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Genomic Allergen Rapid Detection In-House Validation—A Proof of Concept

Author:
  • Henrik Johansson
  • Frida Rydnert
  • Jochen Kühnl
  • Andreas G Schepky
  • Carl Borrebaeck
  • Malin Lindstedt
Publishing year: 2014
Language: English
Pages: 362-370
Publication/Series: Toxicological Sciences
Volume: 139
Issue: 2
Document type: Journal article
Publisher: Oxford University Press

Abstract english

Chemical sensitization is an adverse immunologic response to chemical substances, inducing hypersensitivity in exposed individuals. Identifying chemical sensitizers is of great importance for chemical, pharmaceutical and cosmetic industry, in order to prevent the use of sensitizers in consumer products. Historically, chemical sensitizers have been assessed mainly by in vivo methods, however, recently enforced European legislations urge and promote the development of animal-free test methods able to predict chemical sensitizers. Recently, we presented a predictive biomarker signature in the myeloid cell line MUTZ-3, for assessment of skin sensitizers. The identified genomic biomarkers were found to be involved in immunologically relevant pathways, induced by recognition of foreign substances and regulating dendritic cell maturation and cytoprotective mechanisms. We have developed the usage of this biomarker signature into a novel in vitro assay for assessment of chemical sensitizers, called Genomic Allergen Rapid Detection, GARD. The assay is based on chemical stimulation of MUTZ-3 cultures, using the compounds to be assayed as stimulatory agents. The readout of the assay is a transcriptional quantification of the genomic predictors, collectively termed the GARD Prediction Signature, using a complete genome expression array. Compounds are predicted as either sensitizers or non-sensitizers by a Support Vector Machine model. In this report, we provide a proof of concept for the functionality of the GARD assay by describing the classification of 26 blinded and 11 non-blinded chemicals as sensitizers or non-sensitizers. Based on these classifications, the accuracy, sensitivity and specificity of the assay was estimated to 89%, 89% and 88%, respectively.

Keywords

  • Immunology in the medical area

Other

Published
  • ISSN: 1096-0929
Carl Borrebaeck
E-mail: carl [dot] borrebaeck [at] immun [dot] lth [dot] se

Professor

Department of Immunotechnology

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