WI State Public Health Lab Capacity for SCID Screening

威斯康星州公共卫生实验室 SCID 筛查能力

• 批准号: 7906714
• 负责人: Charles Dennis Brokopp
• 金额: $ 43.96万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2011-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7906714
• 关键词: WI; State; Public; Health; Lab

DESCRIPTION (provided by applicant): Project Summary/Abstract The project will conduct research to develop, evaluate and/or improve routine newborn blood spot screening tests for forms of Severe Combined Immuno Deficiencies (SCID). It will continue for three years, a full scale-fully integrated, SCID pilot program testing all Wisconsin newborns within the NBS program. It will disseminate knowledge and expertise to promote and facilitate SCID-NBS testing. Severe combined immune deficiency (SCID) is a group of life-threatening genetic disorders that occur in an estimated 1 in 66,000 live births. Hematopoietic stem cell transplantation (HSCT) is highly curative (up to 95% survival) only if the SCID infants are recognized early in life, prior to the acquisition of severe infections. SCID infants appear normal at birth and often have no family history. Hence, most SCID infants are not recognized until diagnosed with life-threatening opportunistic infections, resulting in substantial morbidities and reduced overall survival of 50-70% Thus, the ability to detect newborns prior to the acquisition of infections has tremendous population health impact. During T cell development in the thymus, normal productive rearrangement of the T-cell receptor generates T-cell receptor excision circles (TRECs) which are present in ~70% of all peripheral naove T- cells(nn,nn). Importantly, all of the known genetic SCID defects lead to severe naove T-cell lymphopenia. In 2006-7, we performed two large-scale studies to determine the feasibility of quantitating TRECs using dried blood spots (DBS) to detect SCID newborns. Based on the success of these pilot studies, which demonstrated the ability to detect blinded SCID samples and a low screening positive rate of ~0.02%, the State of Wisconsin initiated a pilot, prospective newborn screening for SCID on January 1st 2008(nn,nn, nn). Based on these early results, we hypothesize that NBS for SCID by TREC analysis will be a highly robust, sensitive, and cost-effective means of positively identifying SCID within the newborn period. Our proposed approach will not only demonstrate the feasibility of routine NBS for SCID but will research and establish a) a documented testing methodology, b) critical baseline data, i.e. incidence rates, reference ranges, quality assurance protocols, c) referral practices, etc., and d) demonstrate a complete SCID program --- testing, diagnosis and treatment. "a-d" are critical to validating the test methodology but also needed to encourage and facilitate the adoption of SCID testing by other states' NBS programs. When confirmed by a repeat, duplicate TRECs assay and 2-actin measurement, (both on the initial DBS), a second whole blood specimen is assessed by flow cytometry (CD3, CD4, CD8, CD19, CD56, CD45 and CD45RO); low counts warrant immediate referral and assessment at the Immune Deficiency Clinic at CHW. "Data sharing," publication and one-on-one collaboration with other state NBS programs will freely disseminate knowledge and expertise and facilitate national adoption of SCID testing. PUBLIC HEALTH RELEVANCE: Project Narrative - relevance to public health Severe combined immunodeficiency (SCID) is an asymptomatic, insidious disease which, untreated, is 100% fatal; SCID can be detected by routine newborn screening (NBS), a vital public health program currently implemented in all 50 states. Properly treated, by bone marrow transplant at less than three months, cure rates of 95% are claimed. 2007 WI data shows the differential cost of treating 5 clinically diagnosed SCID babies and one diagnosed at one week is $2,200,000 each vs $250,000; between 40 and 160 SCID babies (true incidence is unknown) are born in the US each year. NBS for SCID meets the Healthy People 2010 (Maternal, infant and health) mandates to "reduce infant deaths" and "to ensure appropriate newborn blood spot screening." We propose a three year project with dual goals: to implement a full scale pilot testing program fully within the Wisconsin State Public Health Laboratory's Newborn Screening Program (concurrent with testing for 47 other conditions) and by doing so demonstrating not only the efficacy of NBS for SCID but also creating a model showing the feasibility of, and requirements for, adding SCID to existing programs in other states. Our SCID-NBS program will not only produce essential baseline data (i.e. incidence rates in the target population), it will detect SCID afflicted newborns born in year 01 through 03.

