Primary Immune Deficiency Treatment Consortium

初级免疫缺陷治疗联盟

基本信息

批准号：
9123504
负责人：
MORTON COWAN
金额：
$ 152.85万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-12 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9123504
关键词：
Address Affect Antigens Asia Autoimmunity B-Lymphocytes Biological Markers Busulfan Cells Child Child Care Chimerism Chronic Granulomatous Disease Clinical Clinical Research Clinical Trials Consensus Country Cross-Sectional Studies Data Collection Defect Diagnosis Diagnostic Disease Dose Educational workshop Engraftment Enrollment Europe Faculty Family Funding Future Genetic Genotype Goals Heterogeneity Immune Immune system Immunity Immunobiology Immunodeficiency-Related Disorder Immunology Individual Infant Information Dissemination Inherited Institution International Late Effects Life Long-Term Survivors Longitudinal Studies Manuscripts Medical Molecular Biology Multicenter Studies Native Americans Natural History Navajo Neonatal Screening Newborn Infant Newly Diagnosed North America Outcome Parents Patient-Centered Care Patients Phenotype Pilot Projects Population Prospective Studies Protocols documentation Publications Publishing Quality of life Rare Diseases Regimen Research Personnel Reservations Retrospective Studies Scientist Senior Scientist Severe Combined Immunodeficiency Siblings Source South America Stem cells Surveys T-Lymphocyte Time Training Transplant Recipients Transplantation Conditioning Wiskott-Aldrich Syndrome base career development chemotherapy cohort congenital immunodeficiency enzyme replacement therapy exhaustion experience gene therapy hematopoietic cell transplantation improved interest operation patient advocacy group phase II trial prospective public health relevance reconstitution screening standard care survival outcome

项目摘要

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.

描述（由申请人提供）：原发性免疫缺陷（PID）是免疫系统中罕见的、危及生命的遗传性缺陷。原发性免疫缺陷治疗联盟 (PIDTC) 成立于 2009 年，目前代表北美 5 个患者倡导组织 (PAG) 和 33 个中心，在遗传学、分子生物学、免疫学、造血细胞移植 (HCT) 和基因治疗方面拥有广泛的专业知识（GT）、酶替代疗法（ERT）和医疗管理。 PAG 参与 PIDTC 的运作、受试者招募以及我们研究结果的信息传播。 PIDTC 重点关注可通过 HCT、ERT 或 GT 治愈的三种 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 的具体目标是：描述接受 HCT、ERT 和/或 GT 的 SCID、WAS 和 CGD 儿童的长期结局和晚期并发症；确定预测 SCID、WAS 和 CGD 儿童 HCT、ERT 和/或 GT 后结局的关键因素和生物标志物；定义 SCID 长期幸存者 HCT 后 T 和 B 细胞重建的免疫生物学；确定接受 HCT 的 SCID 儿童持续 T 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；确定哪些 CGD 患者最能从 HCT 中受益；培训PID临床研究的初级研究者；和。让 PAG 参与进来，并在患者、家长、临床医生和科学家之间分享有关 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 SCID 的横断面/回顾性研究，探索影响长期生存、免疫重建、迟发效应和生活质量 (Qo) 的因素。项目 3 探讨 CGD 中 HCT 后的早期和长期结果，确定哪些 CGD 患者最有可能从 HCT 中受益。项目 4 重点关注 WAS 中 HCT 后的早期和长期结果，以确定全面疾病纠正和包括生活质量在内的后期影响所需的供体嵌合程度。该试点项目将研究接受 HCT 的 WAS 患者的自身免疫生物标志物。这些研究将解决有关这些疾病的 HCT 的关键问题，并为未来的前瞻性临床试验奠定基础。