Role of Chemokine and Chemokine Receptor in Psoriasis

Study Overview
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Brief Summary
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This study aims to elucidate the role of Chemokine and chemokine receptor in the pathogenesis of Psoriasis by using human psoriasis skin xenograft SCID mouse model. The hypothesis is that chemokine and chemokine receptor play important roles in psoriasis and establishment of human skin xenograft mouse model provide excellent platform to test the hypothesis.

Detailed Description
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Chemokines belongs to a large group of small chemotactic proteins (8-11 kilodaltons in size). Upon engagement of chemokine, chemokine receptor can activate downstream intracellular signaling pathways and results in diverse cellular processing such as cytoskeleton reorganization and cell locomotion. Chemokines are chemoattractant factors and can stimulate directional migration of all classes of leukocytes such as T cells. Epidermal keratinocytes in the skin are able to express multiple chemokines that can attract certain leukocytes, such as T cells or dendritic cells (DCs), to migrate to the epidermis. Psoriasis is a type of skin inflammatory diseases that results in misregulated immune system including immune cell infiltration. Keratinocyte secreted chemokine and chemokine receptor on leukocytes have been known to involve in the pathogenesis of psoriasis. However, it is not very clear how chemokines are regulated in keratinocytes and the binding of chemokine to receptor on leukocytes controls the pathogenesis of psoriasis. To better understand the immune regulation of chemokine and chemokine receptor in the molecular mechanism and pathogenesis of psoriasis, the investigators plan to establish human psoriasis skin xenograft mouse model that involves graft of human skin onto immune deficient mice. The human skin, including lesional and non-lesional skins, has been proven to be acceptable to the SCID mice and the phenotype can maintain for a number of months. The advantage of the xenograft model is to that it can preserve the full complexity of human diseases and thus resembles the pathogenesis of human diseases. This model has also been shown with constant efficacy of anti-psoriasis drug in comparison with clinical practice. Thus, this mouse model has great value to help the investigators understand how chemokine and immune cells are regulated in psoriasis. Of particular note is that this model can be used to test therapeutic drug before introduce them into clinical trial.

Official Title
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Role of Chemokine and Chemokine Receptor in Psoriasis

Conditions
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Psoriasis

Intervention / Treatment
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* Procedure: Shave Biopsy of Psoriasis Lesion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects 18 years of age or greater Subjects need to fulfill the diagnostic evidence of psoriasis with or without psoriatic arthritis Subject may take the following medicines: NSAID, hydroxychloroquine, sulfasalazine, prednisone (<10 mg/day), Methotrexate (10 mg/week) Subject needs to stop topical skin preparations other than emollients in one small plaque of psoriasis for 3-4 wks from where the shave biopsy will be taken Willing and able to provide informed consent in English Exclusion Criteria: Subjects less than 18 years old no clinical evidence of psoriatic skin Subjects with contraindications for biopsy, and patients receiving anticoagulants Subjects with active hepatitis B or Hepatitis C infection Subjects with concomitant inflammatory diseases such as inflammatory bowel disease, gout Subjects who are taking the following systemic biological therapies for psoriasis: cyclosporine, methotrexate, prednisone, acitretin, sulfasalazine, certolizumab, etanercept, adalimumab, infliximab, golimumab, secukinumab, ustekinumab, and apremilast. Other systemic medications may exclude the subject from the study.

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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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Biopsy of Skin with Psoriasis<br>Shave biopsy of psoriasis lesion | Procedure: Shave Biopsy of Psoriasis Lesion<br>* The investigator will take about 0.5x0.5 inch square section of skin from the psoriasis lesion. To numb the skin, the subject will receive a small injection of 0.5% lidocaine HCl 5mg/mL with 1:200,000 mcg/mL epinephrine solution as per standard shave biopsy protocol. The shaving instrument has a blade that will shave off a superficial piece of skin that is less than <3mm in thickness. After 14 days, the subject will return to make sure that the skin biopsy site has healed properly. The piece of skin that is removed will be grafted onto the back of an immunocompromised SCID mouse. An approved IACUC protocol covering this procedure will be in place prior to engraftment.<br>* Other names: injection, lidocaine HCl with epinephrine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acquisition of psoriatic skin from patient to transfer to immunocompromised mice | The purpose of this human clinical trial is to harvest psoriatic skin for engraftment onto immunocompromised mice. The primary outcome measure is to identify a 0.75 x 0.75 square inch piece of skin with psoriasis on study subjects to be biopsied. specific outcome measure that will be obtained in the patients other than ensuring that their graft sites heal appropriately. Their skin, once placed on immunocompromised mice, will be used to test new therapeutic drugs which might have a beneficial outcome in psoriasis, as measured in this mouse model. | Five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Observe Appropriate Healing in Subject Biopsy sites | The secondary outcome measure is to observe that study subjects' graft sites heal appropriately. | Five years |