The Primary Immune Deficiency Treatment Consortium (PIDTC), an RDCRN consortium of 44 immunology and hematopoietic stem cell transplant centers throughout the USA and Canada, was established in 2009 to study rare genetic disorders of the immune system, collectively known as primary immunodeficiency diseases (PIDs). The goals of the PIDTC are to understand PIDs and define optimal approaches for their definitive treatment. In its first 9 years, the PIDTC has studied outcomes following hematopoietic cell transplantation (HCT), gene therapy (GT) and enzyme replacement therapy (ERT) for patients with severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD). These PIDs were chosen because they have been among the most life-threatening and difficult to treat, often requiring HCT for survival. Because no single center follows enough affected individuals to encompass the full spectrum of these disorders, a consortium is essential to define the natural history of each PID. Moreover, historically, individual centers developed their own approaches to treatment, without consensus regarding indications or timing for HCT, types of conditioning regimens, or sources of donor cells. Thus, multicenter studies are required for robust statistical assessment to compare impacts not only of patient-related variables, but also of treatment-related variables on clinical outcome. The PIDTC is organized to develop, perform and learn from multicenter studies. Our major contributions to understanding of PID pathogenesis and defining which treatments produce optimal clinical outcomes have been published in 111 papers. Close relationships with multiple Patient Advocacy Groups (PAGs) have led to publications on high-priority issues for affected individuals and their families, including quality of life and long-term outcomes. PIDTC Pilot Projects have advanced newborn screening for SCID and introduced important mechanistic studies, while our Career Enhancement Core has held an annual PIDTC Scientific Workshop and Education Day and has supported 20 PID trainees, all of whom remain active in academic research. PIDTC studies of SCID have enabled our design and implementation of the first prospective multicenter trial to determine the minimal dose of busulfan conditioning to achieve T and B cell immune reconstitution. Looking forward, the PIDTC will undertake a new initiative to study Primary Immune Regulatory Disorders (PIRD) as it continues its studies of SCID and CGD. The major impact of the proposed research will be establishment of baseline data and organizational structures to undertake multicenter clinical trials that will apply improved basic understanding to achieve further evidence-based advances in the care of PIDs.

Public Health Relevance

Primary Immune Deficiencies (PIDs) are genetic defects of the immune system that have high risks for infectious and autoimmune/autoinflammatory complications. The Primary Immune Deficiency Treatment Consortium (PIDTC) is defining the natural history of PIDs and their responses to the spectrum of available therapies (hematopoietic cell transplant, gene therapy, enzyme replacement therapy, biological agents and molecularly- targeted small molecule drugs). Because PIDs are rare, a multi-institutional consortium is essential to encompass the full spectrum of PIDs. In close association with patient advocacy groups and with highly active career enhancement and pilot and feasibility programs, the PIDTC is improving the understanding, clinical management and outcomes for patients with PIDs.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54AI082973-11
Application #
9804604
Study Section
Special Emphasis Panel (ZTR1)
Program Officer
Griffith, Linda M
Project Start
2009-09-12
Project End
2024-08-31
Budget Start
2019-09-13
Budget End
2020-08-31
Support Year
11
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Chinen, Javier; Cowan, Morton J (2018) Advances and highlights in primary immunodeficiencies in 2017. J Allergy Clin Immunol 142:1041-1051
Miggelbrink, Alexandra M; Logan, Brent R; Buckley, Rebecca H et al. (2018) B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation. Blood 131:2967-2977
Slack, James; Albert, Michael H; Balashov, Dmitry et al. (2018) Outcome of hematopoietic cell transplantation for DNA double-strand break repair disorders. J Allergy Clin Immunol 141:322-328.e10
Langelier, Charles; Zinter, Matt S; Kalantar, Katrina et al. (2018) Metagenomic Sequencing Detects Respiratory Pathogens in Hematopoietic Cellular Transplant Patients. Am J Respir Crit Care Med 197:524-528
Haddad, Elie; Logan, Brent R; Griffith, Linda M et al. (2018) SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood 132:1737-1749
Barzaghi, Federica; Amaya Hernandez, Laura Cristina; Neven, Benedicte et al. (2018) Long-term follow-up of IPEX syndrome patients after different therapeutic strategies: An international multicenter retrospective study. J Allergy Clin Immunol 141:1036-1049.e5
Kuo, Caroline Y; Long, Joseph D; Campo-Fernandez, Beatriz et al. (2018) Site-Specific Gene Editing of Human Hematopoietic Stem Cells for X-Linked Hyper-IgM Syndrome. Cell Rep 23:2606-2616
Belderbos, Mirjam E; Gennery, Andrew R; Dvorak, Christopher C et al. (2018) Outcome of domino hematopoietic stem cell transplantation in human subjects: An international case series. J Allergy Clin Immunol 142:1628-1631.e4
Buchbinder, David; Smith, Matthew J; Kawahara, Misako et al. (2018) Application of a radiosensitivity flow assay in a patient with DNA ligase 4 deficiency. Blood Adv 2:1828-1832
Kohn, Donald B; Hershfield, Michael S; Puck, Jennifer M et al. (2018) Consensus approach for the management of severe combined immune deficiency caused by adenosine deaminase deficiency. J Allergy Clin Immunol :

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