Development of systems biology-oriented biomarkers by permuted stepwise regression for the monitoring of seasonal allergic rhinitis treatment effects

E.W. Baars, A.F.M. Nierop, H.F.J. Savelkoul

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Background: The immune system, a complex set of integrated responses, often cannot be explained, predicted, or monitored by examining its separate components as biomarkers. Combining different components may therefore be a suitable approach to develop relevant biomarkers reflecting immune system functioning in an appropriate way. Methods: Here we compute and test pattern variables that should reflect immune system functioning on the systems level. Computation was based on a dataset (from a randomized controlled trial comparing two routes of administration) of allergen-specifically induced expression levels of cytokines IL-1 beta, IL-5, IL-10, IL-12, IL-17, IFN-gamma and TNF-alpha) and symptom severity scores from 22 seasonal allergic rhinitis (SAR) patients measured before and after six weeks of treatment with medicinal products containing Citrus and Cydonia. By means of stepwise regression analyses we explored and tested pattern variables of the immunological data using permuted stepwise regression (PStR) to distinguish optimally between (immunological) baseline and post-baseline data for the whole treatment group (22 patients) and the two separate treatment groups (11 patients in each group). The validity of the stepwise selection method for the computed pattern variables was tested by means of random permutation tests and evaluated with the cross-validated correct rate of classification (CV correct). Results: For the total group a pattern variable was computed with three variables: IL-10 (day 7), TNF-alpha (day 1) and IL-10 (day 1) (CV correct: 091; p
Original languageEnglish
Pages (from-to)62-71
Number of pages10
JournalJournal of Immunological Methods
Volume378
Issue number1-2
DOIs
Publication statusPublished - 2012

Keywords

  • surrogate end-points
  • regulatory t-cells
  • gene polymorphisms
  • cytokine
  • immunotherapy
  • definitions
  • responses
  • patterns
  • children
  • healthy

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