Primary Immune Deficiency Treatment Consortium

初级免疫缺陷治疗联盟

• 批准号: 8765060
• 负责人: MORTON COWAN
• 金额: $ 124.95万
• 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/8765060
• 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; Phase II Clinical Trials; 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; 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）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5个患者倡导小组（PAG）和北美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），酶替代疗法（ERT）和医疗管理方面拥有广泛的专业知识。PAG参与PIDTC操作、受试者招募和我们研究产生的信息传播。PIDTC关注三种可用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HCT、ERT和/或GT后SCID、WAS和CGD儿童结局的关键因素和生物标志物;确定SCID长期存活者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;促进美国和其他国家的新生儿SCID筛查;确定WAS患者自身免疫的生物标志物;确定最能从HCT获益的CGD患者;培训PID临床研究的初级研究人员;和.参与PAG并在患者，父母，临床医生和科学家之间分享关于最新的PID诊断和治疗方法的信息。项目1是一项典型和非典型SCID婴儿的前瞻性研究，以确定影响植入、早期免疫重建和生存的早期生物标志物和其他疾病或HCT相关因素。项目2是一项关于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讨论了CGD中HCT后的早期和长期结局，确定哪些CGD患者最有可能从HCT中获益。项目4重点关注WAS患者HCT后的早期和长期结局，以确定完全疾病纠正和晚期效应（包括QoL）所需的供体嵌合体程度。试点项目将研究接受HCT的WAS患者的自身免疫生物标志物。这些研究将解决这些疾病的HCT相关关键问题，并为未来的前瞻性临床试验奠定基础。