A biologic drug used to treat severe asthma may be less effective in children with a common genetic variant, found in 60% of people. The variant is linked to an increased likelihood of severe asthma exacerbations.
Kids who carry a specific version of the SERPINE1 gene showed stronger inflammatory reactions when given mepolizumab, a monoclonal antibody treatment for asthma, than their peers without this genetic variation.
Genetic Variant and Asthma Treatment
According to the study, published in the Journal of Allergy and Clinical Immunology, the genetic variant affects the response to mepolizumab. Rajesh Kumar, MD, senior author from Northwestern University, said: “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.”
The SERPINE1 gene encodes the plasminogen activator inhibitor (PAI)1 protein. A single guanine deletion/insertion at position 2675 in the promoter region of the SERPINE1 gene is associated with a 2.6-fold increased risk of severe asthma exacerbations.
Study Findings
The team, led by Ariel Helms Thames, PhD, examined whether genotype differences in T helper 2 type immune responses might be affected by the interruption of these pathways with mepolizumab. They found that children with the A allele, a proxy for 4G, initially had lower baseline levels of SERPINE1/PAI-1 expression in airway tissues, but produced more than others during viral illness.
The scientists analyzed nasal fluid samples from young asthma patients aged six to 17 using expression quantitative trait locus and gene co-expression network techniques, focusing on children prone to flare-ups.
This research could reshape how asthma is managed in children. Mepolizumab, an anti-interleukin-5 antibody, limits eosinophil production and survival, making it a key therapy for severe, treatment-resistant eosinophilic asthma.
Conclusion of the Study
The authors noted that the finding that those with the AA genotype have lower baseline levels of SERPINE1/PAI-1 gene expression may help explain the widespread persistence of the risk allele in the population. The study’s results pave the way for precision care in pediatric asthma, helping to advance the most effective therapeutic options at the earliest stages.
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