Project Summary Primary immune deficiencies (PIDs) are a group of over 480 rare disorders of the immune system that result in increased susceptibility to infections, autoimmunity, and malignancies. The most severe forms of PIDs are fatal unless immune reconstitution is achieved by hematopoietic cell transplantation (HCT) or gene therapy. In 2009, the Primary Immune Deficiency Treatment Consortium (PIDTC) was established to conduct retrospective and prospective studies of risk factors, long term outcomes and late effects in individuals with severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), and chronic granulomatous disease (CGD); with the 2019 funding cycle a protocol to study primary immune regulatory disorders (PIRD) was added. Because individual PIDs are rare, multicenter collaborations are needed to systematically collect detailed data to study outcomes and to develop clinical trials to determine the best interventions. Annual Workshops, starting in 2011, and continuously funded by R13 awards from NIAID, have brought together participating investigators from the PIDTC sites, now comprising 47 academic centers across the US and Canada. These Workshops and Education Days, the latter added in 2016 to encourage and train a diverse group of new experts, fosters interaction between physicians, basic scientists, patient advocates, and engage trainees who then become leaders. This application requests continuation of R13 support for PIDTC Workshops for the coming 3 years. The proposed 13th PIDTC Scientific Workshop and Education Day in Cincinnati, Ohio (PIDTC2023) will be themed “New Treatments for Primary Immune Disorders.” We will offer topics including cellular therapies for infections, graft vs. host disease, gene therapy, and development of clinical trials. Plans for the two following workshops in 2023 and 2024 are described. The specific objectives are: 1. Collect, analyze and disseminate information on survival, clinical status, and immune function in patients with PIDs who have received HCT or other forms of treatment. 2. Establish biological markers to predict successful immune reconstitution following treatments. 3. Evaluate novel approaches to treatment for PIDs that minimize HCT-related toxicity while fostering robust and durable engraftment and immune reconstitution. 4. Develop optimal treatment protocols for infants with SCID identified by newborn screening. 5. Develop clinical trials to define best practices for treatment of PIDs. 6. Encourage trainees to become the next generation of PID experts. 7. Recruit and train underrepresented minority physicians to the field of PID. 8. Increase synergy between scientists, physicians, and patient advocates from diverse backgrounds to improve PID awareness and public education.