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: 7624557
• 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/7624557
• 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.

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