Etiology of Eczema Herpeticum (EH)
Słowa kluczowe
Abstrakcyjny
Opis
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.
Daktyle
| Ostatnia weryfikacja: | 06/30/2020 |
| Pierwsze przesłane: | 01/24/2017 |
| Szacowana liczba przesłanych rejestracji: | 01/29/2017 |
| Wysłany pierwszy: | 01/31/2017 |
| Ostatnia aktualizacja przesłana: | 07/05/2020 |
| Ostatnia opublikowana aktualizacja: | 07/07/2020 |
| Rzeczywista data rozpoczęcia badania: | 02/21/2017 |
| Szacowana data zakończenia podstawowej działalności: | 08/30/2020 |
| Szacowana data zakończenia badania: | 08/30/2020 |
Stan lub choroba
Faza
Grupy ramion
| Ramię | Interwencja / leczenie |
|---|---|
| Discovery Cohort A minimum of 50 recurrent Atopic Dermatitis with a history of Eczema Herpeticum(ADEH+), 500 Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-), and 237 Non-Atopic (NA) European American participants from the Atopic Dermatitis Research Network (ADRN) DNA Repository.
The study will learn from this cohort:
All Single Nucleotide Variants (SNVs) in ADEH+
ADEH+ specific deleterious SNVs
The study will determine the function of:
4. ADEH+ risk variants | |
| Independent populations of participants Two independent populations of participants:
Children, aged 3-17 years and
Adults 18-64 years of age.
A minimum of 12 recurrent Atopic Dermatitis with a history of Eczema Herpeticum (ADEH+) with ≥3 Eczema Herpeticum (EH) episodes, 12 Atopic Dermatitis without a history of Eczema Herpeticum (ADEH-) and 12 Non-Atopic (NA) participants will be enrolled in each of the two populations. |
Kryteria kwalifikacji
| Wiek kwalifikujący się do nauki | 3 Years Do 3 Years |
| Płeć kwalifikująca się do nauki | All |
| Metoda próbkowania | Non-Probability Sample |
| Przyjmuje zdrowych wolontariuszy | tak |
| Kryteria | Inclusion Criteria: 1. Must be a participant already enrolled in the ADRN Registry and provided DNA (ClinicalTrials.gov ID: NCT01494142); 2. Participant and/or parent guardian must be able to understand and provide informed consent; 3. A history of Atopic Dermatitis (AD) with a history of eczema herpeticum (ADEH+), as diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria, with ≥3 episodes of Eczema Herpeticum (EH) OR A history of AD without a history of eczema herpeticum (ADEH-), as diagnosed using the ADRN Standard Diagnostic Criteria, and no immediate family members (mother, father, full siblings, half-siblings, offspring, aunts, uncles, cousins, or grandparents) with a history of EH OR Non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria. 4. Anti-Herpes Simplex Virus (HSV)-1 or Anti-HSV-2 Immunoglobulin G (IgG) seropositive. Exclusion Criteria: 1. Inability or unwillingness of a participant and/or parent guardian to give written informed consent or comply with study protocol; 2. Pregnant or lactating women; 3. Known or suspected immunosuppression; 4. Severe concomitant illness(es); 5. History of keloid formation (adults only); 6. History of lidocaine or Novocain allergy (adults only); 7. History of serious life-threatening reaction to latex, tape, or adhesives; 8. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. 9. Use of biologics within 5 half-lives (if known) or 16 weeks of the Screening Visit; 10. Use of an investigational drug within 5 half-lives (if known) or 8 weeks of the Screening Visit. |
Wynik
Podstawowe miary wyników
1. 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 [3 years]
2. 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 [3 years]
Miary wyników wtórnych
1. Gene expression profiles in the dermis [3 years]
2. Gene expression profiles in the epidermis [3 years]
3. Gene expression profiles in in keratinocytes [3 years]
4. Gene expression profiles in fibroblasts [3 years]
5. Gene expression profiles in peripheral blood Plasmacytoid Dendritic Cells(pDCs) [3 years]
6. Gene expression profiles in skin tape strip samples [3 years]
7. Herpes Simplex Virus (HSV) replication in primary keratinocytes [3 years]
8. Herpes Simplex Virus (HSV) replication in fibroblasts [3 years]
9. Herpes Simplex Virus (HSV) replication in Plasmacytoid Dendritic Cells (pDCs) [3 years]
10. Herpes Simplex Virus (HSV) replication in genetically modified cell lines [3 years]
11. Anti-viral responses in primary keratinocytes [3 years]
12. Anti-viral responses in fibroblasts [3 years]
13. Anti-viral responses in Plasmacytoid Dendritic Cells (pDCs) [3 years]
14. Anti-viral responses in genetically modified cell lines [3 years]
15. Immune responses in primary keratinocytes [3 years]
16. Immune responses in fibroblasts [3 years]
17. Immune responses in Plasmacytoid Dendritic Cells (pDCs) [3 years]
18. Immune responses in genetically modified cell lines [3 years]
19. Differentiation markers in primary keratinocytes [3 years]
20. Differentiation markers in genetically modified keratinocyte cell lines [3 years]
21. Expression of reporter gene constructs testing non-coding variants [3 years]
22. Exploratory: Viral carriage [3 years]
23. Exploratory: Protein expression of epidermal differentiation complex [3 years]
24. Exploratory: Protein expression of inflammatory genes [3 years]
25. Exploratory: Lipid profiles [3 years]
26. Exploratory: Whole-genome DNA methylation profiles from epidermis [3 years]
27. Exploratory: Whole-genome DNA methylation profiles from dermis [3 Years]
