Atopic dermatitis, also called eczema, is a disease with dry, scaly, itchy skin. Those with atopic dermatitis may have complications from skin infections such as eczema herpeticum after herpes simplex virus (HSV) infection. Symptoms of eczema herpeticum include fever and clusters of itchy blisters which crust over and form sores. Although exposure to HSV is widespread, most people clear the virus and only a subset of individuals with atopic dermatitis develop eczema herpeticum. The purpose of this study is to determine why some individuals with atopic dermatitis are at higher risk for recurrent skin infections with HSV. The study team will compare how people with atopic dermatitis with a history of recurrent eczema herpeticum, people with atopic dermatitis without a history of eczema herpeticum, and people without atopic dermatitis respond to HSV.
This study uses whole genome sequencing (WGS) technology to identify genetic variants that confer risk of recurrent atopic dermatitis with a history of eczema herpeticum (ADEH+), with ≥3 eczema herpeticum (EH) episodes. A small subgroup of individuals with atopic dermatitis (AD) suffer from life-threatening disseminated herpes simplex virus (HSV) skin infections, termed eczema herpeticum (ADEH+). The manifestation of ADEH+ however is not simply a consequence of herpes simplex virus type 1 (HSV-1) infections, since the majority of the US population is latently infected with HSV-1 from an early age. Most importantly, there is a bimodality in the recurrence of eczema herpeticum (EH) episodes; most individuals have only a single episode but a subgroup of ADEH+ individuals has 3 or more episodes. This study aims to conduct an extreme trait investigation of ADEH+ with recurrent EH, ≥3 episodes, compared to AD without a history of eczema herpeticum (ADEH-), using whole genome sequencing.
Study Type
OBSERVATIONAL
Enrollment
69
National Jewish Health: Division of Pediatric Allergy and Clinical Immunology
Denver, Colorado, United States
The Difference in Frequency of Rare Deleterious Coding Genetic Variants between Subjects with Recurrent Atopic Dermatitis (AD) and a History of Eczema Herpeticum (ADEH+) Compared to Controls - Using Whole Genome Sequencing
Whole genome sequencing methodology will be used to identify differences in frequency of rare deleterious coding genetic variants between recurrent Atopic Dermatitis (AD) subjects with a history of Eczema Herpeticum (ADEH+) and ≥3 Eczema Herpeticum (EH) episodes, versus controls. Controls will include (1) AD subjects without a history of EH (ADEH-); (2) non-atopic (NA) subjects without AD; and (3) general population controls from the Thousand Genomes Project.
Time frame: 3 years
The Difference in Frequency of Rare Deleterious Non-Coding Genetic Variants between Subjects with Recurrent Atopic Dermatitis (AD) and a History of Eczema Herpeticum (ADEH+) Compared to Controls - Using Whole Genome Sequencing
Whole genome sequencing methodology will be used to identify differences in frequency of rare deleterious non-coding genetic variants between subjects with recurrent Atopic Dermatitis (AD) subjects and a history of Eczema Herpeticum (ADEH+) with ≥3 Eczema Herpeticum (EH) episodes, versus controls. Controls will include (1) AD subjects without a history of EH (ADEH-); (2) non-atopic (NA) subjects without AD; and (3) general population controls from the Thousand Genomes Project.
Time frame: 3 years
Gene expression profiles in the dermis
Time frame: 3 years
Gene expression profiles in the epidermis
Time frame: 3 years
Gene expression profiles in in keratinocytes
Time frame: 3 years
Gene expression profiles in fibroblasts
Time frame: 3 years
Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs)
Time frame: 3 years
Gene expression profiles in skin tape strip samples
Time frame: 3 years
Herpes Simplex Virus (HSV) replication in primary keratinocytes
HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
Time frame: 3 years
Herpes Simplex Virus (HSV) replication in fibroblasts
HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
Time frame: 3 years
Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs)
HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
Time frame: 3 years
Herpes Simplex Virus (HSV) replication in genetically modified cell lines
HSV replication will be assessed by HSV copy number by Polymerase Chain Reaction (PCR) or RNA sequencing.
Time frame: 3 years
Anti-viral responses in primary keratinocytes
Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\])
Time frame: 3 years
Anti-viral responses in fibroblasts
Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\])
Time frame: 3 years
Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs)
Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\]).
Time frame: 3 years
Anti-viral responses in genetically modified cell lines
Anti-viral responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\]).
Time frame: 3 years
Immune responses in primary keratinocytes
Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\]).
Time frame: 3 years
Immune responses in fibroblasts
Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\]).
Time frame: 3 years
Immune responses in Plasmacytoid Dendritic Cells (pDCs)
Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\]).
Time frame: 3 years
Immune responses in genetically modified cell lines
Immune responses will be measured by cytokine production and antimicrobial responses (e.g. interferons \[IFNs\], tumor necrosis factor alpha \[TNFalpha\], LL-37, human beta-defensins \[HBDs\])
Time frame: 3 years
Differentiation markers in primary keratinocytes
Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).
Time frame: 3 years
Differentiation markers in genetically modified keratinocyte cell lines
Differentiation markers (e.g. filaggrin (FLG), involucrin, loricrin, and Human Beta-Defensins (HBDs)).
Time frame: 3 years
Expression of reporter gene constructs testing non-coding variants
Time frame: 3 years
Exploratory: Viral carriage
Viral carriage will be assessed by presence of viral sequencing reads.
Time frame: 3 years
Exploratory: Protein expression of epidermal differentiation complex
Protein expression of epidermal differentiation complex will be measured by Mass Spectroscopy of skin tape strips.
Time frame: 3 years
Exploratory: Protein expression of inflammatory genes
Protein expression of inflammatory genes will be measured by Mass Spectroscopy of skin tape strips.
Time frame: 3 years
Exploratory: Lipid profiles
Lipid profiles will be measured by mass spectroscopy of skin tape strips.
Time frame: 3 years
Exploratory: Whole-genome DNA methylation profiles from epidermis
Time frame: 3 years
Exploratory: Whole-genome DNA methylation profiles from dermis
Time frame: 3 Years
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