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)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
2U54AI082973-06
Application #
8765060
Study Section
Special Emphasis Panel (ZTR1)
Program Officer
Griffith, Linda M
Project Start
2009-09-12
Project End
2019-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
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
Burbank, Allison J; Shah, Shaili N; Montgomery, Maureen et al. (2016) Clinically focused exome sequencing identifies an homozygous mutation that confers DOCK8 deficiency. Pediatr Allergy Immunol 27:96-8
Cowan, Morton J (2016) The Primary Immune Deficiency Treatment Consortium: how can it improve definitive therapy for PID? Expert Rev Clin Immunol 12:1007-9
Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D et al. (2016) Primary Immune Deficiency Treatment Consortium (PIDTC) update. J Allergy Clin Immunol 138:375-85
Chan, Alice Y; Punwani, Divya; Kadlecek, Theresa A et al. (2016) A novel human autoimmune syndrome caused by combined hypomorphic and activating mutations in ZAP-70. J Exp Med 213:155-65
De Ravin, Suk See; Wu, Xiaolin; Moir, Susan et al. (2016) Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med 8:335ra57
Jackson, Shaun W; Scharping, Nicole E; Jacobs, Holly M et al. (2016) Cutting Edge: BAFF Overexpression Reduces Atherosclerosis via TACI-Dependent B Cell Activation. J Immunol 197:4529-4534
Punwani, Divya; Kawahara, Misako; Yu, Jason et al. (2016) Lentivirus Mediated Correction of Artemis-deficient Severe Combined Immunodeficiency. Hum Gene Ther :
Punwani, Divya; Zhang, Yong; Yu, Jason et al. (2016) Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B. N Engl J Med 375:2165-2176
Merkel, Peter A; Manion, Michele; Gopal-Srivastava, Rashmi et al. (2016) The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis 11:66
Chinen, Javier; Notarangelo, Luigi D; Shearer, William T (2016) Advances in clinical immunology in 2015. J Allergy Clin Immunol 138:1531-1540

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