Long-term prognosis of cystic fibrosis (CF) can be anticipated by analyzing a set of 10 genes related to immune response, researchers at National Jewish Health say.
These findings were reported in the journal Annals of the American Thoracic Society, in an article titled “Whole Blood Gene Expression Profiling Predicts Severe Morbidity and Mortality in Cystic Fibrosis: A 5-year Follow-Up Study.”
Most CF patients die due to respiratory failure caused by repeated bacterial infections that damage the lungs.
So, researchers looked at the gene profile of CF patients to find early indicators of patients’ responses to treatment for disease exacerbations resulting from respiratory infections. They also tried to find a link between patients’ response and long-term outcomes.
The genetic profiles of the CF patients analyzed during exacerbation were divided into four groups according to several measures of disease activity and progression.
In group 1, time to next exacerbation was 291 days and none of the patients suffered from major illness events or death.
Group 4 was characterized by a shorter time to the next exacerbation (73 days), compared to the other groups. It also showed more severe exacerbations and more intense infections. Ninety-two percent of the patients belonging to this group had major illness events or death.
The team identified 10 genes as early indicators of patients’ response to treatment for disease exacerbations.
Patients in group 4 presented a higher expression of genes involved in the activation of the innate immune response, the first line of defense against infections. In contrast, the gene profile in group 1 revealed a greater expression of genes linked to the adaptive immune response, which is highly specific to particular pathogens.
Prognosis was measured using the FEV1 parameter (the amount of air a person can expel in one second, a measure of lung function) and exacerbations in the previous year. Interestingly, the 10-gene panel proved to be more sensitive for prognosis prediction than these two tests, allowing the distinction between patients with similar lung function or exacerbation history.
“FEV1 and exacerbation history tell us about a patient’s disease history and existing lung damage,” Milene Saavedra, MD, said in a press release. Saaverda is associate professor of medicine at National Jewish Health and lead author of the study. “The gene panel tells us more about a patient’s biological response to infection, which provided valuable information about the future course of the disease.”
“By looking at the underlying biology of the immune response, this panel allows us to identify subsets of cystic fibrosis patients who are likely to do better or worse in the long term. This information can help guide our treatment plans, so we deliver the best outcomes for our patients,” Saavedra said. “We would presumably treat Cluster 4 patients more aggressively, trading potential side effects for more effective control of damaging infections.”
The National Jewish Health has applied for a patent on this 10-gene panel.
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