How Cystic Fibrosis Affects the Immune System from Birth
Despite significant advances in medication, cystic fibrosis (CF) often results in irreversible lung damage. A recent study by researchers at the Technical University of Munich (TUM), in collaboration with an international team, has revealed that CF introduces immune system changes early in life, possibly even at birth. These alterations lead to persistent inflammation that is not addressed by current treatments targeting mucus production.
The Root Cause of Cystic Fibrosis
Cystic fibrosis is caused by inherited genetic mutations that impair or stop the secretion of the CFTR protein. The respiratory system is particularly vulnerable, with thick and sticky mucus making it difficult to expel bacteria through coughing. This leads to a relentless cycle of infection and inflammation.
Emerging Treatments and Ongoing Challenges
In recent years, doctors have been utilizing CFTR modulator therapies to improve the function of the CFTR protein. These treatments reduce mucus formation and enhance the quality of life for patients. However, studies show that airway inflammation remains a persistent problem, and lung function continues to decline in older individuals.
Current research is focused on uncovering additional mechanisms associated with cystic fibrosis. “Our study aimed to understand how the immune system behaves in cystic fibrosis before the cycle of infection and inflammation sets in,” explained Prof. Nikolai Klymiuk from TUM. His team recently published their findings in Science Translational Medicine.
Immature Immune Cells Identified in Early Life
The researchers analyzed blood samples from children with cystic fibrosis and examined biological material from genetically similar pigs. They discovered that certain innate immune cells in children with CF were immature, making them less effective at combating bacteria. Additionally, at birth, pigs with CF exhibited an increased number and altered composition of immune cells in their lungs. The similarity between the immune systems of pigs and humans suggests these findings are relevant to humans.
Potential “Emergency Program” in CF
One hypothesis for the immune system changes in cystic fibrosis is an “emergency program,” which triggers the body to produce excessive numbers of immune cells. This rapid cell production can lead to the presence of immature, ineffective immune cells that contribute to the cycle of infections and inflammation.
Interestingly, these immune cells typically produce minimal CFTR, indicating that the impact of CF on the immune system is likely indirect. This explains why the new CFTR modulator therapies have limited effectiveness in treating defective immune reactions.
Immune Alterations Are Early Onset
The study found that the immune system changes in cystic fibrosis occur early in life and persist throughout the patient’s lifespan. Prior to this research, abnormal immune cells in adults with CF were thought to be a consequence of repeated infections.
To enable people with cystic fibrosis to live without symptoms, we probably need to tackle the disease on several levels. We hope our work will help us better understand the causes of the defective immune system and correct them in the future.
Nikolai Klymiuk, Professor of Cardiovascular Translation in Large Animal Models
Implications and Future Directions
The findings have significant implications for the management and treatment of cystic fibrosis. By targeting early immune system changes, it may be possible to prevent the chronic inflammation and lung damage associated with CF. This multi-faceted approach could lead to more effective therapies and improved outcomes for patients.
Call to Action
As researchers continue to explore new avenues in cystic fibrosis treatment, the need for public awareness and support remains crucial. Share your thoughts and experiences with cystic fibrosis in the comments below. Join the conversation and stay updated by subscribing to our newsletter. Help drive progress in cystic fibrosis research and advocate for better treatments.