With support from the Rheumatology Research Foundation’s Career Development Bridge Funding: R Bridge award, Dr. Pui Lee’s research uncovered key immune system pathways involved in deficiency of adenosine deaminase 2 (DADA2) and is helping pave the way for more personalized treatments in the future.
The Problem:
Deficiency of adenosine deaminase 2 (DADA2) is a rare genetic disease that can cause serious inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... throughout the body. Because the disease was only discovered in 2014, doctors are still learning why it affects people so differently.
Patients with DADA2 can experience very different symptoms. Some develop blood vessel inflammation (vasculitis), early-onset strokes, skin rashes (livedo racemosa) , and recurring fevers, while others experience serious blood and bone marrow problems. In severe cases, the disease can become life-threatening.
Researchers still do not fully understand what drives these different systems. Without understanding the underlying causes of these different disease patterns, it is difficult for doctors to predict how the disease will progress or determine which treatments may work best for each patient.
How Dr. Lee’s Project Addressed the Problem:
The research team:
- Studied how abnormal ADA2 protein may activate immune cells called monocytes and trigger inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... through increased tumor necrosis factor (TNF) production
- Investigated how the absence of ADA2 protein may affect healthy blood cell production in the bone marrow
- Worked to explain why some patients develop severe blood vessel inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... while others develop bone marrow failure
- Aimed to improve understanding of DADA2 in order to support the development of more personalized treatments for different patient groups
- Explored broader mechanisms of blood vessel inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... that may also apply to other inflammatoryInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... diseases
The Impact of this Research:
- Improved understanding of how DADA2 causes inflammation and affects patients differently Identified important immune system signals linked to different forms of DADA2, which may lead to more personalized treatments in the future
- Supported the development of new laboratory models that will help scientists continue studying DADA2 and potential therapies
- Strengthened collaborations among experts in rheumatology, immunology, and computational biology
- Established a patient sample biobank to support future research and accelerate discoveries
This research may also improve understanding of inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... in other rheumatic and inflammatory diseases, potentially leading to more targeted treatments and better patient care in the future.