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: 7687552
• 负责人: Charles Dennis Brokopp
• 金额: $ 49.97万
• 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/7687552
• 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）： 该项目将进行研究，以开发，评估和/或改进常规新生儿血斑筛查测试的形式严重联合免疫缺陷（SCID）。它将持续三年，一个全面的，完全集成的，SCID试点计划测试所有威斯康星州新生儿在NBS计划。它将传播知识和专门知识，以促进和便利国家统计局的SCID-NBS测试。严重联合免疫缺陷（SCID）是一组危及生命的遗传性疾病，估计每66，000名活产婴儿中就有1人发生。造血干细胞移植（HSCT）是高度治愈（高达95%的生存率），只有当SCID婴儿在生命早期，在收购严重感染。SCID婴儿在出生时表现正常，通常没有家族史。因此，大多数SCID婴儿直到被诊断出患有威胁生命的机会性感染才被识别，导致大量的发病率和50-70%的总存活率降低。因此，在获得感染之前检测新生儿的能力具有巨大的群体健康影响。在胸腺中的T细胞发育期间，T细胞受体的正常生产性重排产生T细胞受体切除环（TREC），其存在于约70%的所有外周原始T细胞（nn，nn）中。重要的是，所有已知的遗传性SCID缺陷都会导致严重的幼稚T细胞淋巴细胞减少症。在2006- 2007年，我们进行了两项大规模的研究，以确定使用干血斑（DBS）定量TRECs检测SCID新生儿的可行性。基于这些试点研究的成功，这些研究证明了检测设盲SCID样本的能力和~ 0.02%的低筛查阳性率，威斯康星州于2008年1月1日启动了一项试点，前瞻性新生儿SCID筛查（nn，nn，nn）。基于这些早期的结果，我们假设NBS通过TREC分析的SCID将是一种高度稳健、敏感和具有成本效益的方法，可以在新生儿期内积极识别SCID。我们提出的方法不仅将证明常规NBS用于SCID的可行性，而且将研究和建立a）记录的检测方法，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）展示完整的SCID程序-检测、诊断和治疗。“a-d”是验证测试方法的关键，但也需要鼓励和促进其他州的NBS项目采用SCID测试。当通过重复、两次TRECs测定和2-肌动蛋白测量（均在初始DBS上）确认时，通过流式细胞术评估第二份全血样本（CD 3、CD 4、CD 8、CD 19、CD 56、CD 45和CD 45 RO）;低计数需要立即转诊到CHW免疫缺陷诊所进行评估。“数据共享”、出版物以及与其他国家国家统计局项目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： 严重联合免疫缺陷（SCID）是一种无症状、隐匿性疾病，未经治疗，100%致命; SCID可以通过常规新生儿筛查（NBS）检测出来，NBS是目前在所有50个州实施的重要公共卫生计划。在不到三个月的时间内通过骨髓移植进行适当治疗，治愈率为95%。2007年WI数据显示，治疗5名临床诊断的SCID婴儿和1名在一周内诊断的婴儿的差异成本分别为2，200，000美元和250，000美元;每年在美国出生的SCID婴儿在40到160之间（真实发病率未知）。国家统计局的SCID符合《2010年健康人民》（孕产妇、婴儿和健康）的要求，即“减少婴儿死亡”和“确保适当的新生儿血斑筛查”。“我们提出了一个为期三年的项目，具有双重目标：在威斯康星州州公共卫生实验室的新生儿筛查计划中全面实施一个全面的试点测试计划（同时测试47种其他条件），并通过这样做不仅证明了NBS对SCID的有效性，而且还创建了一个模型，显示了将SCID添加到其他州现有计划中的可行性和要求。我们的SCID-NBS项目不仅将产生基本的基线数据（即目标人群的发病率），还将检测01年至03年出生的患有SCID的新生儿。