描述（由申请人提供）： 项目摘要/摘要该项目将进行研究，以开发，评估和/或改善严重合并免疫缺陷（SCID）形式的常规新生儿血点筛查测试。它将持续三年，这是一项全面整合的SCID试点计划，测试NBS计划中的所有威斯康星州新生儿。它将传播知识和专业知识，以促进和促进SCID-NBS测试。严重的合并免疫缺陷（SCID）是一组威胁生命的遗传疾病，估计在66,000个活产中估计有1例。造血干细胞移植（HSCT）只有在获得严重感染之前识别出SCID婴儿的早期识别，才能高度治愈（最高95％的存活率）。 SCID婴儿出生时看起来正常，而且通常没有家族史。因此，在诊断出威胁生命的机会感染之前，大多数SCID婴儿才被识别，从而导致大量病毒性和50-70％的总体生存率降低，因此在获取新生儿之前发现新生儿的能力受到感染的能力产生了巨大的人群健康影响。在胸腺中T细胞发育过程中，T细胞受体的正常生产重排会产生T细胞受体切除圈（TREC），这些圆（TREC）存在于所有外围NAOVE T-细胞（NN，NN）中约70％。重要的是，所有已知的遗传性SCID缺陷导致严重的NAOVE T细胞淋巴细胞减少症。在2006 - 7年，我们进行了两项大规模研究，以确定使用干血点（DBS）定量TREC的可行性，以检测SCID新生儿。基于这些初步研究的成功，这些研究表明了检测盲型SCID样本的能力，较低的筛查率为〜0.02％，威斯康星州发起了一项试验，前瞻性新生儿筛查于2008年1月1日（NN，NN，NN，NN，NN）。基于这些早期结果，我们假设通过TREC分析进行SCID的NB将是一种高度鲁棒，敏感和成本效益的方法，可以在新生儿期间积极识别SCID。我们提出的方法不仅将证明常规NBS对SCID的可行性，还将研究和建立a）记录的测试方法，b）关键基线数据，即发病率，参考范围，质量保证协议，c）转诊实践等，以及D）表现出一个完整的SCID计划----测试，诊断，诊断和治疗。 “ A-D”对于验证测试方法至关重要，但也需要鼓励和促进其他州的NBS计划采用SCID测试。通过重复确认，重复的TRECS分析和2-肌动蛋白测量（均在初始DBS上），通过流式细胞仪（CD3，CD4，CD8，CD8，CD19，CD19，CD56，CD45和CD45RO）评估第二个全血样。低计数需要在CHW的免疫缺陷诊所立即转诊和评估。 “数据共享”，出版物和与其他州NBS计划的一对一合作将自由传播知识和专业知识，并促进全国采用SCID测试。 公共卫生相关性： 项目叙述 - 与公共卫生的相关性严重的联合免疫缺陷（SCID）是一种无症状的，阴险的疾病，未经治疗是100％致命的；可以通过常规新生儿筛查（NB）检测到SCID，这是目前在所有50个州实施的重要公共卫生计划。通过不到三个月的骨髓移植对骨髓移植进行了适当的治疗，据称治愈速率为95％。 2007年WI数据显示，治疗5例临床诊断的SCID婴儿的差异成本，一个被诊断为一周的婴儿为$ 2,200,000，$ 250,000；每年美国出生的40至160个SCID婴儿（真正的发生率是未知的）。 SCID的NBS符合2010年健康人（母亲，婴儿和健康）的要求，要求“减少婴儿死亡”和“确保适当的新生儿血点筛查”。我们提出了一个具有双重目标的三年项目：在威斯康星州公共卫生实验室的新生儿筛查计划（与其他47个其他条件的测试同时）中，完全实施一项全尺度的试点测试计划，并通过这样做不仅表明NBS对SCID的功效表明，而且还创建了一个模型，显示出对现有计划的可行性，以及在其他州中增加了Scid的要求。我们的SCID-NBS计划不仅会产生必需的基线数据（即目标人群的发病率），还将检测到SCID遭受的新生儿在01年至03年中出生的新生儿。