title: Identification of novel biomarkers in seasonal allergic rhinitis by combining proteomic, multivariate and pathway analysis.
abstract: BACKGROUND
  Glucocorticoids (GCs) play a key role in the treatment of seasonal allergic rhinitis (SAR). However, some patients show a low response to GC treatment. We hypothesized that proteins that correlated to discrimination between symptomatic high and low responders (HR and LR) to GC treatment might be regulated by GCs and therefore suitable as biomarkers for GC treatment.
  
  
  RESULTS
  We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and performed multivariate analysis to identify a combination of proteins that best separated symptomatic HR and LR. Pathway analysis showed that those proteins were most enriched in the acute phase response pathway. We prioritized candidate biomarkers for GC treatment based on the multivariate and pathway analysis. Next, we tested if those candidate biomarkers differed before and after GC treatment in nasal fluids from 40 patients with SAR using ELISA. Several proteins including ORM (P<0.0001), APOH (P<0.0001), FGA (P<0.01), CTSD (P<0.05) and SERPINB3 (P<0.05) differed significantly before and after GC treatment. Particularly, ORM (P<0.01), FGA (P<0.05) and APOH (P<0.01) that belonged to the acute phase response pathway decreased significantly in HR but not LR before and after GC treatment.
  
  
  CONCLUSIONS
  We identified several novel biomarkers for GC treatment response in SAR with combined proteomics, multivariate and pathway analysis. The analytical principles may be generally applicable to identify biomarkers in clinical studies of complex diseases.
authors: The Unit for Clinical Systems Biology, University of Gothenburg, Gothenburg, Sweden. hui.wang@gu.se
authors: Hui
authors: H
authors: Wang
authors: Johan
authors: J
authors: Gottfries
authors: Fredrik
authors: F
authors: Barrenäs
authors: Mikael
authors: M
authors: Benson
mesh_terms: D000210:Acute-Phase Reaction / Q000150:complications / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017817:Nasal Lavage Fluid; D040901:Proteomics / Q000379:methods*; D006255:Rhinitis, Allergic, Seasonal / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids