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.

Methodology/Principal Findings: We identified 953 nasal fluid proteins in symptomatic HR and LR with a LC MS/MS basedquantitative 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/Significance: 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.

Citation: Wang H, Gottfries J, Barrena¨s F, Benson M (2011) Identification of Novel Biomarkers in Seasonal Allergic Rhinitis by Combining Proteomic, Multivariate and Pathway Analysis. PLoS ONE 6(8): e23563. doi:10.1371/journal.pone.0023563

Editor: Harish Pant, National Institutes of Health, United States of America Received July 13, 2011; Accepted July 20, 2011; Published August 24, 2011

Copyright:  2011 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This research has been supported by the European Commission under the Seventh Framework Programme, grant agreement number 223367, MultiMod, the Swedish Medical Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.