• English
    • svenska
  • svenska 
    • English
    • svenska
  • Logga in
Redigera dokument 
  •   Startsida
  • Sahlgrenska Academy / Sahlgrenska akademin
  • Institute of Clinical Sciences / Institutionen för kliniska vetenskaper
  • Doctoral Theses / Doktorsavhandlingar Institutionen för kliniska vetenskaper
  • Redigera dokument
  •   Startsida
  • Sahlgrenska Academy / Sahlgrenska akademin
  • Institute of Clinical Sciences / Institutionen för kliniska vetenskaper
  • Doctoral Theses / Doktorsavhandlingar Institutionen för kliniska vetenskaper
  • Redigera dokument
JavaScript is disabled for your browser. Some features of this site may not work without it.

Systems Biology Based Approaches to Identify Biomarkers in Seasonal Allergic Rhinitis

Sammanfattning
Glucocorticoids (GC) are the most effective anti-inflammatory treatment for seasonal allergic rhinitis (SAR). However, a few patients with SAR show poor response to GC treatment. Hence, there is a clinical need to find biomarkers to predict and monitor treatment response. Given that GC may affect the expression of a large amount of genes and proteins in different cells and tissues from SAR, it is a formidable challenge to understand these complex changes and to identify candidate biomarkers by studying individual genes. The aim of the study was to develop systems biology based approaches to identify biomarkers for GC treatment response in SAR. To achieve this goal, clinical investigations, experimental studies and bioinformatics analyses were combined. We profiled gene- and/or protein expression in nasal mucosa, nasal fluids and in vitro allergen-challenged CD4+ T cells from patients with SAR by gene expression microarray- and quantitative proteomics analysis. Ingenuity pathway analysis (IPA) and/or multivariate analysis were employed to prioritize candidate biomarkers and genes of importance to allergy. We further validated candidate biomarkers by ELISA. We showed that several pathways, such as the acute phase response pathway, were enriched with genes-coding proteins that may be candidate biomarkers. We identified several novel biomarkers for GC treatment response in SAR including orosomucoid (ORM), apoliprotein H (ApoH) and fibrinogen alpha chain (FGA). With integrated multivariate and pathway analyses we also demonstrated that the expression of allergen-induced genes in CD4+ T cells from patients with SAR was reversed by GC treatment. We indentified that increased IFN-γ activity in allergen-challenged CD4+ T cells was decreased by GC treatment. In conclusion, we developed systems biology based approaches for the identification of novel biomarkers in SAR. These approaches may be generally applicable to identify biomarkers in clinical studies of complex diseases.
Delarbeten
I. Wang H., Barrenäs F., Bruhn S., Mobini R. & Benson M. Increased IFN-γ activity in seasonal allergic rhinitis is decreased by corticosteroid treatment. J Allergy Clin Immunol (2009); 124(6):1360-2. ::PMID::19910031
 
II. Wang H., Chavali S., Mobini R., Muraro A., Barbon F., Boldrin D., Åberg N. & Benson M. A pathway-based approach to find novel markers of local glucocorticoid treatment in intermittent allergic rhinitis. Allergy (2011); 66(1):132-40. ::PMID::20659080
 
III. Wang H., Gottfries J., Barrenäs F. & Benson M. Identification of Novel Biomarkers in Seasonal Allergic Rhinitis by Combining Proteomic, Multivariate and Pathway Analysis. PLoS One (2011); 6(8):e23563 ::PMID::21887273
 
IV. Zhao Y., Wang H., Gustafsson M., Muraro A., Bruhn S. & Benson M. Combined Multivariate and Pathway Analyses Show That Allergen-Induced Gene Expression Changes in CD4+ T Cells Are Reversed by Glucocorticoids. PLoS One (2012); 7(6):e39016. ::PMID::22701743
 
Examinationsnivå
Doctor of Philosophy (Medicine)
Universitet
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Clincial Sciences. Department of Pediatrics
Disputation
Fredagen den 21 September 2012, kl. 13.00, Föreläsningssal 1, Drottning Silvias barn- och ungdomssjukhus, SU/Östra, Göteborg
Datum för disputation
2012-09-21
E-post
hui.wang@gu.se
URL:
http://hdl.handle.net/2077/30125
Samlingar
  • Doctoral Theses / Doktorsavhandlingar Institutionen för kliniska vetenskaper
  • Doctoral Theses from Sahlgrenska Academy
  • Doctoral Theses from University of Gothenburg / Doktorsavhandlingar från Göteborgs universitet
Fil(er)
Thesis frame (1.093Mb)
Abstract (99.20Kb)
Datum
2012-09-12
Författare
Wang, Hui
Nyckelord
Glucocorticoids
Seasonal allergic rhinitis
Biomarkers
Gene expression microarray analysis
Proteomics
Multivariate analysis
Pathway analysis
Publikationstyp
Doctoral thesis
ISBN
978-91-628-8508-3
Språk
eng
Metadata
Visa fullständig post

DSpace software copyright © 2002-2016  DuraSpace
gup@ub.gu.se | Teknisk hjälp
Theme by 
Atmire NV
 

 

Visa

VisaSamlingarI datumordningFörfattareTitlarNyckelordDenna samlingI datumordningFörfattareTitlarNyckelord

Mitt konto

Logga inRegistrera dig

DSpace software copyright © 2002-2016  DuraSpace
gup@ub.gu.se | Teknisk hjälp
Theme by 
Atmire NV