Interferon Responses in Eczema Herpeticum (ADEH) (IFN)
Recruitment status was Recruiting
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Purpose
Atopic dermatitis (AD) is a chronic skin disorder characterized by recurrent viral skin infections. A small subset of patients with AD suffer from disseminated viral infections, e.g., eczema herpeticum (ADEH+), after herpes simplex infection (HSV) or eczema vaccinatum (EV) after smallpox vaccination. Interferon (IFN)-γ plays a critical role in the innate and acquired immune responses by activating macrophages, enhancing natural killer cell activation, and promoting T cell differentiation, as well as regulating B cell isotype switching to immunoglobulin (Ig) G2a. Recent studies have demonstrated that IFN-γ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFN-γ induction leads to susceptibility to HSV infection in ADEH+ patients.
| Condition |
|---|
|
Atopic Dermatitis Eczema Herpeticum Herpes Simplex Infections Eczema Vaccinatum |
| Study Type: | Observational |
| Study Design: | Time Perspective: Prospective |
| Official Title: | Investigation of Reduced Interferon Responses in Peripheral Blood Mononuclear Cells of Participants With Atopic Dermatitis and a History of Eczema Herpeticum |
- Expression of IFN and IL-12, in response to stimulation with HSV-1, VV, and PRR agonists. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Messenger ribonucleic acid (mRNA) levels of IFN, and the IFN promoting cytokine, IL-12, produced by CD14+ monocytes in response to stimulation with HSV-1, VV, and various PRR agonists.
- Cell surface expression of MHC class I/II and co-stimulatory molecules on CD14+ cells in response to IFN-gamma and IFN-alpha. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Expression of MHC class I/II and co-stimulatory molecules on CD14+ monocytes in response to IFN-gamma and IFN-alpha stimulation.
- IL-18 and IFN-α by CD14+ cells following stimulation with HSV-1, VV, and PRR agonists. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Production of IL-18 and IFN-α and mRNA by CD14+ cells following stimulation with HSV-1, VV, or PRR agonists.
- IFN-γ production by CD8+ T cells, in response to stimulation with cytokines IL-12, IL-18, and IFN-α. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Production of IFN-γ by CD8+ T cells in response to stimulation with recombinant human cytokines including but not limited to IL-12, IL-18, and IFN-α.
- Expression of IFN-γ receptor and IFN- α/β receptor on CD14+ cells. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Expression of IFN-γ receptor and IFN- α/β receptor on CD14+ cells.
- Immunodominant HSV-1 peptide repertoires. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Analysis of immunodominant HSV-1 peptide repertoires with related HLA in ADEH+, ADEH-, and non-atopic participants.
- High-throughput gene expression profiling to analyze ribonucleic acid (RNA) from HSV-1 stimulated and sham stimulated CD14+ monocytes. [ Time Frame: Day 1 ] [ Designated as safety issue: No ]Global transcriptional response of CD14+ monocytes to stimulation with HSV-1 as evaluated by GeneChip Profiling.
Biospecimen Retention: Samples With DNA
Blood samples, RNA, serum, and cells will be retained.
| Estimated Enrollment: | 60 |
| Study Start Date: | April 2011 |
| Groups/Cohorts |
|---|
| 20 ADEH+ |
| 20 ADEH- |
| 20 Non-atopic controls |
Detailed Description:
Atopic dermatitis (AD) is a chronic skin disorder characterized by recurrent viral skin infections. A small subset of patients with AD suffer from disseminated viral infections, e.g., eczema herpeticum (ADEH+), after herpes simplex infection (HSV) or eczema vaccinatum (EV) after smallpox vaccination. Interferon (IFN)-γ plays a critical role in the innate and acquired immune responses by activating macrophages, enhancing natural killer cell activation, and promoting T cell differentiation, as well as regulating B cell isotype switching to immunoglobulin (Ig)G2a. Recent studies have demonstrated that IFN-γ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFN-γ induction leads to susceptibility to HSV infection in ADEH+ patients.
