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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Psoriasis; Atopic Dermatitis	Other: 3 Biopsies; Other: 2 biopsies; Other: biopsy	Not Applicable

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	170 participants
Allocation:	Non-Randomized
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis
Study Start Date :	July 2012
Estimated Primary Completion Date :	July 2016
Estimated Study Completion Date :	July 2016

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
chronic plaque psoriasis; 3 biopsies: 2 lesional and 1 non-lesional	Other: 3 Biopsies; 3 biopsies: 2 lesional and 1 non-lesional
pustular psoriasis; 3 biopsies: 2 lesional and 1 non-lesional	Other: 3 Biopsies; 3 biopsies: 2 lesional and 1 non-lesional
erythrodermic psoriasis; 3 biopsies: 2 lesional and 1 non-lesional	Other: 3 Biopsies; 3 biopsies: 2 lesional and 1 non-lesional
atopic dermatitis; 2 biopsies: 1 lesional and 1 non-lesional	Other: 2 biopsies; Other Name: 1 lesional and 1 non-lesional
healthy patients; 1 biopsy of healthy skin.	Other: biopsy; 1 biopsy ok healthy skin

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Cleavage of Lyn [ Time Frame: 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.
2. Expression levels of Lyn [ Time Frame: 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).
3. Specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5 [ Time Frame: 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.

Secondary Outcome Measures :

1. Development of a monoclonal antibodyspecific for the cleaved form of caspases by Lyn [ Time Frame: 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.

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Jean-Paul ORTONNE, PU-PH	04 92 03 64 88 ext +33	ortonne@unice.fr
Contact: Sandrine MARCHETTI, PhD	04 93 37 70 16 ext +33	Sandrine.Marchetti@unice.fr

Locations

France
Assistance Publique - Hôpitaux de Marseille	Recruiting
Marseille, France, 13 005
Contact: Marie-Aleth RICHARD, PU-PH 04 91 38 79 91 ext +33 mrichard@ap-hm.fr
Principal Investigator: Marie-Aleth RICHARD, PU-PH
University Hospital of Nice	Active, not recruiting
Nice, France, 06000
University Hospital of Toulouse	Not yet recruiting
Toulouse, France, 31059
Contact: Carle PAUL, PU-PH 05 61 77 76 75 ext +33 paul.c@chu-toulouse.fr
Principal Investigator: Carle PAUL, PU-PH

Sponsors and Collaborators

Centre Hospitalier Universitaire de Nice

Investigators

Study Director:	Jean-Paul ORTONNE, PU-PH	CHU de Nice
Study Chair:	Sandrine MARCHETTI, PhD	Institut National de la Santé Et de la Recherche Médicale, France
Principal Investigator:	Marie-Aleth RICHARD, PU-PH	AP-HM
Principal Investigator:	Carle PAUL, PU-PH	University Hospital, Toulouse

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

Recent developments in the understanding of the pathogenesis of psoriasis 

Responsible Party:	Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:	NCT01538342 History of Changes
Other Study ID Numbers:	11-API-03
First Posted:	February 24, 2012
Last Update Posted:	April 25, 2016
Last Verified:	April 2016

Additional relevant MeSH terms:

Psoriasis; Dermatitis; Dermatitis, Atopic; Eczema; Skin Diseases, Papulosquamous; Skin Diseases	Skin Diseases, Genetic; Genetic Diseases, Inborn; Skin Diseases, Eczematous; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases