JAK-STAT Signaling Pathway in Pyoderma Gangrenosum

Study Overview
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Brief Summary
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The investigators hypothese that Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway play a key role in pathophysiology of pyoderma gangrenosum (PG). In this study JAK/STAT signaling pathway will be investigated in the skin biopsies of PG patients

Detailed Description
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Cytokines are key molecules in the pathogenesis of inflammatory diseases. These molecules exert their effects through cell surface receptors and intracellular signaling pathways. Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway is implicated in the pathogenesis of several autoimmune diseases. Pyoderma gangrenosum (PG) is an inflammatory skin disease characterized by progressive and recurrent skin ulceration of destructive course. Treatment of PG requires aggressive immunosuppressive therapy but despite the use of several agents, including tumor necrosis factor inhibitory treatments there is still an unmet need in refractory PG. Recent reports suggested activation of JAK/STAT pathway in PG and some case-based studies suggested the beneficial effect of JAK-STAT inhibitory agent in the treatment of PG. Skin biopsies obtained from PG, hidradenitis suppurativa, psoriasis and healthy subjects will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods. The following immunohistochemical stains will be used to evaluate the expression of JAK/STAT pathway: JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6. Staining intensity will be recorded categorically (negative and positive). The positive staining will also be graded semi-quantitively as follows: mildly positive, moderately positive and strongly positive.

Official Title
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Expression of the JAK-STAT Signaling Pathway in Pyoderma Gangrenosum Pathological Biopsy

Conditions
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Pyoderma Gangrenosum, Hidradenitis Suppurativa, Psoriasis

Intervention / Treatment
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* Diagnostic Test: immunohistochemical methods


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pyoderma gangrenosum diagnosed with skin biopsy Psoriasis diagnosed with skin biopsy Hidradenitis suppurativa diagnosed with skin biopsy Skin biopsy in healthy subjects Exclusion Criteria: - This is a case-based study and there is no exclusion criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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 |
| --- | --- |
| Pyoderma Gangrenosum<br>Skin biopsies obtained from patients with pyoderma gangrenosum will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods. | Diagnostic Test: immunohistochemical methods<br>* The following immunohistochemical stains will be used to evaluate the expression of JAK/STAT pathway: JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6. Staining intensity will be recorded categorically (negative and positive). The positive staining will also be graded semi-quantitively as follows: mildly positive, moderately positive and strongly positive.<br>|
| Hidradenitis Suppurativa<br>Skin biopsies obtained from patients with hidradenitis suppurativa, will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods | Diagnostic Test: immunohistochemical methods<br>* The following immunohistochemical stains will be used to evaluate the expression of JAK/STAT pathway: JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6. Staining intensity will be recorded categorically (negative and positive). The positive staining will also be graded semi-quantitively as follows: mildly positive, moderately positive and strongly positive.<br>|
| Psoriasis<br>Skin biopsies obtained from patients with psoriasis, will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods | Diagnostic Test: immunohistochemical methods<br>* The following immunohistochemical stains will be used to evaluate the expression of JAK/STAT pathway: JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6. Staining intensity will be recorded categorically (negative and positive). The positive staining will also be graded semi-quantitively as follows: mildly positive, moderately positive and strongly positive.<br>|
| Healthy Subjects<br>Skin biopsies obtained from patients with healthy subjects, will be used to control group. | Diagnostic Test: immunohistochemical methods<br>* The following immunohistochemical stains will be used to evaluate the expression of JAK/STAT pathway: JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6. Staining intensity will be recorded categorically (negative and positive). The positive staining will also be graded semi-quantitively as follows: mildly positive, moderately positive and strongly positive.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Expression of JAK-STAT pathway | Expression of JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6 in tissue levels in PG. | 15 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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JAK-STAT pathway, Pyoderma Gangrenosum, Skin Biopsy