Recent research identified a gene that modifies the severity of lung disease in people with cystic fibrosis (CF). The findings open the door to possible new targets for treatment says the research team from Wake Forest University Baptist Medical Center, Winston-Salem, NC, and others. This is the first published study to search the entire genome looking for genes that modify the severity of CF.

“This is a good example of researchers with different expertise coming together and using the knowledge gained from mapping the human genome to make discoveries that improve our understanding of cystic fibrosis,” says co-author Carl Langefeld, PhD. “It may also help in the identification of targets for drug development and the development of tools for the earlier diagnosis of individuals with cystic fibrosis who are susceptible to severe lung disease.”

After analyzing the genetic makeup of nearly 3,000 patients with CF, researchers found that small genetic differences in a gene called IFRD1 correlate with lung disease severity. While probing how the gene might alter the disease’s course, researchers discovered the protein encoded by IFRD1 is particularly abundant in a type of white blood cell called neutrophils, and that it regulates their function. Part of the immune system, neutrophils are known to cause inflammatory damage to the airways of people with CF.

“Neutrophils appear to be particularly bad actors in cystic fibrosis,” says senior investigator Christopher Karp, MD, the director of Molecular Immunology at Cincinnati Children’s Hospital Medical Center. “They are important to the immune system’s response to bacterial infection. In cystic fibrosis, however, neutrophilic airway inflammation is dysregulated, eventually destroying the lung.”

The researchers also determined that IFRD1’s regulation of neutrophil function depends on its interaction with histone deacetylases – enzymes important for regulating gene transcription. Additional research is needed to better understand this interaction before its potential role for treatment is known.

“It’s possible that IFRD1 itself could become a target for treatment, but right now it’s a signpost to pathways for further study,” says Karp. “We want to find out what other genes and proteins IFRD1 interacts with, and how this is connected to inflammation in cystic fibrosis lung disease.”

The study is published in Nature.