Pilot ProgramPilot/Demonstration Project Program (PPP)

初级免疫缺陷治疗联盟的试点项目计划(PPP)将 利用我们主要项目的基础，给年轻的研究人员提供发展的机会 新的研究计划。近期、近期和未来的试点项目将包括：新生儿筛查 建立一个分布式的“生物库”，其中包括PID样本和数据；以及前瞻性随机试验 针对特定的PID亚群的HCT方案。对于我们的第一个试点项目，SCID新生儿筛查，我们将 DNA干品中T细胞受体切除环(TRECs)定量检测T细胞淋巴细胞减少 血迹。TRECs存在于新形成的T细胞中，但在患有SCID的婴儿的血液中不存在 T细胞成熟受损的人。新生儿和诊断时干血的采集和检测 来自PIDTC婴儿的斑点将验证TREC方法识别SCID病例。此外，以人口为基础 将试行TREC筛查。纳瓦霍印第安人的一种创始人突变，导致2000年1/2000的新生儿患有SCID， 这使这一群体成为评估新生儿筛查一种其他非常罕见的疾病的理想人群。启动 在两家医院，并在整个纳瓦霍保护区扩大到6000名婴儿的目标，我们将进行 在母亲知情同意的情况下进行新生儿TREC检测。筛查异常的婴儿将得到最终的 检测SCID并转诊早期HCT(如果受到影响)。收集有价值的细胞、DNA和其他样本 来自PIDTC中心的患者，但每个PID的稀有性限制了在任何单个 地点。利用之前收集的样本并鼓励未来使用来自 PIDTC项目，将创建一个多中心样本库。来自所有项目的数据和样本以及调查结果 对样本进行的进一步研究(例如，SNP基因类型)将积累，从而使 样本集将随着时间的推移而增长。最后，将设计前瞻性、随机化、多中心治疗试验。 并由PIDTC调查人员执行。最初的焦点区域包括要耗尽的单抗 HCT前的特定淋巴亚群作为标准化疗的替代方案，以及特殊方案 新生儿筛查发现，患有SCID的健康但非常年轻的婴儿。

The Pilot Projects Program (PPP) in the Primary Immune Deficiency Treatment Consortium (PIDTC) will capitalize on the foundation of our main Projects and give opportunities to young investigators to develop new research initiatives. Immediate, near-term and future pilot projects will include: Newborn screening for SCID; Development of a distributed "biobank" of PID samples and data; and Prospective randomized trials of HCT protocols for particular PID subpopulations. For our first pilot project, SCID newborn screening, we will assay for T cell lymphocytopenia by quantitating T-cell receptor excision circles (TRECs) in DMA from dried blood spots. TRECs are present in newly formed T cells, but absent in the blood of infants with SCID, in whom T cell maturation is impaired. Collection and testing of newborn and time-of-diagnosis dried blood spots from PIDTC infants will validate the TREC method for identifying SCID cases. Also, population-based TREC screening will be piloted. A founder mutation in Navajo Indians, resulting in SCID in 1/2000 births, makes this an ideal population for evaluating newborn screening for an otherwise very rare disease. Starting in 2 hospitals and expanding throughout the Navajo Reservation to target of 6000 infants, we will conduct neonatal TREC testing with maternal informed consent. Infants with abnormal screens will receive definitive testing for SCID and referral for early HCT if affected. Valuable cells, DNA and other samples are collected from patients at PIDTC centers, but the rarity of each PID has limited the research possible at any single site. To take advantage of previously collected samples and encourage future research with samples from PIDTC Projects, a multicenter sample bank will be created. Data and samples from all Projects plus findings from further studies conducted on the samples (e.g. SNP genotypes) will accrue so that the value of the sample set will grow over time. Finally, prospective, randomized, multicenter treatment trials will be designed and preformed by PIDTC investigators. Areas of initial focus include monoclonal antibodies to deplete specific lymphoid subsets prior to HCT as an alternative to standard chemotherapy, and special protocols for healthy, but very young infants with SCID, discovered by newborn screening.