Clinical trial NCT01538342: Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis
Official title: Role of Tyrosine Kinase Lyn and Cleaved Form by Caspases in Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Psoriasis
Atopic Dermatitis
Lead sponsor: Centre Hospitalier Universitaire de Nice
Sponsor class: OTHER
First posted: 2012-02-24
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.


Eligibility 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.

Primary outcomes:
measure: Cleavage of Lyn
timeFrame: 1 day
measure: Expression levels of Lyn
timeFrame: 1 day
measure: Specific activity of apoptotic caspases 3, 6, 7, 8 and 9, and inflammatory caspases 1, 4, and 5
timeFrame: 1 day
Secondary outcomes:
measure: Development of a monoclonal antibodyspecific for the cleaved form of caspases by Lyn
timeFrame: 1 day
Other outcomes:
Locations:
city: Marseille
country: France
facility: Assistance Publique - Hôpitaux de Marseille
city: Nice
country: France
facility: University Hospital of Nice
city: Toulouse
country: France
facility: University Hospital of Toulouse
Study officials:
affiliation: Centre Hospitalier Universitaire de Nice
name: Jean-Paul ORTONNE, PU-PH
role: STUDY_DIRECTOR
affiliation: Institut National de la Santé Et de la Recherche Médicale, France
name: Sandrine MARCHETTI, PhD
role: STUDY_CHAIR
affiliation: AP-HM
name: Marie-Aleth RICHARD, PU-PH
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Toulouse
name: Carle PAUL, PU-PH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aira LE, Goncalves D, Bossowski JP, Rubio-Patino C, Chiche J, Paul-Bellon R, Mondragon L, Gesson M, Lecucq-Ottavi P, Obba S, Colosetti P, Luciano F, Bailly-Maitre B, Boyer L, Jacquel A, Robert G, Ricci JE, Ortonne JP, Passeron T, Lacour JP, Auberger P, Marchetti S. Caspase 1/11 Deficiency or Pharmacological Inhibition Mitigates Psoriasis-Like Phenotype in Mice. J Invest Dermatol. 2019 Jun;139(6):1306-1317. doi: 10.1016/j.jid.2018.11.031. Epub 2018 Dec 17.