Interferon Responses in Eczema Herpeticum

NCT ID: NCT01429311

Last Updated: 2017-04-28

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 84 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-04-30
• Study Completion Date: 2016-01-31

Brief 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.

Detailed 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+.

Conditions

Atopic Dermatitis; Eczema Herpeticum; Herpes Simplex Infections; Eczema Vaccinatum

Study Design

• Observational Model Type: OTHER
• Study Time Perspective: PROSPECTIVE

Study Groups

ADEH+

Subjects classified as Atopic Dermatitis (AD) and history of previous Eczema Herpeticum (EH) as defined by the ADRN Standard Diagnostic Criteria

No interventions assigned to this group

ADEH-

Subjects classified as AD without a history of EH as defined by the ADRN Standard Diagnostic Criteria

No interventions assigned to this group

Non-atopic Controls

Subjects classified as "Non-Atopic controls" as defined by the ADRN Standard Diagnostic Criteria

No interventions assigned to this group

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Atopic Dermatitis Research Network

OTHER

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Donald Leung, PhD, M.D

Role: PRINCIPAL_INVESTIGATOR

National Jewish Health

Locations

National Jewish Health

Denver, Colorado, United States

Countries

United States

References

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 DYM. Targeted deep sequencing identifies rare loss-of-function variants in IFNGR1 for risk of atopic dermatitis complicated by eczema herpeticum. J Allergy Clin Immunol. 2015 Dec;136(6):1591-1600. doi: 10.1016/j.jaci.2015.06.047. Epub 2015 Sep 3.

Reference Type: RESULT

PMID: 26343451 (View on PubMed)

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.2014.07.018. Epub 2014 Aug 23.

Reference Type: RESULT

PMID: 25159465 (View on PubMed)

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID)

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT)

Other Identifiers

NIAID Funding Mechanism

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

DAIT ADRN-01

Identifier Type: -

Identifier Source: org_study_id