Children with a common genetic variant may have more inflammation in response to an asthma drug

by Ann & Robert H. Lurie Children's Hospital of Chicago

edited by Gaby Clark, reviewed by Andrew Zinin

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Children with a variant in the SERPINE1 gene—which is found in 60% of the population—may be less responsive to mepolizumab, a drug used to treat asthma flares, according to a study published in the Journal of Allergy and Clinical Immunology.

The study found that this genetic variant leads to increased production of a protein (PAI1) during a viral illness, resulting in more airway scarring and a weaker antiviral response. When patients with the variant receive mepolizumab, the drug stimulates additional inflammatory pathways that damage the airway. Those changes do not occur in patients without the 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 a greater understanding of how that happens," said senior author Rajesh Kumar, M.D., 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.

"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 inflammation of types that the drug does not block," he said. "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."

For this study, Kumar and colleagues analyzed data and nasal samples from children ages 6 to 17 with exacerbation-prone asthma who had participated in previous studies.

Kumar cautioned that the results show what happens in the airways of patients with the SERPINE1 variant during a viral illness and in response to mepolizumab, rather than what would be seen clinically. The study was not large enough to support a clinical conclusion. However, based on how these inflammatory pathways function, he would expect that children with asthma who have the variant could have worse asthma outcomes with mepolizumab.

"Our study implies that during a viral illness, children with asthma who have the genetic variant may have more inflammation in the airway lining than children without the variant, and this genetic difference creates distinct responses to mepolizumab," Kumar said. "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."

Publication details

Journal of Allergy and Clinical Immunology (2026).

Journal information: Journal of Allergy and Clinical Immunology

Key medical concepts

mepolizumabAsthmaPlasminogen Activator Inhibitor 1

Clinical categories

Allergy and immunologyPediatricsChildren's healthClinical geneticsCommon illnesses & Prevention Provided by Ann & Robert H. Lurie Children's Hospital of Chicago Who's behind this story?

Gaby Clark

MA in English, copy editor since 2021 with experience in higher education and health content. Dedicated to trustworthy science news. Full profile →

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