Epithelial proteome profiling suggests essential role of interferon-inducible proteins in allergic rhinitis

• Published in: Journal of allergy and clinical immunology
• Main Authors: Ndika, Joseph, PhD, Airaksinen, Liisa, MD, PhD, Suojalehto, Hille, MD, PhD, Karisola, Piia, PhD, Fyhrquist, Nanna, PhD, Puustinen, Anne, PhD, Alenius, Harri, PhD
• Format: Journal Article
• Language: English
• Published: 2017
• Subjects: Allergy and Immunology; interferon 1 signaling; Allergic-Fall; CF; Seasonal allergic rhinitis; proteomics; SAR; AF; biomarkers; MS; liquid chromatography tandem-mass spectrometry; label free quantification; nasal epithelia; Allergic-Spring; CS; LC-MS/MS; AS; Control-Fall; FDR; Control-Spring; LFQ; mass spectrometry; false discovery rate
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2017.05.040

Abstract Background Seasonal allergic rhinitis (SAR) as a result of intermittent exposure to seasonal pollen, causes itching, nasal congestion and repeated sneezing, with profound effects on the quality of life, work productivity and school performance. While both the genotype and environmental factors may contribute to the immunological basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear. Methods To address these questions, nasal epithelial brushings were collected from 29 SAR and 31 Control individuals during and after the pollen season. We then implemented an orbitrap-based, bottom up label free quantitative proteomics approach, followed by multivariate analyses to identify differentially abundant proteins between the four sample groups. Results We identified a total of 133 differentially abundant proteins for which the most significantly overrepresented functional category was found to be interferon 1 signaling. Two proteins, CST1 and PRNT3, of which the former protects against protease activity of allergens and the latter has a role in epithelial barrier function, were differentially abundant in SAR and Control individuals irrespective of season. Moreover, IFIT1, CST1 and IFIT3 were found to be differentially regulated between SAR and Control individuals, with inverse abundance dynamics during the transition from fall to spring. Conclusion We identified type 1 interferon regulated proteins as biomarkers in SAR, potentially playing an important role in its pathogenesis. Moreover, when compared to SAR patients, healthy individuals exhibit an antagonistic proteome response across seasons, which may yet prove to be a therapeutic target for disease prevention.