Interferon Responses in Eczema Herpeticum

Atopic Dermatitis Clinical Trial

— ADRN-01  

Official title:

Investigation of Reduced Interferon Responses in Peripheral Blood Mononuclear Cells of Participants With Atopic Dermatitis and a History of Eczema Herpeticum (ADRN-01)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01429311
• Other study ID #: DAIT ADRN-01
• Secondary ID: NIAID Funding Me
• Status: Completed
• Phase: N/A
• First received: July 19, 2011
• Last updated: April 26, 2017
• Start date: April 2011
• Est. completion date: January 2016

Study information

• Verified date: April 2017
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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 gamma (IFNγ) 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 IFNγ generation was significantly decreased after stimulation with HSV ex vivo. The purpose of this study is to determine if deficient IFNγ induction leads to susceptibility to HSV infection in ADEH+ patients.

Description:

The investigators hypothesize that defective IFNγ responses in peripheral blood mononuclear cells (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 IFNγ generation. This study will compare results from 40 ADEH+, 40 ADEH-, and 40 non-atopic participants.

Study procedures will typically be completed in one visit; however, participants may be asked to return for additional unscheduled visit(s) occurring as frequently as every 3 months for the duration of the study to provide an additional blood sample for further characterization of immune mechanisms leading to reduced IFNγ responses in ADEH+.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: January 2016
• Est. primary completion date: January 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

Participant Inclusion Criteria:

Participants who meet all of the following criteria are eligible for enrollment:

• have a history of AD with or without a history of Eczema Herpeticum (EH) as diagnosed using the Atopic Dermatitis Research Network (ADRN) Standard Diagnostic Criteria OR

--are non-atopic as diagnosed using the ADRN Standard Diagnostic Criteria

• 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

• 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:

• 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

• have an active systemic malignancy, excluding uncomplicated non-melanoma skin cancer

• 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)

• have a first degree relative already enrolled in the study

• 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:

• have active eczema herpeticum at the Enrollment Visit

• have taken systemic immunosuppressive drugs including cyclosporine or oral steroids within 30 days of the Enrollment Visit

• have a fever = 38.5 degrees Centigrade (ºC) (101.3 ºF) at the Enrollment Visit.

Related Conditions & MeSH terms

• Atopic Dermatitis
• Dermatitis
• Dermatitis, Atopic
• Eczema
• Eczema Herpeticum
• Eczema Vaccinatum
• Herpes Simplex
• Herpes Simplex Infections

Locations

Country	Name	City	State
United States	National Jewish Health	Denver	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Atopic Dermatitis Research Network

Country where clinical trial is conducted

United States, 

References & Publications (2)

Bin L, Edwards MG, Heiser R, Streib JE, Richers B, Hall CF, Leung DY. Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum. J Allergy Clin Immunol. 2014 Oct;134(4):848-55. doi: 10.1016/j.jaci.2014.07. — View Citation

Gao L, Bin L, Rafaels NM, Huang L, Potee J, Ruczinski I, Beaty TH, Paller AS, Schneider LC, Gallo R, Hanifin JM, Beck LA, Geha RS, Mathias RA, Barnes KC, Leung DY. Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of at — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Expression of IFN? and Interleukin-12 (IL-12), in response to stimulation with Herpes Simplex Virus 1 (HSV-1), Vaccinia Virus (VV), and Pattern Recognition Receptors (PRR) agonists	Protein and messenger ribonucleic acid (mRNA) levels of IFN?, and the IFN-? promoting cytokine, IL-12, produced by Cluster of Differentiation 14 (CD14+) monocytes in response to stimulation with HSV-1, VV, and various PRR agonists	Day 1
Secondary	Cell surface expression of Major Histocompatibility complex (MHC) class I and class II and co-stimulatory molecules on CD14+ cells in response to IFN? and Interferon-alpha (IFNa) stimulation		Day 1
Secondary	Production of IL-18 and IFNa protein and mRNA by CD14+ cells following stimulation with HSV-1, VV, or PRR agonists		Day 1
Secondary	Production of IFN? protein by Cluster of Differentiation 8 (CD8+) T cells in response to stimulation with recombinant human cytokines including but not limited to IL-12, IL-18, and IFNa		Day 1
Secondary	Protein expression of IFN? receptor and IFNa/ß receptor on CD14+ cells		Day 1
Secondary	Immunodominant HSV-1 peptide repertoires	Analysis of immunodominant HSV-1 peptide repertoires with related Human Leukocyte Antigen (HLA) in ADEH+, ADEH-, and non-atopic participants	Day 1
Secondary	High-throughput gene expression profiling to analyze ribonucleic acid (RNA) from HSV-1 stimulated and sham stimulated CD14+ monocytes	Global transcriptional response of CD14+ monocytes to stimulation with HSV-1 as evaluated by GeneChip Profiling	Day 1
Secondary	Production of protein and RNA of IFN family members and any related pro- or anti-inflammatory cytokines/chemokines in response to stimulation of PBMCs or purified monocytes	IFN family members include IFNa, Interferon beta (IFNß), and IFN?. Related pro- or anti-inflammatory cytokines/chemokines include, but are not limited to IL-29 and IL-10	Day 1
Secondary	Expression of MHC and co-stimulatory molecules on CD14+ cells in response to stimulation with HSV-1, VV, or PRR agonists		Day 1
Secondary	Viral titer of VV as determined by plaque assay following incubation of virus with PBMCs		Day 1
Secondary	Gene expression profiles and gene variant profiles of PBMCs stimulated with HSV-1 as assayed by RNA-seq		Day 1

External Links

•   Atopic Dermatitis Research Network (ADRN)
•   Division of Allergy, Immunology, and Transplantation (DAIT)
•   National Institute of Allergy and Infectious Diseases (NIAID)