title: The gene expression and immunohistochemical time-course of diphenylcyclopropenone-induced contact allergy in healthy humans following repeated epicutaneous challenges.
abstract: The gene expression time-course of repeated challenge of contact allergy (CA) remains largely unknown. Therefore, using diphenylcyclopropenone (DPCP) as model allergen in healthy humans we set out to examine: (i) the monotonous and complex gene expression time-course trajectories following repeated DPCP challenges to find the predominant gene expression pattern, (ii) the time-course of cell infiltration following repeated DPCP challenges and (iii) the transcriptome of a repeated CA exposure model. We obtained punch biopsies from control and DPCP-exposed skin from ten DPCP sensitized individuals at 5-6 monthly elicitation challenges. Biopsies were used for microarray gene expression profiling, histopathology and immunohistochemical staining. Validation of microarray data by qRT-PCR was performed on 15 selected genes. Early gene expression time points were also validated in an independent data set. An increasing and decreasing trend in gene expression followed by a plateau was predominantly observed during repeated DPCP challenges. Immune responses reached a plateau after two challenges histopathologically, immunohistochemically and in the time-course gene expression analysis. Transcriptional responses over time revealed a Th1/Th17 polarization as three upstream regulators (IFN-γ, IL-1 and IL-17) activated most of the top upregulated genes. Of the latter genes, 9 of 10 were the same throughout the time course. Excellent correlations between array and PCR data were observed. The transcriptional responses to DPCP over time followed a monotonous pattern. This response pattern confirms and supports the newly reported clinical time-course observations in de novo-sensitized individuals showing a plateau response, and thus, there is concordance between clinical response, histopathology, immunohistochemistry and microarray gene expression in volunteers de novo-sensitized to DPCP.
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.|Dermatological Investigations Scandinavia, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Kristian F
authors.identifier: 0000-0003-3689-7350
authors.initials: KF
authors.lastname: Mose
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Mark
authors.initials: M
authors.lastname: Burton
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Mads
authors.initials: M
authors.lastname: Thomassen
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.|Dermatological Investigations Scandinavia, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Flemming
authors.initials: F
authors.lastname: Andersen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Torben A
authors.initials: TA
authors.lastname: Kruse
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.|Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, Odense C, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Dermato-Allergology, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Skov
authors.affiliation: Departments of Clinical Pharmacology and Molecular Biomedicine, LEO Pharma A/S, Ballerup, Denmark.
authors.forename: Mads A
authors.initials: MA
authors.lastname: Røpke
authors.affiliation: Departments of Clinical Pharmacology and Molecular Biomedicine, LEO Pharma A/S, Ballerup, Denmark.|Department of Immunology and Microbiology, University of Copenhagen, Copenhagen N, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Litman
authors.affiliation: Department of Clinical Pathology, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Clemmensen
authors.affiliation: Department of Clinical Pathology, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.
authors.forename: Bjarne W
authors.initials: BW
authors.lastname: Kristensen
authors.affiliation: Division of Infection, Inflammation & Immunity, Sir Henry Wellcome Laboratories, Southampton University Hospitals NHS Trust, Southampton, UK.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Friedmann
authors.affiliation: Department of Dermatology and Allergy Centre, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.|Dermatological Investigations Scandinavia, Odense University Hospital, University of Southern Denmark, Odense C, Denmark.|Centre for Innovative Medical Technology, Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark.
authors.forename: Klaus E
authors.initials: KE
authors.lastname: Andersen
mesh_terms: D000328:Adult; D001706:Biopsy; D003521:Cyclopropanes; D017449:Dermatitis, Allergic Contact / Q000209:etiology / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D064368:Healthy Volunteers; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007375:Interleukin-1 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D013997:Time Factors; D059467:Transcriptome; D055815:Young Adult
chemical_list: D003521:Cyclopropanes; D007375:Interleukin-1; D020381:Interleukin-17; D007371:Interferon-gamma; C029402:diphenylcyclopropenone
keywords: de novo sensitization; microarray; rechallenge; time-course analysis; transcriptional profiling