Dual-Compartment Proteomic analysis reveals inflammatory signatures of sleep disturbance in allergic rhinitis

Int Arch Allergy Immunol. 2026 Oct 7:1. doi: 10.1159/iaa/adfag031. Online ahead of print.

ABSTRACT

Introduction Allergic rhinitis (AR) is often accompanied by sleep disturbance, while the molecular mechanisms underlying sleep-related exacerbation of nasal symptoms remain poorly understood. This study aimed to investigate the inflammatory protein signatures associated with poor sleep in AR using a dual-compartment proteomic approach. Methods We first analyzed 3,731 adult participants from the 2005-2006 National Health and Nutrition Examination Survey (NHANES) cycle to validate the association between sleep duration and AR. We then enrolled 40 AR patients (20 poor sleepers, Pittsburgh Sleep Quality Index [PSQI] > 5; 20 normal sleepers, PSQI ≤ 5) and performed Olink proteomic profiling in paired serum and nasal secretion (NS) samples. Differential expression analysis, functional enrichment, cross-compartment correlation, Least Absolute Shrinkage and Selection Operator (LASSO) regression, receiver operating characteristic (ROC) analysis, and sequential multivariable linear regression were conducted. Results In NHANES, short sleep duration (<6 h) was significantly associated with increased odds ratio (OR) of AR (OR = 1.27, 95% confidence interval [CI] 1.05-1.54, P = 0.013) and elevated serum total immunoglobulin E (IgE). In the clinical cohort, poor sleepers had higher Total Nasal Symptom Score (TNSS) (P < 0.001), Multidimensional Fatigue Inventory (MFI) (P < 0.001), and blood eosinophil counts (P = 0.011). Proteomics identified 27 serum and 20 NS differentially expressed proteins (DEPs), with 9 overlapping DEPs enriched in interleukin-17 (IL-17), tumor necrosis factor (TNF), and chemokine signaling pathways. A four-marker panel (serum beta-nerve growth factor [β-NGF], serum transforming growth factor-beta 1 [TGF-β1], NS interleukin-8 [IL-8], NS matrix metalloproteinase-1 [MMP-1]) achieved an area under the curve (AUC) of 0.88 (95% CI 0.76-0.97, P < 0.001) for distinguishing poor from normal sleepers. Cross-compartment correlation analysis revealed significant serum-NS protein concordance, consistent with systemic-local inflammatory crosstalk. Sequential multivariable regression showed that serum β-NGF independently predicted TNSS severity even after PSQI adjustment (β = 2.22, P = 0.044), whereas nasal IL-8 was fully attenuated (β = 0.58, P = 0.391). Conclusion Poor sleep is associated with exacerbated AR through coordinated systemic and local inflammatory responses. Serum β-NGF is independently associated with nasal symptoms, whereas the association of NS IL-8 with symptoms appears to be explained by sleep disturbance. Integrating markers from both compartments enhances the identification of AR patients with poor sleep.

PMID:42842521 | DOI:10.1159/iaa/adfag031