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.

Public Health Relevance

Primary immune deficiencies (PIDs) are rare, life-threatening inherited defects in the immune system. The PIDTC is the only organization of it's kind in North America with projects that compare different treatment approaches that will result in improved survival and outcome for future patients with these disorders.

Agency
National Institute of Health (NIH)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54AI082973-06
Application #
8765060
Study Section
Special Emphasis Panel (ZTR1)
Program Officer
Griffith, Linda M
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Long-Boyle, Janel R; Savic, Rada; Yan, Shirley et al. (2015) Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use. Ther Drug Monit 37:236-45
Haddad, Elie; Allakhverdi, Zoulfia; Griffith, Linda M et al. (2014) Survey on retransplantation criteria for patients with severe combined immunodeficiency. J Allergy Clin Immunol 133:597-9
Shearer, William T; Dunn, Elizabeth; Notarangelo, Luigi D et al. (2014) Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience. J Allergy Clin Immunol 133:1092-8
Dvorak, Christopher C; Hassan, Amel; Slatter, Mary A et al. (2014) Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. J Allergy Clin Immunol 134:935-943.e15
Lee, Yu Nee; Frugoni, Francesco; Dobbs, Kerry et al. (2014) A systematic analysis of recombination activity and genotype-phenotype correlation in human recombination-activating gene 1 deficiency. J Allergy Clin Immunol 133:1099-108
Pai, Sung-Yun; Cowan, Morton J (2014) Stem cell transplantation for primary immunodeficiency diseases: the North American experience. Curr Opin Allergy Clin Immunol 14:521-6
Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D et al. (2014) Primary Immune Deficiency Treatment Consortium (PIDTC) report. J Allergy Clin Immunol 133:335-47
Medical Advisory Committee of the Immune Deficiency Foundation; Shearer, William T; Fleisher, Thomas A et al. (2014) Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol 133:961-6
Chinen, Javier; Notarangelo, Luigi D; Shearer, William T (2014) Advances in basic and clinical immunology in 2013. J Allergy Clin Immunol 133:967-76
Pai, Sung-Yun; Logan, Brent R; Griffith, Linda M et al. (2014) Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med 371:434-46

Showing the most recent 10 out of 33 publications