Influence of genetic polymorphisms on omalizumab clinical response in pediatric severe asthma: a pilot study

Introduction – Severe asthma affects 3%–5% of children and may remain uncontrolled despite high-dose inhaled corticosteroids and other controller therapies. Omalizumab, an anti-IgE monoclonal antibody, is approved for children ≥6 years with severe asthma, however treatment response shows substantial interindividual variability. Objectives – This study aimed to investigate whether selected single nucleotide polymorphisms (SNPs) in genes involved in IgE signaling and immune regulation are associated with clinical response to omalizumab in pediatric severe asthma. Methods – In this retrospective cohort study, 30 children with severe asthma treated with omalizumab for 12 months were genotyped for selected SNPs in FCER1B, FCGR2A, FCGR3A, C3, and GATA2 genes. Clinical response was defined as: (i) ≥10% improvement in FEV1%, (ii) ≥50% reduction or absence of asthma exacerbations, and (iii) ≥50% reduction or discontinuation of oral corticosteroids (OCS). A combined response was defined as meeting at least two of these outcomes. Changes in GINA step were also assessed separately. Results – FEV1% improvement showed a nominal association with the variant allele of GATA2 rs4857855 (p = 0.044). Reduction in exacerbation was nominally associated to variant alleles of FCER1B rs573790 (p = 0.003), and GATA2 rs4857855 (p = 0.032). OCS reduction was nominally associated with variant alleles of FCER1B rs573790 (p = 0.037) and FCGR3A rs396991 (p = 0.014). A combined response was nominally associated with FCER1B rs573790 and GATA2 rs4857855 variant alleles (p = 0.012). No SNP was associated with all three outcomes or GINA step reduction. Conclusion – Genetic variability in IgE- and Fc receptor–related pathways may contribute to differential response to omalizumab in children with severe asthma. These findings are exploratory and require validation in larger prospective studies.