Common SERPINE1 Variant Changes Airway Response to Mepolizumab in Children

Molecular data show the variant raises PAI‑1 and fibrosis‑linked gene activity during viral illness, requiring clinical trials to test whether this alters treatment benefit.

Overview

A peer‑reviewed Journal of Allergy and Clinical Immunology study published Thursday analyzed nasal‑lavage RNA from two pediatric cohorts to test how a SERPINE1 promoter polymorphism affects airway biology and drug response.
The SERPINE1 promoter variant (rs1799768, called 4G/5G) is common in the U.S. cohorts studied—about 60% carry at least one risk allele—and prior work links it to roughly a 2.6‑fold higher risk of severe asthma exacerbations.
During viral respiratory illness children with the risk allele produced more plasminogen activator inhibitor‑1 (PAI‑1), a protein associated with airway scarring and weaker antiviral signaling.
The study found a gene‑by‑drug interaction with mepolizumab in risk‑allele carriers marked by higher TGF‑β/SMAD3 and squamous‑epithelium gene activity, a molecular pattern that could reduce or alter drug benefit but was not linked to clinical outcomes in this analysis.
Researchers say the results point toward possible genotype‑informed treatment choices for exacerbation‑prone children but emphasize that prospective, genotype‑stratified clinical trials are needed before changing prescribing practice.