Peripheral effector-memory CD4⁺ T cells reflect clinical symptom burden in pediatric allergic rhinitis

Pediatric allergic rhinitis (AR) can substantially affect quality of life and school performance, yet conventional sensitization markers such as allergen-specific immunoglobulin E (sIgE) do not consistently reflect symptom severity. We examined whether activation-induced marker (AIM)-defined allergen-specific peripheral effector-memory CD4⁺ T-cell (peff-mCD4) frequencies were associated with symptom burden.

In this pilot, single-center observational study, house dust mite (HDM)-specific responses were analyzed in 20 children and Japanese cedar pollen (JCP)-specific responses in 19. Nasal symptom numerical rating scale (NRS) and total nasal symptom score (TNSS) were recorded. Peff-mCD4 cells were quantified as CD154⁺CD137⁺ cells within memory CD4⁺ T cells after short-term ex vivo allergen stimulation.

Peff-mCD4 frequency was strongly associated with NRS and TNSS in both the HDM-specific (Spearman ρ = 0.882 and 0.835, respectively) and JCP-specific analyses (ρ = 0.828 and 0.769, respectively; all q < 0.001). In contrast, sIgE showed weaker associations with symptom scores, and none of the four sIgE-symptom associations remained significant after FDR adjustment. These peff-mCD4 associations remained significant after adjustment for age and sex. In exploratory ROC analyses using TNSS ≥8 as an operational threshold, peff-mCD4 yielded AUCs of 0.867 for HDM and 0.910 for JCP.

Peff-mCD4 frequency was strongly associated with symptom burden in pediatric AR. Larger longitudinal and externally validated studies are required to determine its potential utility as a peripheral blood cellular correlate of clinical symptom burden.