Characterization and Functionality of Calcium Channels Cav1.4 of Th17 Lymphocytes in Human With Psoriasis

Study Overview
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Brief Summary
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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
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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

Official Title
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Characterization and Functionality of Calcium Channels Cav1.4 of Th17 Lymphocytes in Human With Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Biological: Skin biopsies
* Biological: Blood sample


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 : 20 subjects with plaque psoriasis<br>Intervention: skin biopsies and blood sample | Biological: Skin biopsies<br>* 3 biopsies on lesion skin (and one more for the first fifteen subjects in group 1)<br>Biological: Blood sample<br>* One blood sample for the group 1 only.<br>|
| Experimental: Group 2 : 10 subjects with atopic dermatitis<br>Intervention: skin biopsies | Biological: Skin biopsies<br>* 3 biopsies on lesion skin (and one more for the first fifteen subjects in group 1)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of Cav1.4 calcium channels in Th17 lymphocytes | Immunohistochemistry (IHC) and in situ hybridation (HIS) | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Role of Cav1.4 channels on the activation of Th17 lymphocytes | Fonctional study : intracellular marquing and qPCR (with TLDA technology (TaqMan Low Density Arrrays)) and ELISA method | Baseline | 
| Transcriptomic signature relating to the signaling channel Cav1.4 | qPCR with TLDA technology (TaqMan Low Density Arrrays) | Baseline | 
| Epigenetic signature, in particular changes in overall methylation and specific promoter methylation | Pyrosequencing | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Th17, Cav1.4, Lymphocyte, Channel