title: An in vivo tiered approach to test immunosensitization by low molecular weight compounds.
abstract: New chemical entities are tested in general toxicity assays during development before entering clinical trials. However, immunosensitization of these entities is not tested on a standard basis. There are no in vitro or in vivo standardized methods available for testing immunosensitization or immunostimulation. In this chapter, we describe a tiered strategy oral exposure model for assessing immunosensitization or immunostimulation capacity of low molecular weight compounds. The strategy starts from a set of data that may provide information on bioactivation, conjugation (hapten-protein conjugate formation), cytotoxicity and signs of inflammation in any of the animals in a 28 day-toxicity study. In case of concern, a reporter antigen-popliteal lymph node assay (RA-PLNA) and, subsequently, an oral exposure experiment with the reporter antigen can be performed. Based on the presence of RA-specific immune responses an indication for immunosensitization can be found.
authors.forename: Irene S
authors.initials: IS
authors.lastname: Ludwig
authors.forename: Lydia M
authors.initials: LM
authors.lastname: Kwast
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Fiechter
authors.forename: Raymond H H
authors.initials: RH
authors.lastname: Pieters
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D018929:Cell Culture Techniques; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008970:Molecular Weight; D011897:Random Allocation; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens