A study indicates pediatric asthma patients with a common gene variant may experience diminished response to mepolizumab during viral infections.
RT’s Three Key Takeaways:
- High Genetic Prevalence: A variant in the SERPINE1 gene, found in approximately 60% of the population, may cause children to be less responsive to the asthma biologic mepolizumab.
- Airway Inflammation Mechanism: The genetic variant produces elevated levels of the protein plasminogen activator inhibitor 1 during viral respiratory illnesses, stimulating inflammatory pathways that damage airway lining when paired with the drug.
- Advance for Precision Healthcare: Pre-identifying genetic differences in pediatric asthma patients could guide clinicians in selecting alternative, more effective therapeutic regimens earlier.
Asthmatic children with a variant in the SERPINE1 gene—a trait present in 60% of the general population—may experience reduced responsiveness to mepolizumab, an asthma biologic prescribed to treat severe flare-ups, according to a study published in the Journal of Allergy and Clinical Immunology.
Researchers found that this specific genetic alteration produces elevated levels of the protein plasminogen activator inhibitor 1 (PAI1) during viral illness, leading to increased airway scarring and an impaired antiviral defense. When mepolizumab is administered in the presence of this variant, additional inflammatory pathways that damage airway tissue are activated, whereas these adverse cellular changes are absent in children who lack the SERPINE1 variant.
“We know from previous studies that children with this genetic variant are more likely to have asthma exacerbations during a viral illness, and now we have greater understanding of how that happens,” said Rajesh Kumar, MD, interim division head of allergy and clinical immunology at Ann & Robert H. Lurie Children’s Hospital of Chicago and professor of pediatrics at Northwestern University Feinberg School of Medicine, in a news release.
Investigating Airway Pathways and Precision Medicine
To evaluate these cellular dynamics, investigators analyzed clinical data, health records, and nasal samples gathered from pediatric participants aged 6 to 17 years who were prone to frequent asthma exacerbations.
Dr Kumar cautioned that the investigation evaluated biological mechanisms within the airway lining during viral infections rather than definitive clinical endpoints, as the trial cohort was not statistical powered to confirm direct clinical outcomes. Even so, based on the behavior of these inflammatory pathways, investigators noted that carrying the SERPINE1 variant could correlate with reduced clinical effectiveness of mepolizumab.
“Our findings also may lead to future studies to help identify patients for whom treatment with mepolizumab may not be as effective and who may even have more of other types of inflammation that the drug does not block,” said Kumar, senior author of the study, in a news release. “This is important to know in advance so the best therapeutic options could be considered earlier for these children. We are paving the way for precision medicine in pediatric asthma.”
Implications for Pediatric Respiratory Care
The findings point toward an expanding role for genetic profiling in pediatric respiratory healthcare, particularly when standard biologic interventions fail to suppress flare-ups triggered by viral infections.
“Our study implies that during a viral illness, children with asthma who have the genetic variant may have more inflammation from the airway lining during viral illness compared to children without the variant, and this genetic difference creates distinct responses to mepolizumab,” said Kumar. “These insights bring us closer to being able to treat asthma according to each child’s individual genetic makeup. We are very excited about the enormous potential of precision medicine to improve asthma outcomes for children.”
