Immune Signature of Palmoplantar Pustulosis
| Status: | Completed |
|---|---|
| Conditions: | Psoriasis |
| Therapuetic Areas: | Dermatology / Plastic Surgery |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 5/5/2014 |
| Start Date: | June 2013 |
| End Date: | January 2015 |
| Contact: | Quinette Haynes |
| Email: | qhaynesresearch@gmail.com |
| Phone: | 214-379-0186 |
The Immune Signature of Palmoplantar Pustulosis
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.
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.
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.
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.
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.
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