Study Identifies Sex-Specific Gene Expression Patterns Linked to Total IgE in Asthma

A research team from the Celedón Lab for Pediatric Asthma Research in the Division of Pediatric Pulmonary Medicine at UPMC Children's Hospital of Pittsburgh published new findings showing that gene activity in the airway differs between boys and girls in ways that may help explain why asthma affects the two sexes differently. The study was published with an accompanying editorial in the Journal of Allergy and Clinical Immunology.

Molin Yue, PhD, from the Department of Biostatistics and Health Data Science at the University of Pittsburgh School of Public Health, was the study's lead author. Juan C. Celedón, MD, DrPH, ATSF, chief, Division of Pediatric Pulmonary Medicine at UPMC Children's, was the senior author. Also contributing to the study from the Celedón Lab were Yueh-Ying Han, PhD, and Wei Chen, PhD. Additional contributors included Yidan Sun, Elin T. G. Kersten, Judith M. Vonk, PhD, and Gerard H. Koppelman, MD, PhD, University of Groningen; Glorisa Canino, PhD, University of Puerto Rico; and Erick Forno, MD, MPH, University of Indiana School of Medicine.

Study Overview and Highlights

Asthma affects boys and girls differently. Before puberty, asthma is more common and more severe in boys. After puberty, the pattern flips, with adult women carrying a higher burden of the disease. Total IgE, a blood marker tied to allergic asthma, also varies by sex and age. Why these differences exist, and how they relate to what is happening in the airway itself, has not been well understood.

To look at this question, the research team used a transcriptome-wide association study, an approach that measures the activity of thousands of genes at once, in nasal epithelial cells. They analyzed samples from two groups of adolescents: 398 Puerto Rican youths ages 12 to 20 years and 303 Dutch youths age 16 years.

Dr. Yue and colleagues found that 406 genes showed significantly different expression levels in girls compared with boys: 225 were more active in girls and 181 were more active in boys. Many of these genes were involved in hormone signaling and immune function. An important finding was that for several of these genes, the relationship between gene activity and total IgE level was not the same in boys and girls. The same IgE level was associated with different patterns of gene activity in girls than in boys.

Additionally, the study found that girls had higher activity in pathways involved in building proteins, while boys had higher activity in immune pathways, including interferon signaling. Nineteen additional pathways, including those involved in immune signaling and inflammation, also behaved differently in boys and girls depending on IgE level.

Clinical Significance

The findings may help explain why asthma does not look the same in boys and girls and why the disease shifts around puberty. The research also strengthens the case for treating sex as a meaningful biological variable in asthma research, rather than something to be adjusted for in the background. If the airway responds to allergic signals differently in boys and girls, treatments that work well in one group may not work as well in the other. The specific genes and pathways identified in this study may eventually point toward more tailored asthma treatments designed around a patient's sex and IgE profile rather than a one-size-fits-all approach.

Learn more about the Division of Pediatric Pulmonary Medicine at UPMC Children's Hospital of Pittsburgh.

Study Reference

Yue M, Sun Y, Han YY, Canino G, Forno E, Vonk JM, Kersten ETG, Chen W, Koppelman GH, Celedón JC. Transcriptome-wide association study of sex effects identifies sex-specific nasal epithelial gene expression profiles for total IgE. J Allergy Clin Immunol. 2026 May; 157(5): 1043-1051.

Editorial Reference

Tada Y, Kamata M. Internalizing sex differences in allergic diseases: a sex-dependent airway epithelial immune network. J Allergy Clin Immunol. 2026 May; 157(5):1028-1030.