Psoriasis
Conditions
Keywords
Th17, Cav1.4, Lymphocyte, Channel
Brief summary
It's clearly known that lymphocyte activation in particular Th17 response, plays a major role in the development of plaque psoriasis. New therapies targeting this pathway are showing great clinical efficacy in patients with moderate to severe plaque psoriasis. Pioneering observations have shown that the expression of Cav1.4 channels in Th17 lymphocytes and they're functional role is supported by the inhibition of IL-17 production by a pharmacological inhibitor of Cav1 channels that is effective in a mouse model of Psoriasis. This data strongly suggest that the Cav1.4 channel, via its involvement in the signalling responsible for the production of Th17 cytokines represents an interesting therapeutic target in Psoriasis. The aim of the study is to explore biological functions related to the activation of the Cav1.4 pathway in Psoriasis.
Detailed description
* Evaluate the expression of Cav1.4 calcium channels by Th17 lymphocytes from plaque psoriasis. * To assess: * The role of Cav1.4 channels on the activation of Th17 lymphocytes * The transcriptomic signature relating to the signalling channel Cav1.4 * The epigenetic signature, in particular changes in overall methylation and specific promoter methylation
Interventions
BIOLOGICALSkin biopsies
3 biopsies on lesion skin (and one more for the first fifteen subjects in group 1)
BIOLOGICALBlood sample
One blood sample for the group 1 only.
Sponsors
Centre National de la Recherche Scientifique, France
Institut National de la Santé Et de la Recherche Médicale, France
Pierre Fabre Dermo Cosmetique
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Monocentric, open-label, comparative, parallel group and intra-individual patho-physiological study : * Group 1 : 20 subjects with plaque psoriasis * Group 2 : 10 subject with atopic dermatitis
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Group 1 : Subject with plaque psoriasis (diagnosis confirmed by dermatologist) with a plaque IGA score ≥ 3 * Group 2 : Subject with atopic dermatitis according to the UK Working party criteria with an IGA plaque score ≥3 Exlusion Criteria: * Group 1 : Other chronic inflammatory dermatosis than plaque psoriasis at the sites to be sampled * Group 2 : Other chronic inflammatory dermatosis than Atopic Dermatitis at the sites to be sampled * For both groups: Ongoing treatment with calcium channel blockers * For both groups: Any current topical treatment on the biopsied or systemic plaque for psoriasis or AD (including phototherapy)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression of Cav1.4 calcium channels in Th17 lymphocytes | Baseline | Immunohistochemistry (IHC) and in situ hybridation (HIS) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Role of Cav1.4 channels on the activation of Th17 lymphocytes | Baseline | Fonctional study : intracellular marquing and qPCR (with TLDA technology (TaqMan Low Density Arrrays)) and ELISA method |
| Transcriptomic signature relating to the signaling channel Cav1.4 | Baseline | qPCR with TLDA technology (TaqMan Low Density Arrrays) |
| Epigenetic signature, in particular changes in overall methylation and specific promoter methylation | Baseline | Pyrosequencing |
Countries
France
Outcome results
None listed