Our primary objectives are to analyse the gene expression profile of non-lesional and lesional skin of patients with NS (ichthyosis linearis circumflexa (ILC) phenotype and scaly erythroderma (SE) phenotype) using single cell RNA sequencing and…
ID
Source
Brief title
Condition
- Epidermal and dermal conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameters are the difference in gene expression profile of skin
(lesional and non-lesional) of patients with NS (using scRNA-seq, and spatial
transcriptomics) from skin of healthy controls and the difference in gene
expression profile of NS-ILC and NS-SE. Furthermore, lesional NS skin will be
compared with lesional AD skin and lesional psoriasis skin.
Secondary outcome
Secondary endpoints of this study are:
- Comparison of the gene expression profile (using scRNA-seq and spatial
transcriptomics) in the lesional skin of NS patients with lesional skin in AD,
and lesional skin in psoriasis
- Comparison of the expression profile using scRNA-seq and spatial
transcriptomics with bulk-RNA sequencing in and between all previously
mentioned subgroups (lesional NS, non-lesional NS, ILC-NS, SE-NS, lesional AD,
lesional psoriasis, and healthy controls).
- Comparison of the gene expression profile with immunohistochemistry in the
skin of NS, AD, psoriasis, and healthy control skin and to compare
immunohistochemical differences amongst subgroups.
- Correlation of the knowledge on the skin inflammation signature of NS with
the systemic inflammation signature, analyzed by measured serum cytokine levels
and phenotyping of peripheral blood immune cells (PBMCs) compared to psoriasis,
AD, and healthy controls.
Background summary
Netherton syndrome (OMIM #256500) (NS) is a rare genetic disorder caused by an
autosomal recessive mutation in the serine peptidase inhibitor, Kazal type 5
(SPINK5) gene. Although Netherton is a severe skin disease, sometimes even
life-threatening, little is known about therapeutic options and their outcomes,
with treatment regimens being only supportive in nature. Lifelong treatment is
required, but there are no registered treatments and treatment guidelines
available for patients with NS. This is partly due to the fact that the
pathogenesis of NS is not yet fully understood. In previous studies, the
transcriptomic signature of NS has been investigated using RT-PCR and bulk RNA
sequencing. In contrast to these techniques, single cell RNA sequencing
(scRNA-seq) and spatial transcriptomics give a more precise understanding of
the transcriptome in individual cells and will enable us to map the location of
gene activity in the skin. These insights can help to identify potential
targets for treatment in NS patients.
Study objective
Our primary objectives are to analyse the gene expression profile of
non-lesional and lesional skin of patients with NS (ichthyosis linearis
circumflexa (ILC) phenotype and scaly erythroderma (SE) phenotype) using single
cell RNA sequencing and spatial transcriptomics, compared to skin of healthy
controls. Furthermore, lesional NS skin will be compared with lesional atopic
dermatitis (AD) skin and lesional psoriasis skin because of the clinical and
the pathophysiological resemblances.
Study design
Multicenter study with an explorative study design. Patients will be included
both in France and the Netherlands.
Study burden and risks
The samples will be collected at one time point. A skin excision is a routine
dermatological procedure and is generally safe, however there is a small risk
of bleeding and infection. Furthermore, the elliptic excision will leave a
small linear scar. Blood drawing is a routine clinical procedure and is
generally safe, besides the risk of a local hematoma after blood collection.
The participants will not directly benefit from this research, but
participation contributes to increasing knowledge about NS, and subsequently
improving treatment and care for NS patients. Furthermore, comparison of the
gene expression in lesional skin in three different skin diseases (NS,
psoriasis, atopic dermatitis) contributes to our knowledge about differences
and similarities in these diseases.
Wytemaweg 80
Rotterdam 3015 CN
NL
Wytemaweg 80
Rotterdam 3015 CN
NL
Listed location countries
Age
Inclusion criteria
Patients with Netherton syndrome:
- A genetic diagnosis of Netherton syndrome
- Aged 18 years or above (adult)
Patients with atopic dermatitis (AD):
- Aged 18 years or above (adult)
- Dermatologist diagnosed atopic dermatitis (AD)
- AD lesion of at least 25x6mm
Patients with psoriasis:
- Aged 18 years or above (adult)
- Dermatologist diagnosed psoriasis
- Psoriasis lesion of at least 25x6mm
Exclusion criteria
Exclusion criteria for Netherton syndrome (NS) patients, atopic dermatitis (AD)
patients, and psoriasis patients:
- Use of systemic treatment within a period of 5 half-lives (in the past week
to ~3 months depending on the type of medication)
- Bathing within 24-hours prior to the skin excision
- Application of a topical medication (e.g. topical corticosteroids, topical
calcineurin inhibitors, topical antibiotics) within 1 week before skin excision
- Active (haematological) malignancy
- Pregnancy or breastfeeding
- No skin lesion of 25x6mm on either trunk or extremities (arms, legs)
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 | NL81941.078.22 |