An in vitro human skin test for assessing adverse immune reactions and sensitization potential

Abstract

A human in vitro skin explant test was developed by Alcyomics for the prediction of adverse immune reactions and assessment of relative potency. The skin explant test has a unique readout of histological damage, which ranges in severity from grade 0 and I (negative reaction) to grades II, III and IV damage (positive reaction) in human full-thickness skin. The test has been assessed for predicting responses to sensitizers and non-sensitizers, originally tested in the mouse local lymph node assay (LLNA). Results compared with the LLNA gave 95% specificity, 95% sensitivity and 95% concordance with a correlation coefficient of 0.9. Similar specificity and sensitivity were achieved for comparison of results to published human data with a correlation coefficient of 0.91. The test can also identify chemicals mis-classified in the mouse local lymph node assay (LLNA). Results of the skin test correlate with high or low T cell proliferation and IFNγ production, and these assays can be used as in vitro screening tests for compounds. Collectively, the human in vitro skin explant test can provide a robust, reliable and novel approach for characterization of sensitizing activity as a first step in the risk assessment process.