# Novel Primary Immunodeficiency Disease Due to IL27RA Deficiency

> **NIH NIH R21** · BAYLOR COLLEGE OF MEDICINE · 2022 · $200,625

## Abstract

Defects in over 400 genes have been identified as causes of primary immunodeficiency diseases. The
molecular etiologies of many primary immunodeficiency diseases nevertheless remain unknown. This gap in
knowledge impairs our ability to diagnose and properly treat affected patients. A critical need therefore exists
for enhanced understanding of the genetic basis and mechanisms of primary immunodeficiency diseases. The
objective of this application is to use cutting-edge genomic and molecular technologies to investigate a novel
primary immunodeficiency disease, [GRAnulomas, Low T cells, and Short stature (GRALTS)], associated with
biallelic pathogenic variants in IL27RA. The central hypothesis of this application is that IL27RA deficiency
causes GRALTS. This hypothesis will be tested with 3 specific aims: 1) To define the effect of the variants
on IL27RA expression in T cells, 2) To determine the impact of the variants on IL27RA function in T cells,
and 3) Elucidate the downstream outcomes of impaired IL-27 signaling. The proposed work is innovative
because defects in IL-27 signaling have not previously been shown to cause human disease. It is significant
because it will validate IL27RA deficiency as a novel underlying cause of human primary immunodeficiency
disease. Thus, this project is expected to have an important positive impact because it will augment our ability
to appropriately recognize and treat primary immunodeficiency disease patients who have IL27RA deficiency.
The information gained is anticipated to improve our ability to functionally assess and validate biallelic variants
of uncertain significance in IL27RA and enhance our understanding of the importance of IL-27 signaling in
human T cell function. The proposed research is therefore relevant to the mission of the NIH and this RFA
because it focuses upon the investigation of a novel cause of human disease to gain fundamental knowledge
that will facilitate reduction in the burden of illness and disability and improvement in the lives of patients who
have this condition and related primary immunodeficiency diseases.

## Key facts

- **NIH application ID:** 10311550
- **Project number:** 5R21AI156583-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Lisa Forbes
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $200,625
- **Award type:** 5
- **Project period:** 2020-12-03 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10311550

## Citation

> US National Institutes of Health, RePORTER application 10311550, Novel Primary Immunodeficiency Disease Due to IL27RA Deficiency (5R21AI156583-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10311550. Licensed CC0.

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