Immune Signature of Palmoplantar Pustulosis

Study Overview
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Brief Summary
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This study is being done to learn more about a less common type of psoriasis, called palmoplantar pustulosis (PPP). The majority of the current treatments used for this type of psoriasis have only a moderate effect on PPP. Thus, the investigators believe that PPP may be a different disease entity altogether, requiring different therapies. As such, the investigators hope to discover an immune signature for this condition. An immune signature is the unique way in which the combination of genes, cells, and proteins of the immune system work for each person. Because both psoriasis and the type of psoriasis patients have been diagnosed with, PPP, are conditions of abnormal immune system function, it is important to understand the overall function of the immune system in this condition (that is, find the immune signature). This study should help identify an immune system signature in people with PPP. The investigators have a laboratory technology which allows them to read the genetic signatures of a person's blood cells. Genes contain the instructions for making living things. Genes are contained in the cells' DNA (deoxyribonucleic acid). Most DNA is the same among humans, but the small differences people have in their DNA may explain why people develop different diseases. DNA and the genes it contains help produce RNA (ribonucleic acid), which in turn helps make proteins in people's cells. Differences in the types of proteins and the amount of those different proteins people's cells produce can affect a person's immune system. To help the investigators determine the immune signature in PPP, they will be examining the different genes, cells, and proteins that are active in patients with PPP versus patients who do not have the condition. The investigators will examine these genes, cells, and proteins in skin (through a skin sample) and in blood (through a blood draw). The goal is to develop new treatments for this skin condition. To do this, the investigators need to compare the skin and blood of patients with this particular type of psoriasis to the samples of healthy patients.

Detailed Description
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I. SPECIFIC AIM Specific Aim. To identify transcriptional signatures in the skin and blood of patients with palmoplantar pustulosis (PPP). II. BACKGROUND AND SIGNIFICANCE Despite major advances in elucidating the molecular pathways of chronic plaque psoriasis (CPP), the immunopathogenesis of PPP, a less common variant of psoriasis, remains elusive. It is characterized by the development of inflammatory sterile pustules on the palms and soles of affected individuals, which can be exceptionally painful, interfering with walking and manual activities and impinging significantly on quality of life. Current systemic and biologic treatments used to treat CPP have only a moderate effect in patients with PPP, supporting the suggestion that PPP is a separate disease entity with a distinct immunopathogenic basis. Moreover, the spontaneous paradoxical development of PPP is frequently observed in patients treated with anti-tumor necrosis factor-α therapies, agents typically used in the treatment of CPP. Genetic analysis also distinguishes patients with PPP from those with CPP. At the investigators' institution, microarray analyses of blood transcriptional patterns have permitted crucial advances in characterizing the immunopathogenesis of immune-mediated conditions such as systemic lupus erythematosis and systemic-onset juvenile idiopathic arthritis. The investigators now wish to examine transcriptional profiles in the skin and blood of patients with PPP to identify the immunopathogenesis of this condition and identify potential therapeutic targets. The investigators will validate the findings at a cellular and protein level using flow cytometry, immunohistochemistry and measuring serum levels of proteins in the blood with Luminex or ELISA.

Official Title
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The Immune Signature of Palmoplantar Pustulosis

Conditions
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Palmoplantar Pustulosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must give written informed consent. Subjects are age 18 years or older, with a diagnosis of palmoplantar pustulosis (PPP) or be a healthy control. Subjects must be able to adhere to the study visit schedule and other protocol requirements. Patient must be off systemic psoriasis therapies (e.g. retinoids, phototherapy, methotrexate, cyclosporine etc.) for at least 4 weeks, biologic therapies for 12 weeks (or 24 weeks in the case of ustekinumab) and off topical therapies (e.g. calcipotriene, topical steroids) for at least 2 weeks. Exclusion Criteria: Inability to provide informed consent. Patient is unwilling to be off systemic psoriasis therapies for at least 4 weeks, biologic therapies for 12 weeks (or 24 weeks in the case of ustekinumab) or off topical therapies for at least 2 weeks. Unwilling to consent to skin biopsy or blood draw. Are pregnant, nursing, or planning a pregnancy while enrolled in the study. Uncontrolled medical conditions (diabetes, liver disease, renal disease). Have a history of latent or active granulomatous infection, including histoplasmosis or coccidioidomycosis, prior to screening or have had a non-tuberculous mycobacterial infection or opportunistic infection (e.g., cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| PPP patients<br>Patients with palmoplantar pustulosis who have had blood and tissue samples taken. | |
| Healthy controls<br>Patients without palmoplantar pustulosis or any inflammatory skin condition who have had blood and tissue samples taken. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gene expression profiles | To assess gene expression profiles in the skin and blood of patients with palmoplantar pustulosis compared with those of healthy controls. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine leukocyte subsets in PPP | To examine leukocyte subsets in the blood of patients with palmoplantar pustulosis compared to healthy controls. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palmoplantar pustulosis, psoriasis