This is a pilot study with the objective of studying the effect of vaselin on TSLP expression in nonlesional human AD skin.
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
In vivo: TSLP mRNA expression level (qPCR or quantitative Polymerase Chain
Reaction) in cryosections from skin biopsy material (quantitative).
Secondary outcome
Immunohistochemical staining for TSLP protein and other related products in
cryosections from skin biopsy material (qualitative; determining presence and
localization).
Background summary
Atopic dermatitis (AD) is an atopic chronic inflammatory skin disease, usually
characterised by high levels of circulating IgE and infiltration of skin
lesions by immune cells that express a predominant Th2 cytokine pattern. This
infiltration with immune cells is much less outside the skin lesions. However,
the presence of immune cells in the nonlesional skin makes it immunologically
'pre-activated' compared to healthy control skin. Recently a cytokine called
thymic stromal lymphopoietin (TSLP) was discovered that is produced by
keratinocytes and seems to play an early role in the induction of allergic
inflammation in the skin, both in mice and in humans. In humans, TSLP is
detected only in lesional but not in nonlesional AD skin. In healthy human
skin, TSLP expression can be induced ex vivo, by allergens, cytokines,
micro-organisms and trauma.
Still, little is known about the factors that trigger TSLP expression by
keratinocytes in human AD skin or the kinetics thereof.
The atopy patch test (APT) is a human in vivo model for atopic dermatitis.
During the APT an allergen (e.g. house dust mite) is patched onto the skin for
24-48 hours, resulting in an eczematous reaction, which is very similar to
lesional AD. We have recently shown house dust mite induced expression of TSLP
in APT (manuscript in preparation). Some patients had a negative APT during the
study, despite an initial positive test during screening. In biopsies from
these negative APTs, we did find increased TSLP gene expression, but no TSLP
protein expression. This suggests that patch testing in these patients induced
activation of the TSLP pathway independent of the allergen activity. Insight
into the mechanisms of vaselin (solvent) patch test on TSLP expression will
enable a better controlled interpretation of previous study (protocolnr
NL32336.041.10) results, as well as better future interpretation of APT-induced
lesional AD skin model results. This is a pilot study with the objective of
studying the effect of vaselin patch test on TSLP expression in nonlesional AD
skin.
Study objective
This is a pilot study with the objective of studying the effect of vaselin on
TSLP expression in nonlesional human AD skin.
Study design
This is a pilot study.
The effect of vaselin on TSLP expression in human nonlesional AD skin (n=5).
a. Biopsies from nonlesional skin (1 biopsy) and 48 hours (1 biopsy) after
patch test with vaselin only.
b. TSLP mRNA (qPCR) levels measured in biopsy material. Localization of TSLP
expression and other related products (immunohistochemistry) in biopsy
sections.
Study burden and risks
Participants will undergo an APT and two skin punch biopsies (4mm diameter) in
two sessions. The specified number of biopsies is necessary to carry out
sufficient controls. Only the 48 hour time point is chosen for biopsying, to
enable TSLP protein detection (as well as TSLP mRNA detection) to ascertain a
possible effect and at the same time reduce the number of biopsies as much as
possible.
The specified amount of material is necessary to perform the described
analyses. There is no direct benefit for participants. Performing a biopsy
entails a slight risk of haemorrhage and infection. A small scar at the site of
biopsy will gradually fade in colour. An APT will induce erythema and pruritus
with sometimes papules, vesicles and blisters. The reaction disappears after
72-96 hours.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
age 18-70 years
AD
positive APT during previous study (NL32336.041.10 or 10-161 METC UMCU) and local TSLP mRNA (qPCR) and protein expression (immunohistochemistry) detectable in skinbiopsy material from testsite.
Exclusion criteria
- Active AD on the back
- LSS >30
- Not sensitized to aeroallergens, such as house dust mite (demonstrated by a positive Immuno CAP test for these allergens).
- Treatment with systemic corticosteroid or other immunosuppressive medication (such as cyclosporin) within the 4 weeks prior to having the biopsies performed. In addition, weekly use of equal or more than 50 grams of topical corticosteroids class IV or weekly use of equal or more than 100 grams of topical corticosteroids class III.
- Treatment of the biopsy and APT regions not restricted to indifferent topical treatment in the 2 weeks prior
- Exposure of biopsy location to UV sunlicht (e.g. UV-therapy, sunny holiday) in the 2 weeks prior to taking biopsies.
- Use of coumarin derivatives
- Use of antihistamines in the week or days before and during the APT (see patientinformation 'Bijlage 4: Medicatielijst').
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 | NL41110.041.12 |