的 T 细胞受体切除环 (TREC) 在出生时进行筛查。及早发现这种情况可以加快制定适当的治疗方法并延长患者的预期寿命。加泰罗尼亚于 2017 年 1 月开始开展新生儿 SCID 筛查，这是西班牙和欧洲第一个普遍纳入此项检测的地区。此处评估前 2 年经验中获得的结果。 2017 年 1 月至 2018 年 12 月期间出生的所有婴儿均接受了筛查。使用 PerkinElmer（芬兰图尔库）的 Enlite 新生儿 TREC 试剂盒在 DBS（直径 1.5mm）中进行 TREC 定量。 2018年，检测算法中的复检截止点在第一年的经验基础上进行了更新，由34拷贝/μL改为24拷贝/μL，复检率从3.34%下降到1.4%（全球复检率2.4%），要求二次采样率为0.23%，阳性检出率为0.02%。通过流式细胞术研究了所有患者的淋巴细胞表型（T、B、NK 群体）、CD45RA/RO 同种型的表达、TCR αβ 和 TCR γ δ 的百分比和强度、HLA-DR+ T 淋巴细胞的存在以及体外淋巴细胞增殖。在接受筛查的 130,903 名新生儿中，30 名检测呈阳性，其中 15 名是男性。在研究期间，一名患者被诊断患有 SCID：发病率为加泰罗尼亚 130,903 名新生儿中的 1 名。 13 名患者患有临床显着的 T 细胞淋巴细胞减少症（非 SCID），发病率为 10,069 名新生儿中就有 1 名（阳性检测的 43%）。 9 名患者被认为是假阳性病例，因为最初淋巴细胞计数正常，且 TREC 在出生后 3 至 6 个月内恢复正常；4 名婴儿因最初淋巴细胞计数较低而出现短暂性淋巴细胞减少，但在接下来的几个月内恢复；3 名患者仍在研究中。获得的结果进一步证明了将这种疾病纳入新生儿筛查计划的好处。需要更长时间的随访来确定加泰罗尼亚 SCID 的确切发病率。
Severe combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the experience gained in the first year, and changed from 34 to 24 copies/mu L. This decreased the retest rate from 3.34 to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR alpha beta and TCR gamma delta, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive, 15 of which were male. During the study period, one patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, four infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and three patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia.