Primary Immune Deficiency Treatment Consortium

初级免疫缺陷治疗联盟

• 批准号: 8912350
• 负责人: MORTON COWAN
• 金额: $ 154.35万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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/8912350
• 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

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）在免疫系统中很少见，威胁生命的遗传缺陷。主要的免疫缺陷治疗联盟（PIDTC）于2009年成立，目前代表5个患者倡导组（PAG）和33个北美中心，在北美具有广泛的遗传学专业知识，分子生物学，免疫学，造血细胞（HCT），基因治疗（GT），enzeme替代治疗（ENZEME REPLAST）和替代。 PAG参与了PIDTC操作，受试者招募以及我们研究产生的信息的传播。 PIDTC专注于可以用HCT，ERT或GT治愈的三个PID：严重的合并免疫缺陷（SCID），Wiskott -Aldrich综合征（WAS）和慢性肉芽肿性疾病（CGD）。 PIDTC的具体目的是：表征SCID，SCID儿童的长期结局和晚期并发症，以及接受HCT，ERT和/或GT的CGD；定义HCT，ERT和/或GT之后，预测SCID，SCID儿童和CGD结果的关键因素和生物标记；在SCID的长期幸存者中，定义了T和B细胞重建后的免疫生物学；为了确定在患有HCT的儿童中持续T和B细胞重建所必需的化学疗法的最低剂量，而不管供体来源如何；在美国和其他国家 /地区促进新生儿筛查；定义患有IS患者自身免疫性的生物标志物；识别那些最能从HCT中受益的CGD患者；培训初级调查人员的PID临床研究；和。参与PAG并在患者，父母，临床医生和科学家之间共享有关PID诊断和治疗最新方法的信息。项目1是对典型和非典型SCID婴儿的前瞻性研究，旨在鉴定影响植入，早期免疫重建和生存的早期生物标志物以及其他疾病或HCT相关的因素。项目2是对SCID的横断面/回顾性研究，探索影响长期生存，免疫重建，迟到效果和生活质量（QO）的因素。项目3解决了CGD HCT后的早期和长期结局，确定哪些CGD患者最有可能受益于HCT。项目4的重点是HCT之后的早期和长期结局，以确定全部疾病矫正和包括QOL在内的晚期作用所必需的供体嵌合的程度。试点项目将研究接受HCT的患者自身免疫的生物标志物。这些研究将解决有关这些疾病HCT的关键问题，并为未来的前瞻性临床试验构成基础。