GDNF, IL-18R1, IL-15RA Identified as Novel Biomarkers in Seasonal Allergic Rhinitis

New research identified key inflammation-related proteins associated with seasonal allergic rhinitis, including glial cell line-derived neurotrophic factor (GDNF), interleukin-18 receptor 1 (IL-18R1), and interleukin-15 receptor alpha (IL-15RA).1

“…GDNF, IL-18R1, and IL-15RA emerged as central biomarkers due to their strong seasonal fluctuations and associations with multiple nasal symptoms,” wrote investigators, led by Jiaqi Shen, from Zhejiang Provincial People’s Hospital at Hangzhou Medical College, People’s Republic of China. “GDNF, a member of the GDNF family ligands (GFLs), emerged as a novel candidate biomarker in our study.”

Urbanization and industrialization in recent decades have contributed to the uptick in seasonal allergic rhinitis cases. Research suggests that toxic substances in laundry and dishwasher detergents, shampoos, and toothpastes—as well as microplastics in packaged food and air pollution—damage the epithelium of skin, lungs, and the gastrointestinal system.2

The rise in seasonal allergic rhinitis prevalence underscores the need for targeted diagnostic and therapeutic interventions. However, the pathogenesis of seasonal allergic rhinitis remains poorly understood, particularly regarding immune regulation and the molecular mechanisms underlying symptom exacerbation.

Investigators sought to identify key inflammation-related proteins and specific molecular pathways associated with seasonal allergic rhinitis to help inform potential therapeutic targets.1 They also explored the links between differentially expressed proteins and seasonal allergic rhinitis symptoms, such as sneezing, rhinorrhea, nasal blockage, itchy nose, and itchy eyes.

Shen and colleagues collected serum samples from 19 patients (median age, 31 years; 52.6% males; median body mass index, 23.8 kg/m2) with seasonal allergic rhinitis during both allergy and non-allergy seasons. Participants had a median total IgE level of 430.4 IU/mL (IQR: 226.7–722.1).

The team identified differentially expressed proteins using the Olink Target 96 Inflammation panel. These proteins were further analyzed through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses; a Spearman correlation analysis was used to explore the link between the proteins and seasonal allergic rhinitis symptoms.

“Olink proteomic technology was employed for the first time to investigate inflammation-related protein changes in SAR patients across allergy seasons,” investigators explained in their paper. “This approach enabled the identification of 36 DEPs that correlated with disease activity.”

The study identified 36 inflammation-related, differentially expressed proteins, all upregulated during the allergy season. The proteins of GDNF, IL-18R1, and IL-15RA demonstrated a strong correlation with seasonal allergic rhinitis symptoms.

Investigators also found that sneezing was linked to IL-2 receptor beta (IL-2RB) (P = .013), rhinorrhea with FMS-related tyrosine kinase 3 ligand (Flt3L) (P = 0.004), and nasal blockage with osteoprotegerin (OPG) (P = 0.002). Proteins significantly associated with ≥ 2 nasal symptoms included GDNF, Flt3L, IL-18R1, CCL25, IL-2RB, leukemia inhibitory factor receptor (LIF-R), colony-stimulating factor 2 (CSF-2), and IL-15RA.

Enrichment analyses showed these proteins are involved in critical pathways with Ras signaling and small GTPases. Another analysis showed immune-related pathways with PI3K-Akt signaling and cytokine-cytokine receptor interactions.

The study also identified the top 9 proteins with the most statistically significant changes from in allergy season to out-of-allergy season: DNF, IL-18R1, IL-15RA, colony-stimulating factor-1 (CSF-1), interleukin-7 (IL-7), leukemia inhibitory factor receptor (LIF-R), Flt3L, STAM-binding protein (STAMBP), CUB domain-containing protein 1 (CDCP1), and adenosine deaminase (ADA)

The novel proteins discovered—GDNF, IL-18R1, and IL-15RA—ultimately expand the biomarker panel for diagnosing and monitoring seasonal allergic rhinitis.

“Although the function of GDNF in [seasonal allergic rhinitis] research remains underexplored, our findings suggested that it might play a critical role in symptom development, offering a promising direction for future [seasonal allergic rhinitis] research,” investigators wrote.

References

1. Shen J, Zheng X, Yan M, et al. Seasonal Proteomic Variations and Biomarkers in Seasonal Allergic Rhinitis: Insights from Olink Inflammation Profiling. J Inflamm Res. 2025;18:6191-6202. Published 2025 May 12. doi:10.2147/JIR.S519126

2. Ozdemir C, Kucuksezer UC, Ogulur I, Pat Y, Yazici D, Ardicli S, Akdis M, Nadeau K, Akdis CA. Lifestyle Changes and Industrialization in the Development of Allergic Diseases. Curr Allergy Asthma Rep. 2024 Jul;24(7):331-345. doi: 10.1007/s11882-024-01149-7. Epub 2024 Jun 17. PMID: 38884832; PMCID: PMC11233349.