Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis

Study Overview
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Brief Summary
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Psoriasis is a chronic autoimmune disorder of the skin. In this disease, the inflammatory caspases, cysteine proteases involved in the processing of many proteins, are activated. Transgenic mice expressing the cleaved form of caspases by Lyn, a tyrosine kinase Src family, develop an inflammatory syndrome with the characteristics of human psoriasis. To clarify the relationship between the cleaved form of Lyn by caspases and psoriasis, the investigators intend to develop a clinical study to analyze the expression, cleavage and activity of Lyn and the activation of caspases from skin biopsies of patients with this disease. This study will be conducted on a cohort of patients with different forms of psoriasis (plaque, pustular and erythrodermic) and atopic dermatitis, another skin disorder associated with chronic inflammation. Thus, the investigators will evaluate the expression and activity of Lyn from skin lesion (L) and non-lesional (NL) from the same patient in parallel with the level of caspase activation and apoptotic inflammatory. Thus, the investigators will verify that the cleavage by caspases of Lyn is associated specifically with psoriasis, as the investigators believe, or more generally to the skin inflammation. The investigators work would then define the cleavage by caspases of Lyn as a new potential marker of human psoriasis.

Official Title
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Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis

Conditions
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Psoriasis, Atopic Dermatitis

Intervention / Treatment
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* Other: 3 Biopsies
* Other: 2 biopsies
* Other: biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Psoriasis arms: Plaque psoriasis and erythrodermic more than 10% of body surface area. Pustular psoriasis of at least 1% of body surface. Atopic dermatitis arm:Patients with atopic dermatitis has been identified and inflammatory lesions on the skin. Healthy arm:People not suffering from any skin disease Exclusion Criteria: Systemic treatment of psoriasis for at least 4 weeks and / or local treatment for at least 2 weeks at the time of study entry. Patient with significant infection and / or immunocompromised.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: chronic plaque psoriasis<br>3 biopsies: 2 lesional and 1 non-lesional | Other: 3 Biopsies<br>* 3 biopsies: 2 lesional and 1 non-lesional<br>|
| Other: pustular psoriasis<br>3 biopsies: 2 lesional and 1 non-lesional | Other: 3 Biopsies<br>* 3 biopsies: 2 lesional and 1 non-lesional<br>|
| Other: erythrodermic psoriasis<br>3 biopsies: 2 lesional and 1 non-lesional | Other: 3 Biopsies<br>* 3 biopsies: 2 lesional and 1 non-lesional<br>|
| Other: atopic dermatitis<br>2 biopsies: 1 lesional and 1 non-lesional | Other: 2 biopsies<br> <br> * Other names: 1 lesional and 1 non-lesional;|
| Other: healthy patients<br>1 biopsy of healthy skin. | Other: biopsy<br>* 1 biopsy ok healthy skin<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cleavage of Lyn | The cleavage of Lyn will be determined in the different extracts of skin of patients with western blotting using an antibody specific for Lyn recognizing the native form but also the form cleaved by caspases. | 1 day | 
| Expression levels of Lyn | The expression levels of Lyn and its cleaved form will be quantified using the software MultiGauge. The investigators will also determine the level of activity of Lyn using an antibody directed against the active form phosphorylated. The level of expression of proteins of interest will be reported at the level of protein expression control (ERK2) whose expression does not vary depending on the samples (load control). | 1 day | 
| Specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5 | The investigators will determine the specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5 test microplate. The principle of this test is based on the use of a specific substrate of caspases coupled to a fluorochrome that fluoresces when it is released after the action of caspase-level target aspartate. The fluorescence emission, which is proportional to the amount of active caspase in the sample is then measured with a fluorometer. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Development of a monoclonal antibodyspecific for the cleaved form of caspases by Lyn | Development of a monoclonal antibody specific for the form cleaved by caspases of Lyn. Once obtained and validated, this tool will be especially useful for immunohistological analysis of Lyn on skin sections from patients with psoriasis. Then we can also analyze which skin cells express preferentially cleaved form of Lyn. | 1 day |