Study Pinpoints New Gene for Cysti...(CF looking for markers that segregated w...),Health

IFRD1 is a transcription factor, a protein that regulates the expression of other genes. Karp said they found that the gene is highly expressed in neutrophils, and that neutrophils from mice that lack IFRD1 are less adept at carrying out their antibacterial activities, both in cultures and in animals. Yet at the same time, these mice also suffer less airway damage, weight loss and inflammation from those infections.

"Since we think in the CF airway that neutrophils are basically double-edged swords, and do help against infection but over time destroy the airway, it's a profoundly interesting phenotype," Karp said.

But that's in mice. Does IFRD1 status affect neutrophil function in humans, too?

By assaying human neutrophils, Karp found that in fact it does. That, says Karp, "[closes] the circle, basically."

Thus, the data suggest that subtle variations in the IFRD1 gene modulate neutrophil activity, which can in turn temper the degree of lung damage these cells cause in CF airways.

"This is an interesting finding that might explain why some CF patients have more severe lung deterioration than matched CF [patients] with the same [CFTR] genotype," said Dr. Robert Giusti, director of the Cystic Fibrosis Center at the Long Island College Hospital in Brooklyn, N.Y.

Giusti said the study could eventually pave the way to altered CF management.

"We might be able, by testing for the presence of these modifier genes, to alter our therapy and be more aggressive in the face of a lot of inflammation," he said. "And if we know that a patient is predisposed to inflammation, we can start early on with anti-inflammatory therapy and that might, therefore, limit the degree of lung disease."