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Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent viral skin infections. Recent studies have demonstrated that the skin of people with AD my have decreased antimicrobial peptide (AMP) expression. The purpose of this study is to compare smallpox virus replication and the number of AMPs and other antiviral molecules in people with AD, as compared to those seen in people with psoriasis or asthma, or healthy individuals.
AD is a chronic inflammatory skin disease characterized by frequent viral skin infections. Recent studies have found that components in the skin of people with AD may block AMP expression. AMPs are responsible for preventing infection from viruses. The purpose of this study is to examine smallpox virus replication and AMP expression in the skin of patients with AD as well as identify other antiviral molecules involved in immune response. These findings will be compared with those of people with psoriasis or asthma, or healthy individuals. This study will consist of one study visit at which skin and blood samples will be taken.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Atopic Dermatitis (AD) | Pediatric and adult subjects who fulfill the criteria for AD, a chronic inflammatory skin disease. | ||
| Inactive Atopic Dermatitis (AD) | Adult subjects with a prior history of active AD that has been quiescent for at least 1 year. | ||
| Psoriatics | Adult subjects who fulfill the criteria for plaque psoriasis, a chronic inflammatory skin disease. | ||
| Asthmatics (without a history of AD) | Adult subjects who fulfill the criteria for asthma (reactive airway disease) and have a negative history of skin disease. | ||
| Eczema Herpeticum (EH | Pediatric and adult AD subjects with a history of EH. | ||
| Healthy Volunteers | Healthy individuals with no history of skin or respiratory disease. |
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| Measure | Description | Time Frame |
|---|---|---|
| Expression of vaccinia virus mRNA in non-lesional skin following inoculation with untreated vaccinia virus will be evaluated using real-time RT-PCR (Reverse transcription polymerase chain reaction). | 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Expression of cytokines, AMPs, other antiviral molecules, or epidermal differentiation proteins in non-lesional skin prior to and after inoculation with vaccinia virus will be evaluated using real-time RT-PCR. | 5 years | |
| Keratinocytes will be stimulated with vaccinia virus in the presence and absence of Th1 or Th2 cytokines. Non-lesional AD skin will be stimulated with vaccinia virus in the presence of antibodies that neutralize Th2 cytokines. |
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Inclusion Criteria for Participants With AD:
Inclusion Criteria for Participants With Asthma or Psoriasis, and for non-atopic controls:
Exclusion Criteria:
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People of good general health
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| Name | Affiliation | Role |
|---|---|---|
| Donald Leung, MD, PhD | National Jewish Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Jewish Health | Denver | Colorado | 80207 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14734759 | Background | Howell MD, Jones JF, Kisich KO, Streib JE, Gallo RL, Leung DY. Selective killing of vaccinia virus by LL-37: implications for eczema vaccinatum. J Immunol. 2004 Feb 1;172(3):1763-7. doi: 10.4049/jimmunol.172.3.1763. | |
| 12960356 | Background | Nomura I, Goleva E, Howell MD, Hamid QA, Ong PY, Hall CF, Darst MA, Gao B, Boguniewicz M, Travers JB, Leung DY. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 2003 Sep 15;171(6):3262-9. doi: 10.4049/jimmunol.171.6.3262. |
| Label | URL |
|---|---|
| National Institute of Allergy and Infectious Diseases (NIAID) | View source |
| ID | Type | URL | Comment |
|---|---|---|---|
| SDY10 | Individual Participant Data Set | View IPD |
Participant level data and additional relevant materials are available to the public in the Immunology Database and Analysis Portal (ImmPort). ImmPort is a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
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| ID | Term |
|---|---|
| D003876 | Dermatitis, Atopic |
| ID | Term |
|---|---|
| D012873 | Skin Diseases, Genetic |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D003872 | Dermatitis |
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Blood and skin samples will be retained
| 5 years |
| Vaccinia virus replication will be evaluated using a standard viral plaque assay in BS-C-1 cells and by analyzing vaccinia virus mRNA expression using real-time RT-PCR in keratinocytes and BS-C-1 cells. | 5 years |
| Expression of over 20,000 genes will be evaluated by GeneChip microarrays in non-lesional skin, and PBMCs stimulated with vaccinia virus. Real-time RT-PCR of skin and PBMC will be used to confirm gene alterations found in GeneChip microarrays. | 5 years |
| Ability of structural analogues of CSAs (Cyclosporine) to kill purified vaccinia virus as well as keratinocytes infected with vaccinia virus in vitro. | 5 years |
| 16630942 | Background | Howell MD, Wollenberg A, Gallo RL, Flaig M, Streib JE, Wong C, Pavicic T, Boguniewicz M, Leung DY. Cathelicidin deficiency predisposes to eczema herpeticum. J Allergy Clin Immunol. 2006 Apr;117(4):836-41. doi: 10.1016/j.jaci.2005.12.1345. Epub 2006 Feb 14. |
| 14991059 | Background | Leung DY, Boguniewicz M, Howell MD, Nomura I, Hamid QA. New insights into atopic dermatitis. J Clin Invest. 2004 Mar;113(5):651-7. doi: 10.1172/JCI21060. |
| 16546102 | Result | Howell MD, Gallo RL, Boguniewicz M, Jones JF, Wong C, Streib JE, Leung DY. Cytokine milieu of atopic dermatitis skin subverts the innate immune response to vaccinia virus. Immunity. 2006 Mar;24(3):341-8. doi: 10.1016/j.immuni.2006.02.006. |
| 21762972 | Result | Howell MD, Gao P, Kim BE, Lesley LJ, Streib JE, Taylor PA, Zaccaro DJ, Boguniewicz M, Beck LA, Hanifin JM, Schneider LC, Hata TR, Gallo RL, Kaplan MH, Barnes KC, Leung DY. The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections. J Allergy Clin Immunol. 2011 Nov;128(5):1006-14. doi: 10.1016/j.jaci.2011.06.003. Epub 2011 Jul 18. |
| 20109744 | Result | Grigoryev DN, Howell MD, Watkins TN, Chen YC, Cheadle C, Boguniewicz M, Barnes KC, Leung DY. Vaccinia virus-specific molecular signature in atopic dermatitis skin. J Allergy Clin Immunol. 2010 Jan;125(1):153-159.e28. doi: 10.1016/j.jaci.2009.10.024. |
| Division of Allergy, Immunology, and Transplantation (DAIT) | View source |
ImmPort study identifier is SDY10. |
| SDY10 | Study Protocol | View IPD | ImmPort study identifier is SDY10. |
| SDY10 | Study design, -summary, -files; participant demographics, et al. | View IPD | ImmPort study identifier is SDY10. |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |