JAK-STAT Signaling Pathway in Pyoderma Gangrenosum

Sponsor

Dokuz Eylul University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04792957

Collaborator

(none)

120

Enrollment

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pyoderma Gangrenosum Hidradenitis Suppurativa Psoriasis	Diagnostic Test: immunohistochemical methods

Detailed Description

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

120 participants

Observational Model:

Case-Only

Time Perspective:

Prospective

Official Title:

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

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Jul 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Pyoderma Gangrenosum Skin biopsies obtained from patients with pyoderma gangrenosum will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods.	Diagnostic Test: 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.
Hidradenitis Suppurativa Skin biopsies obtained from patients with hidradenitis suppurativa, will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods	Diagnostic Test: 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.
Psoriasis Skin biopsies obtained from patients with psoriasis, will be studied to evaluate JAK/STAT pathway by using immunohistochemical methods	Diagnostic Test: 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.
Healthy Subjects Skin biopsies obtained from patients with healthy subjects, will be used to control group.	Diagnostic Test: 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.

Outcome Measures

Primary Outcome Measures

Expression of JAK-STAT pathway [15 years]
Expression of JAK1, JAK2, JAK3, Tyrosine Kinase 2, STAT1, STAT2, STAT3, STAT3, STAT4, STAT5 and STAT6 in tissue levels in PG.