Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 3; pp. 741 - 750
• Main Authors: Tomazic, Peter Valentin, MD, Birner-Gruenberger, Ruth, PhD, Leitner, Anita, Obrist, Britta, BSc, Spoerk, Stefan, Lang-Loidolt, Doris, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.03.2014; Elsevier; Elsevier Limited
• Subjects: Adult; allergic rhinitis; Allergies; Allergy and Immunology; alpha-Macroglobulins - analysis; Apolipoprotein A-I - analysis; Apolipoprotein A-II - analysis; Biological and medical sciences; Biotechnology; Children & youth; Complement C3 - analysis; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunopathology; Laboratories; Male; mass spectrometry; Medical sciences; Metabolism; Metabolites; Middle Aged; Nasal Mucosa - chemistry; Nasal Mucosa - immunology; Nasal mucus; Non tumoral diseases; Nose; Otorhinolaryngology. Stomatology; Permeability; Proteins; proteome; proteomics; Proteomics - methods; Rhinitis, Allergic; Rhinitis, Allergic, Perennial - immunology; Rhinitis, Allergic, Perennial - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Software; Statistical analysis; Tandem Mass Spectrometry; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Complement C5; GRN; SERPINA1; IgJ chain; Complement C3; HP; Apolipoprotein B-100; Vitronectin; BPI fold–containing family A member 1; Spectral count; α1-Antitrypsin; Antileukoproteinase; WFDC2; C3; SC; LC-MS/MS; VTN; BPIFA1; C5; Haptoglobin; mass spectrometry; A2M; Apolipoprotein A-4; APOB; Apolipoprotein A-2; Apolipoprotein A-1; Nasal mucus; α2-Macroglobulin; Lactotransferrin; proteomics; Liquid chromatography–tandem mass spectrometry; APOA2; APOA1; APOA4; Nonsecretory ribonuclease; LYZ; RNASE2; IGJ; proteome; Lysozyme C; Granulin; BPIFB1; SLPI; WAP 4-disulfide core domain protein; allergic rhinitis; BPI fold–containing family B member 1; LTF; Human; Allergy; Immunopathology; Nose disease; Immune response; Rhinitis; Exploration; Proteome; Mucus; Permeability; Immunology; Nose; Proteomics; ENT disease; Mass spectrometry
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.09.040

Background Nasal mucus is the first-line defense barrier against (aero-) allergens. However, its proteome and function have not been clearly investigated. Objective The role of nasal mucus in the pathophysiology of allergic rhinitis was investigated by analyzing its proteome in patients with allergic rhinitis (n = 29) and healthy control subjects (n = 29). Methods Nasal mucus was collected with a suction device, tryptically digested, and analyzed by using liquid chromatography–tandem mass spectrometry. Proteins were identified by searching the SwissProt database and annotated by collecting gene ontology data from databases and existing literature. Gene enrichment analysis was performed by using Cytoscape/BINGO software tools. Proteins were quantified with spectral counting, and selected proteins were confirmed by means of Western blotting. Results In total, 267 proteins were identified, with 20 (7.5%) found exclusively in patients with allergic rhinitis and 25 (9.5%) found exclusively in healthy control subjects. Five proteins were found to be significantly upregulated in patients with allergic rhinitis (apolipoprotein A-2 [APOA2], 9.7-fold; α2-macroglobulin [A2M], 4.5-fold; apolipoprotein A-1 [APOA1], 3.2-fold; α1-antitrypsin [SERPINA1], 2.5-fold; and complement C3 [C3], 2.3-fold) and 5 were found to be downregulated (antileukoproteinase [SLPI], 0.6-fold; WAP 4-disulfide core domain protein [WFDC2], 0.5-fold; haptoglobin [HP], 0.7-fold; IgJ chain [IGJ], 0.7-fold; and Ig hc V-III region BRO, 0.8-fold) compared with levels seen in healthy control subjects. Conclusion The allergic rhinitis mucus proteome shows an enhanced immune response in which apolipoproteins might play an important role. Furthermore, an imbalance between cysteine proteases and antiproteases could be seen, which negatively affects epithelial integrity on exposure to pollen protease activity. This reflects the important role of mucus as the first-line defense barrier against allergens.