IGF2R Blood Levels May Help Predict Antibiotic Response in CF Pulmonary Exacerbations, Study Says

Measuring the levels of insulin-like growth factor 2 receptor (IGF2R) during the first days of treatment with intravenous antibiotics could help predict treatment response in cystic fibrosis patients experiencing pulmonary exacerbations, a study has found.

The study, “Identification of novel blood biomarkers of treatment response in cystic fibrosis pulmonary exacerbations by label-free quantitative proteomics,” was published in the journal Nature Scientific Reports.

Pulmonary exacerbations are frequent among people with cystic fibrosis (CF). They are commonly caused by viral and bacterial infections, but can also result from exposure to non-infectious factors, such as polluted air. The most common treatment is intravenous antibiotics, but sometimes patients do not respond well and can experience irreversible loss of lung function.

Therefore, identifying novel biomarkers that help assess if a patient is responding to a combination of antibiotics in the first days of treatment could help improve the patient’s overall response and outcome.

Researchers at the University of British Columbia, in Vancouver, Canada, assessed the levels of several blood proteins to identify potential predictive biomarkers of treatment response in people with CF who received intravenous antibiotics to treat pulmonary exacerbations.

The study included 22 participants, and measured protein changes during 25 pulmonary exacerbations that required hospitalization and treatment with intravenous antibiotics. Blood samples were taken from patients at the time of admission, after five and 10 days of treatment with intravenous antibiotics, and at the end of treatment.

Results showed that most participants recovered to 90% of their baseline lung function after the treatment, and 60% of the 25 pulmonary exacerbations achieved a clinically-meaningful response, assessed by a decrease in CFRSD-CRISS scores.

The investigators evaluated the changes in 346 proteins, and found that the levels of 47 of them changed considerably during the first five days of treatment. These included proteins involved in immune response and inflammation, such as interleukin-6, C-reactive protein, and calprotectin, which had previously been linked to CF activity.

IGF2R was the only protein whose levels changed considerably during early treatment, and correlated with response to therapy and patient outcomes. Therefore, this protein could serve as an early marker of response to therapy during treatment with intravenous antibiotics, according to the team.

IGF2R regulates several processes such as wound healing, blood vessel growth, and response to viral infections. It has been associated with inflammatory processes in different groups of people, such as HIV-positive individuals, but has not been linked to CF.

“We identified several blood proteins involved in complement activation and inflammatory/immune-related pathways that changed in response to [intravenous] antibiotic treatment. Early change in IGF2R correlated with symptom improvement by the end of treatment, and requires further validation as an early marker of symptomatic treatment response in individuals with CF,” the researchers said.

The team also noted that future studies, including more patients, should validate the findings, and assess other potential biomarkers.