In the present project we would like to find out whether we can observe Treg into Th17 conversion in lesional skin and in the peripheral blood of patients with AD and compare the results to our findings in psoriatic patients and healthy controls.…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Skin biopsies are processed and tissue sections will be analyzed for the
presence of IL-17-producing Treg using multicolour immunohistochemestry and
multicolour immunofluorescence. Tissues will be visualized using microscopy,
photographed and analysed using computer software. From the peripheral blood we
will isolate CD4+CD25+Treg cells and look whether they have the propensity to
differentiate and to produce cytokines upon ex vitro stimulation.
Secondary outcome
We will also look for several other surface differentiation markers, T
lineage-specific transcription factors and cytokines.
Background summary
Atopic dermatitis (AD) and psoriasis are both chronic inflammatory skin
diseases which result from a complex interaction between genetic components and
environmental influences. In both skin diseases, deregulation of the immune
system plays an important role in the pathogenesis. In this project we will
focus on several T-cell subsets that we already saw in psoriasis. We would like
to address whether these T cell subsets are also present in AD and compare the
results to psoriatic patients and healthy controls. More specific we will focus
on regulatory T-cells (Tregs) and Thelper-17 cells (Th17). Tregs are important
in the *off-switch* of inflammation, and are characterised by the expression of
CD25 and transcription factor Foxp3. Impaired functioning of these cells is
considered in the context of several auto-immune inflammatory diseases. In
contrast, Th-17 cells are important in the *on-switch* of inflammation, and are
characterised by the expression of transcription factor RORγt and the
production of IL-17. Recent findings demonstrate that under pro-inflammatory
conditions Tregs can differentiate in vitro into inflammation associated
IL-17-producing cells. This conversion is also seen skin and peripheral blood
derived-Tregs from severe psoriasis patients. Moreover, there are indications
that Th17 cells also play an important role in the pathogenesis of atopic
dermatitis.
Study objective
In the present project we would like to find out whether we can observe Treg
into Th17 conversion in lesional skin and in the peripheral blood of patients
with AD and compare the results to our findings in psoriatic patients and
healthy controls. Furthermore, we are interested in several other lymphocyte
subsets, T lineage-specific transcription factors and cytokines that might
contribute to the process of inflammation in these skin conditions.
Study design
This is an explorative observational study in order to assess Treg into Th17
conversion in AD versus psoriasis. We will demonstrate this by analysing
peripheral blood (100 ml) and a 4 mm skin biopsiy from each volunteer.
Study burden and risks
All volunteers have to sign an informed consent paper before entering the
study. On their first and only visit we will obtain a punch biopsy of the skin
and peripheral blood. Punch biopsies and venapunctures are taken according to
standard procedure and may be slightly tender. Scar formation after biopsies
does not occur or is barely visible. Venapunctures can lead to the formation of
a small and self-limiting haematoma. The study-visit is extra. After the
interventions, the volunteers are released from follow-up. Participating in
this study does not lead to direct benefit for the volunteers. Participation
will not interfere with the preferred medical care that is given to the
patient.
Postbus 9101
6500 HB Nijmegen
NL
Postbus 9101
6500 HB Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Patients with atopic dermatitis must meet the following criteria:
• Adults older than 18 years of age
• Patients with moderate to severe atopic dermatitis (TIS score >=3)
• Patients must be willing to give a written informed consent
• Patients must be able to adhere to the visit schedule ;Patients with psoriatis must meet the following criteria:
• Adults older than 18 years of age
• Patients with severe psoriasis (PASI >=15)
• Patients must be willing to give a written informed consent
• Patients must be able to adhere to the visit schedule ;Healthy volunteers must meet the following criteria:
• Adults older than 18 years of age
• Volunteers must be willing to give a written informed consent
• Volunteers must be able to adhere to the visit schedule
Exclusion criteria
Patients with atopic dermatitis will be excluded from this study when any of the following criteria listed below are met:
• Children or adolescents younger than 18 years of age
• Patients with, besides atopic dermatitis, psoriasis
• Patients that use systemic medication for their atopic dermatitis, for
example ciclosporine
• Patients who are currently treated with phototherapy
• Patients with mild atopic dermatitis
• Patients using trial medication
• Patients using immunosuppressive agents like prednisone or methotrexate
• Patients with relevant co-morbidities
• Patients with a current condition involving an activated immune system,
such as the flue or a recent vaccination;Patients with psoriasis will be excluded from this study when any of the following criteria listed below are met:
• Children or adolescents younger than 18 years of age
• Patients with, besides psoriasis, atopic dermatitis
• Patients that use systemic medication for their psoriasis, for
example acitretin or biologics
• Patients who are currently treated with phototherapy
• Patients with a mild to moderate psoriasis (Psoriasis Area and Severity
Index <=15)
• Patients using trial medication
• Patients using immunosuppressive agents like prednisone or methotrexate
• Patients with relevant co-morbidities
• Patients with a current condition involving an activated immune system,
such as the flue or a recent vaccination
The healthy volunteer will be excluded from this study when any of the following criteria listed below are met:
• Children or adolescents younger than 18 years of age
• A volunteer with a history or signs of a relevant skin disease
• A volunteer with a family history of atopic dermatitis or psoriasis
• Volunteers using immunosuppressive agents like prednisone or methotrexate
• Volunteers with relevant co-morbidities
• Volunteers with a current condition involving an activated immune system,
such as the flue or a recent vaccination
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL37430.091.11 |