# Primary Immune Regulatory Disorders: Clinical Presentations, Treatments and Outcomes

> **NIH NIH U54** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $57,878

## Abstract

PIDTC Project 6906 PIRD – Abstract
Primary Immune Regulatory Disorders (PIRD) are a group of immune diseases characterized predominantly by
immune dysregulation leading to organ-specific autoimmunity, excessive inflammation, and non-malignant
lymphoproliferation. Unlike classical primary immunodeficiencies, susceptibility to infections is typically less
prominent in these disorders. Causal gene defects that impact critical immune regulatory mechanisms, e.g.
regulatory T cell (Treg) function, key cytokine signaling pathways, and vital growth and differentiation
mechanisms, have now been identified in many patients with PIRD. Examples include FOXP3 in the Immune
dysregulation, Polyendocrinopathy, Enteropathy, X--linked (IPEX) syndrome, CTLA4 in CTLA4 haplo-
insufficiency, STAT1 and STAT3 in STAT1 or STAT3 gain-of-function (GOF) diseases, but there are now many
others. In fact, disorders with a PIRD phenotype constitute the fastest growing subset of newly-identified genetic
immunodeficiencies. The clinical severity of PIRD disorders often requires aggressive therapy to prevent
long-term damage, disability, or death. There is, however, no consensus regarding the best approach to
diagnose and treat PIRD, including which immune modulating drugs are most effective, and whether
hematopoietic cell transplantation (HCT) can be curative. We and others have shown that HCT can be curative
for some PIRD disorders. There is however no consensus regarding the best HCT approach and little information
about the unique challenges of HCT in PIRD. There also remains a significant need to define key clinical and
laboratory features that distinguish patients who will benefit most from HCT or from targeted immunomodulatory
treatments. We propose to evaluate the spectrum of clinical presentations, disease evolution, therapeutic
responsiveness, HCT approaches, HCT outcomes, and quality of life in PIRD patients. The objective of this
proposal is to answer key questions related to the diagnosis, care, and outcome of PIRD, while also investigating
basic mechanisms of disease pathogenesis and therapeutic responsiveness. All patients will be identified based
on a defined set of clinical criteria. Some patients who meet these criteria will have a defect in a gene known to
be associated with PIRD, while others will not. Patients will be evaluated together as a cohort and subanalyses
will be performed to compare patients with and without an identified genetic defect. The impact of the proposed
research is that it will answer key questions that will 1) accelerate diagnosis and increase our understanding of
this emerging subset of immune disorders; 2) directly guide the therapeutic approach utilized for PIRD; 3) lead
to the design of clinical trials to establish new therapies, since several of the underlying molecular defects are
already targets of immunomodulators under development or currently in use, and 4) inform the treatment of
autoimmune disorders more broadly.

## Key facts

- **NIH application ID:** 10018650
- **Project number:** 5U54AI082973-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** TROY R TORGERSON
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $57,878
- **Award type:** 5
- **Project period:** 2009-09-12 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018650

## Citation

> US National Institutes of Health, RePORTER application 10018650, Primary Immune Regulatory Disorders: Clinical Presentations, Treatments and Outcomes (5U54AI082973-12). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10018650. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*