New England Newborn Screening Program, Commonwealth Medicine, University of Massachusetts Medical School, Worcester, Mass.
Division of Immunology, Boston Children's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
J Allergy Clin Immunol Pract. 2021 May;9(5):2060-2067.e2. doi: 10.1016/j.jaip.2021.02.006. Epub 2021 Feb 16.
Massachusetts began newborn screening (NBS) for severe combined immunodeficiency (SCID) using measurement of T-cell receptor excision circles (TRECs) from dried blood spots.
We describe developments and outcomes from the first 10 years of this program (February 1, 2009, to January 31, 2019).
TREC values, diagnostic, and outcome data from all patients screened for SCID were evaluated.
NBS of 720,038 infants prompted immunologic evaluation of 237 (0.03%). Of 237, 9 were diagnosed with SCID/leaky SCID (4% of referrals vs 0.001% general population). Another 7 were diagnosed with other combined immunodeficiencies, and 3 with athymia. SCID/leaky SCID incidence was approximately 1 in 80,000, whereas approximately 1 in 51,000 had severe T-cell lymphopenia for which definitive treatment was indicated. All patients with SCID/leaky SCID underwent hematopoietic cell transplant or gene therapy with 100% survival. One patient with athymia underwent successful thymus transplant. No known cases of SCID were missed. Compared with outcomes from the 10 years before SCID NBS, survival trended higher (9 of 9 vs 4 of 7), likely due to a lower rate of infection before treatment.
Our data support a single NBS testing-and-referral algorithm for all gestational ages. Despite lower median TREC values in premature infants, the majority for all ages are well above the TREC cutoff and the algorithm, which selects urgent (undetectable TREC) and repeatedly abnormal TREC values, minimizes referral. We also found that low naïve T-cell percentage is associated with a higher risk of SCID/CID, demonstrating the utility of memory/naïve T-cell phenotyping as part of follow-up flow cytometry.
马萨诸塞州开始使用干血斑检测 T 细胞受体切除环（TREC）的方法对严重联合免疫缺陷症（SCID）进行新生儿筛查（NBS）。
我们描述了该项目实施的前 10 年（2009 年 2 月 1 日至 2019 年 1 月 31 日）的进展和结果。
对所有接受 SCID 筛查的患者的 TREC 值、诊断和结果数据进行评估。
对 720038 名婴儿进行 NBS 检测后，对 237 名婴儿进行了免疫评估（0.03%）。其中 9 名被诊断为 SCID/渗漏性 SCID（转诊率为 4%，普通人群为 0.001%）。另有 7 名被诊断为其他联合免疫缺陷症，3 名被诊断为无胸腺。SCID/渗漏性 SCID 的发病率约为每 80000 例 1 例，而约有 1 例 51000 例存在严重 T 细胞淋巴细胞减少症，需要进行明确的治疗。所有 SCID/渗漏性 SCID 患者均接受造血干细胞移植或基因治疗，存活率为 100%。1 例无胸腺患者成功接受了胸腺移植。未漏诊 SCID 病例。与 SCID NBS 前 10 年的结果相比，生存率呈上升趋势（9 例中有 9 例，7 例中有 4 例），这可能是由于治疗前感染率较低所致。
我们的数据支持对所有胎龄采用单一的 NBS 检测和转诊算法。尽管早产儿的中位 TREC 值较低，但大多数婴儿的 TREC 值均远高于 TREC 截止值和算法，该算法选择紧急（无法检测到的 TREC）和反复异常的 TREC 值，从而最大限度地减少了转诊。我们还发现，幼稚 T 细胞百分比低与 SCID/CID 的风险增加相关，这表明记忆/幼稚 T 细胞表型分析作为随访流式细胞术的一部分具有实用性。
