Primary Immune Deficiency Treatment Consortium

描述（由申请人提供）：原发性免疫缺陷（pid）是一种罕见的、危及生命的免疫系统遗传缺陷。原发性免疫缺陷治疗联盟（PIDTC）成立于2009年，目前在北美拥有5个患者倡导团体（PAGs）和33个中心，在遗传学、分子生物学、免疫学、造血细胞移植（HCT）、基因治疗（GT）、酶替代治疗（ERT）和医疗管理方面拥有广泛的专业知识。PAGs参与PIDTC的运作、受试者招募和我们研究结果的信息传播。PIDTC的重点是三种可以用HCT、ERT或GT治愈的pid：严重联合免疫缺陷（SCID）、Wiskott - Aldrich综合征（WAS）和慢性肉芽肿病（CGD）。PIDTC的具体目的是：描述SCID、WAS和CGD患儿在接受HCT、ERT和/或GT治疗后的长期结局和晚期并发症；定义预测HCT、ERT和/或GT后SCID、WAS和CGD患儿预后的关键因素和生物学标志物；定义SCID长期存活患者HCT后T细胞和B细胞重构的免疫生物学；确定接受HCT治疗的SCID儿童持续T细胞和B细胞重建所需的最小化疗剂量，无论供体来源如何；在美国和其他国家推广新生儿SCID筛查；定义WAS患者自身免疫的生物标志物；确定从HCT中获益最多的CGD患者；培养初级研究人员进行PID临床研究；和。参与pag，并在患者、家长、临床医生和科学家之间分享关于pid诊断和治疗的最新方法的信息。项目1是一项针对典型和非典型SCID婴儿的前瞻性研究，旨在识别影响植入、早期免疫重建和存活的早期生物标志物和其他疾病或hct相关因素。项目2是一项SCID的横断面/回顾性研究，探讨影响长期生存、免疫重建、晚期效应和生活质量（Qo）的因素。项目3关注HCT治疗CGD后的早期和长期结果，确定哪些CGD患者最有可能从HCT中获益。项目4侧重于HCT在WAS中的早期和长期结果，以确定完全疾病纠正所需的供体嵌合程度和包括生活质量在内的晚期效应。该试点项目将研究接受HCT治疗的WAS患者自身免疫的生物标志物。这些研究将解决HCT治疗这些疾病的关键问题，并为未来的前瞻性临床试验奠定基础。

DESCRIPTION (provided by applicant): Primary immune deficiencies (PIDs) are rare, life-threatening inherited defects in the immune system. The Primary Immune Deficiency Treatment Consortium (PIDTC) was established in 2009 and currently represents 5 Patient Advocacy Groups (PAGs) and, 33 centers in North America with broad expertise in genetics, molecular biology, immunology, hematopoietic cell transplantation (HCT), gene therapy (GT), enzyme replacement therapy (ERT) and medical management. The PAGs participate in PIDTC operations, subject recruitment, and dissemination of information resulting from our studies. The PIDTC is focused on three PIDs that can be cured with HCT, ERT or GT: Severe Combined Immunodeficiency (SCID), Wiskott - Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). The Specific Aims of the PIDTC are: To characterize the long-term outcomes and late complications in children with SCID, WAS and CGD who undergo HCT, ERT and/or GT; To define the critical factors and biologic markers that predict the outcome of children with SCID, WAS and CGD following HCT, ERT and/or GT; To define the immunobiology of T and B cell reconstitution post HCT in long term survivors of SCID; To establish the minimal dose of chemotherapy necessary for sustained T and B cell reconstitution in children with SCID undergoing HCT regardless of donor source; To promote newborn screening for SCID in the US and other countries; To define biomarkers of autoimmunity in patients with WAS; To identify those patients with CGD who would most benefit from HCT; To train junior investigators in PID clinical research; and. To engage PAGs and share information between patients, parents, clinicians and scientists regarding the most up-to-date approaches to diagnosis and treatment of PIDs. Project 1 is a prospective study of typical and atypical SCID infants to identify early biomarkers and other disease- or HCT-related factors that affect engraftment, early immune reconstitution and survival. Project 2 is a cross-sectional/retrospective study of SCID, exploring factors that affect long term survival, immune reconstitution, late effects and quality of life (Qo). Project 3 addresses early and long-term outcomes following HCT in CGD, identifying which patients with CGD are most likely to benefit from HCT. Project 4 focuses on early and long-term outcomes following HCT in WAS to determine the degree of donor chimerism necessary for full disease correction and late effects including QoL. The Pilot Project will study biomarkers of autoimmunity in WAS patients undergoing HCT. These studies will resolve critical questions concerning HCT for these disorders and form the basis for future prospective clinical trials.