Cellular Signatures of Asthma Persistence: Single-Cell Analysis Provides New Insights into Childhood Asthma

In the fourth part of our series presenting the winners of the poster awards at the DZL Annual Meeting 2025, we highlight the project of Dr. Ruth Grychtol, who works at the Department of Pediatric Pneumology, Allergology and Neonatology at Hannover Medical School (MHH). She was honored by the Disease Spanning Working Group Single Cell Analysis for her scRNAseq study on asthma persistence in children – a project with high relevance for early diagnostics and personalized therapeutic approaches.

Childhood asthma represents a major diagnostic and therapeutic challenge. Asthma-like symptoms such as cough, shortness of breath, or wheezing occur in about one third of all children during the first years of life in connection with viral respiratory infections. However, only a small proportion of these children go on to develop persistent asthma into adolescence or adulthood. Until now, it has been difficult to diagnose children with very early-onset asthma and provide them with targeted treatment.

Within the nationwide All Age Asthma Cohort (ALLIANCE) study, Dr. Grychtol and an interdisciplinary team introduced new approaches to characterizing these patient groups – an achievement that earned her the poster award at the DZL Annual Meeting 2025 in the cross-sectional Working Group Single Cell Analysis.

Using single-cell RNA sequencing (scRNAseq), the team analyzed peripheral blood lymphocytes (PBMCs) from children with early childhood asthma as well as from children who only had infection-associated symptoms in infancy – each with up to ten years of follow-up. The aim was to identify cellular signatures associated with clinical outcomes (persistence vs. remission).

Samples came from well-characterized patient groups with an average age of 3.2 and 9.5 years. After cell sorting and quantitative CITE-Seq labeling, single-cell analysis was performed using the 10x Genomics platform. In total, 28 different cell populations were identified, including classical T-cell subtypes, NK cells, monocytes, and B cells.

Although overall cell frequencies did not differ significantly between persistent asthma and remission, the analysis of differentially expressed genes (DEGs) revealed five cell populations of particular interest: MAIT cells, CD14⁺ monocytes, double-negative T cells, CD56⁺bright NK cells, and intermediate B cells. Each of these showed more than 100 significantly altered genes, pointing to a previously underestimated role in disease persistence.

The ongoing analyses aim to identify regulatory networks and biomarkers that could enable early risk stratification in wheezing toddlers – a potential milestone for personalized prevention and treatment approaches in childhood asthma.

With the awards to Laurien Czichon, Julia Rückoldt, Dr. Jan Fuge, and Dr. Ruth Grychtol, the DZL site BREATH once again demonstrated its broad scientific excellence at this year’s Annual Meeting of the German Center for Lung Research – ranging from cell biological modeling to regeneration research, digital healthcare, and molecular single-cell analysis in large cohorts.

We warmly congratulate all awardees and look forward to the exciting results to come from these innovative projects!

 

Text: BREATH/AB

Photo: MHH/ Tom Figiel

Awardee Dr. Ruth Grychtol, Department of Pediatric Pneumology, Allergology and Neonatology (MHH) and PI at BREATH