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

Not Applicable

Completed

• Conditions: Atopic Dermatitis; Psoriasis
• Interventions: Other: 3 Biopsies; Other: biopsy; Other: 2 biopsies

• Registration Number: NCT01538342
• Lead Sponsor: Centre Hospitalier Universitaire de Nice

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-01-13
• Study First Submitted QC: 2012-02-23
• Study First Posted: 2012-02-24
• Study Start: 2012-07
• Primary Completion: 2016-07
• Study Completion: 2016-07
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-05
• Last Update Posted: 2023-09-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 170

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
pustular psoriasis	3 Biopsies	3 biopsies: 2 lesional and 1 non-lesional
healthy patients	biopsy	1 biopsy of healthy skin.
erythrodermic psoriasis	3 Biopsies	3 biopsies: 2 lesional and 1 non-lesional
chronic plaque psoriasis	3 Biopsies	3 biopsies: 2 lesional and 1 non-lesional
atopic dermatitis	2 biopsies	2 biopsies: 1 lesional and 1 non-lesional

Primary Outcome Measures

Name	Time	Method
Cleavage of Lyn	1 day	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.
Specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5	1 day	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.
Expression levels of Lyn	1 day	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).

Secondary Outcome Measures

Name	Time	Method
Development of a monoclonal antibodyspecific for the cleaved form of caspases by Lyn	1 day	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.

Trial Locations

Locations (3)

University Hospital of Nice; 🇫🇷 Nice, France

Assistance Publique - Hôpitaux de Marseille; 🇫🇷 Marseille, France

University Hospital of Toulouse; 🇫🇷 Toulouse, France