We hypothesize that defective IFN-γ responses in PBMCs from ADEH+ patients results from aberrant pattern recognition receptors (PRR) signaling in antigen-presenting cells (APCs) resulting in low level production of IL-12, an essential cytokine for IFN-γ generation. We will compare results from 20 ADEH+, 20 ADEH-, and 20 non-atopic participants.
Study procedures will typically be completed in one visit; however, participants may complete a second visit if they do not meet eligibility criteria, or are asked to provide an additional blood sample for further characterization of immune mechanisms leading to reduced IFN-γ responses in ADEH+.
Eligibility| Ages Eligible for Study: | 6 Years to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
| Sampling Method: | Non-Probability Sample |
20 ADEH+, 20 ADEH-, and 20 non-atopic controls 6 to 65 years of age. Due to the intended age range, ADEH- and non-atopic control participants will be gender- and age-matched to ADEH+ participants.
Participant Inclusion Criteria:
Participants who meet all of the following criteria are eligible for enrollment. Participants may be reassessed if not initially eligible.
- Who are males and females 6 to 65 years of age, inclusive, at the Enrollment Visit.
- Who have a history of AD with or without a history of EH as diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria OR who are non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria.
- Who are willing to sign the informed consent form or whose parent or legal guardian is willing to sign the informed consent form (age appropriate) prior to initiation of any study procedure.
- Who are willing to sign the assent form, if age appropriate.
Participant Exclusion Criteria:
Participants who meet any of the following criteria are not eligible for enrollment.
- Who have a history of any systemic illness (e.g., immunodeficiency disorders such as human immunodeficiency virus [HIV] or lupus erythematosus) other than the condition being studied.
- Who have an active systemic malignancy, excluding uncomplicated non-melanoma skin cancer.
- Who have any skin disease other than AD that might compromise the stratum corneum barrier (e.g., bullous disease, psoriasis, cutaneous T cell lymphoma [also called Mycosis Fungoides or Sezary syndrome], dermatitis herpetiformis, Hailey-Hailey, or Darier's disease).
- Who have a first degree relative already enrolled in the study.
- Who are determined not to be eligible in the opinion of the Investigator.
Participants who meet any of the following criteria are not eligible for enrollment but may be reassessed.
- Who have active eczema herpeticum at the Enrollment Visit.
- Who have taken systemic immunosuppressive drugs including cyclosporine or oral steroids within 30 days of the Enrollment Visit.
- Who have a fever ≥ 38.5 ºC (101.3 ºF) at the Enrollment Visit.
Contacts and Locations| United States, Colorado | |
| National Jewish Health | Recruiting |
| Denver, Colorado, United States, 80206 | |
| Contact: Judy Lairsmith 303-270-2413 lairsmithj@NJHealth.org | |
| Contact: Gayle Spears, NP (303) 398-1852 spearsg@njhealth.org | |
| Principal Investigator: | Donald Leung, PhD, M.D | National Jewish Health |
More Information
No publications provided
| Responsible Party: | Donald Leung MD, PhD [Principal Investigator], National Jewish Health |
| ClinicalTrials.gov Identifier: | NCT01429311 History of Changes |
| Other Study ID Numbers: | ADRN-01, NIAID Funding Mechanism |
| Study First Received: | July 19, 2011 |
| Last Updated: | September 2, 2011 |
| Health Authority: | United States: Institutional Review Board United States: Federal Government |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
Atopic Dermatitis, Eczema herpecticum, Interferon |
Additional relevant MeSH terms:
|
Herpes Simplex Dermatitis Dermatitis, Atopic Eczema Kaposi Varicelliform Eruption Skin Diseases Skin Diseases, Genetic Genetic Diseases, Inborn Skin Diseases, Eczematous Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |
Herpesviridae Infections DNA Virus Infections Virus Diseases Skin Diseases, Viral Skin Diseases, Infectious Interferons Antineoplastic Agents Therapeutic Uses Pharmacologic Actions Antiviral Agents Anti-Infective Agents |
ClinicalTrials.gov processed this record on May 19, 2013