title: A genomic biomarker signature can predict skin sensitizers using a cell-based in vitro alternative to animal tests.
abstract: BACKGROUND
  Allergic contact dermatitis is an inflammatory skin disease that affects a significant proportion of the population. This disease is caused by an adverse immune response towards chemical haptens, and leads to a substantial economic burden for society. Current test of sensitizing chemicals rely on animal experimentation. New legislations on the registration and use of chemicals within pharmaceutical and cosmetic industries have stimulated significant research efforts to develop alternative, human cell-based assays for the prediction of sensitization. The aim is to replace animal experiments with in vitro tests displaying a higher predictive power.
  
  
  RESULTS
  We have developed a novel cell-based assay for the prediction of sensitizing chemicals. By analyzing the transcriptome of the human cell line MUTZ-3 after 24 h stimulation, using 20 different sensitizing chemicals, 20 non-sensitizing chemicals and vehicle controls, we have identified a biomarker signature of 200 genes with potent discriminatory ability. Using a Support Vector Machine for supervised classification, the prediction performance of the assay revealed an area under the ROC curve of 0.98. In addition, categorizing the chemicals according to the LLNA assay, this gene signature could also predict sensitizing potency. The identified markers are involved in biological pathways with immunological relevant functions, which can shed light on the process of human sensitization.
  
  
  CONCLUSIONS
  A gene signature predicting sensitization, using a human cell line in vitro, has been identified. This simple and robust cell-based assay has the potential to completely replace or drastically reduce the utilization of test systems based on experimental animals. Being based on human biology, the assay is proposed to be more accurate for predicting sensitization in humans, than the traditional animal-based tests.
authors.affiliation: Department of Immunotechnology, Lund University, BMC D13, 21184 Lund, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Johansson
authors.forename: Malin
authors.initials: M
authors.lastname: Lindstedt
authors.forename: Ann-Sofie
authors.initials: AS
authors.lastname: Albrekt
authors.forename: Carl A K
authors.initials: CA
authors.lastname: Borrebaeck
mesh_terms: D000826:Animal Testing Alternatives; D051940:B7-2 Antigen / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D045744:Cell Line, Tumor / Q000187:drug effects; D017449:Dermatitis, Allergic Contact / Q000209:etiology*; D006801:Humans; D023441:Local Lymph Node Assay; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D012372:ROC Curve; D012867:Skin / Q000187:drug effects; D060388:Support Vector Machine; D018675:Toxicity Tests / Q000379:methods*; D059467:Transcriptome
chemical_list: D051940:B7-2 Antigen; D015415:Biomarkers; C497964:CD86 protein, human