The Primary Immune Deficiency Treatment Consortium (PIDTC) was established in 2009 as a collaborafion among North American centers with expertise in treating infants and children with rare, but serious primary immunodeficiencies (PIDs). While life-saving therapies, including hematopoiefic cell transplantafion (HCT), have been used for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS) and chronic granulomatous disease (CGD), these condifions remain so rare that single centers are unable to perform clinical studies to define the best treatments. The PIDTC has developed protocols to study systematically the diagnosis, treatment and outcomes of patients with these conditions who are followed throughout North America. The goal ofthe PIDTC Pilot Project Program is to take maximum advantage of new clinical research opportunities in rare primary immunodeficiencies (PIDs) to further promote the goals and objecfives ofthe PIDTC. Specifically, projects are preferenfially selected thatwill (a) establish new biomarkers predictive of PID outcomes;(b) generate feasibility data for future PIDTC aims arid protocols, including clinical trials;(c) address questions that are important to our patients, pafient advocacy groups (PAGs) and stakeholders;and (d) encourage early faculty to apply their talents in the fields of PID immunology and therapeufics, including opfimizafion of hematopoietic cell transplantafion (HCT) and other therapies. During its first 4 years, PIDTC Pilot Projects addressed newborn screening and B cell reconstitufion after transplantafion for SCID, and a current project explores why immunity in some post-HCT pafients wanes after initial success. Dr. David Rawlings is the PI ofthe proposed pilot project, "Analysis of B cell tolerance in Wiskott-Aldrich svndrome followincf stem cell transplant". A significant proportion (up to 20%) of pafients with WAS develop severe, humoral autoimmunity following HCT and this complicafion correlates with mixed donor chimerism including lower levels of donor myeloid cells. A mechanisfic explanafion behind these observations, however, has been lacking.
The Specific Aims of this study are to: a) Determine whether post-HCT autoimmunity correlates with skewed B vs. T cell donor chimerism;b) Determine whether post-HCT autoimmunity correlates with serum BAFF or APRIL levels;and, c) Determine whether post-HCT autoimmunity is preceded by evidence for B cell activation, serum autoanfibodies, and/or an altered B and T cell repertoire. This pilot study will begin to analyze key biomarkers the may predict autoimmunity in WAS pafients post-HCT and will confinue in years 8-10.

Public Health Relevance

The PIDTC Pilot Project Program research projects are a key strategic aspect ofthe PIDTC, enriching the established aims of our protocols and revealing important areas ripe to be addressed in future aims and spin-off protocols. The proposed project on autoimmunity in patients with WAS will focus on critical biomarkers that predict outcome in this rare primary immunodeficiency and could positively impact other disorders with autoimmune manifestafions.

National Institute of Health (NIH)
Specialized Center--Cooperative Agreements (U54)
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University of California San Francisco
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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

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