Advanced

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

Johansson, Henrik LU ; Rydnert, Frida LU ; Kühnl, Jochen; Schepky, Andreas G; Borrebaeck, Carl LU and Lindstedt, Malin LU (2014) In Toxicological Sciences 139(2). p.362-370
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Toxicological Sciences
volume
139
issue
2
pages
362 - 370
publisher
Oxford University Press
external identifiers
  • pmid:24675087
  • wos:000337075900009
  • scopus:84899925111
ISSN
1096-0929
DOI
10.1093/toxsci/kfu046
language
English
LU publication?
yes
id
3e25c6be-7a95-4d2f-8559-dec8513ea18f (old id 4379585)
date added to LUP
2014-04-25 13:39:44
date last changed
2017-07-09 03:08:02
@article{3e25c6be-7a95-4d2f-8559-dec8513ea18f,
  abstract     = {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.},
  author       = {Johansson, Henrik and Rydnert, Frida and Kühnl, Jochen and Schepky, Andreas G and Borrebaeck, Carl and Lindstedt, Malin},
  issn         = {1096-0929},
  language     = {eng},
  number       = {2},
  pages        = {362--370},
  publisher    = {Oxford University Press},
  series       = {Toxicological Sciences},
  title        = {Genomic Allergen Rapid Detection In-House Validation—A Proof of Concept},
  url          = {http://dx.doi.org/10.1093/toxsci/kfu046},
  volume       = {139},
  year         = {2014},
}