title: Nasal mucus proteomic changes reflect altered immune responses and epithelial permeability in patients with allergic rhinitis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: ENT-University Hospital, Medical University of Graz, Graz, Austria. Electronic address: peter.tomazic@medunigraz.at.
authors.forename: Peter Valentin
authors.initials: PV
authors.lastname: Tomazic
authors.affiliation: Institute of Pathology, Medical University of Graz, Graz, Austria; Center of Medical Research, Mass Spectrometry Core Facility, Medical University of Graz, Graz, Austria; Austrian Center of Industrial Biotechnology, Graz, Austria; Omics Center Graz, Graz, Austria. Electronic address: ruth.birner-gruenberger@medunigraz.at.
authors.forename: Ruth
authors.initials: R
authors.lastname: Birner-Gruenberger
authors.affiliation: ENT-University Hospital, Medical University of Graz, Graz, Austria.
authors.forename: Anita
authors.initials: A
authors.lastname: Leitner
authors.affiliation: Center of Medical Research, Mass Spectrometry Core Facility, Medical University of Graz, Graz, Austria; Austrian Center of Industrial Biotechnology, Graz, Austria; Omics Center Graz, Graz, Austria.
authors.forename: Britta
authors.initials: B
authors.lastname: Obrist
authors.affiliation: Center of Medical Research, Mass Spectrometry Core Facility, Medical University of Graz, Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Spoerk
authors.affiliation: ENT-University Hospital, Medical University of Graz, Graz, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Lang-Loidolt
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000032:analysis; D016633:Apolipoprotein A-II / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000737:chemistry* / Q000276:immunology; D010539:Permeability; D040901:Proteomics / Q000379:methods*; D065631:Rhinitis, Allergic; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology* / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: C505693:APOA1 protein, human; C115794:APOA2 protein, human; D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D003176:Complement C3; D000511:alpha-Macroglobulins
keywords: Nasal mucus; allergic rhinitis; mass spectrometry; proteome; proteomics