Gene Expression Of Suppressor Of Cytokines in In Cutaneous Warts

Study Overview
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Brief Summary
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Warts are common epidermal growths caused by various strains of human papilloma virus (HPV). Viral warts are common with a prevalence rate of 7-12%. Human papilloma virus is small non enveloped viruses that contain a double-stranded DNA genome. There are more than 200 HPV genotypes are reported, however, the high-risk types, including HPV genotype-16 (HPV16), 18, 31, and 45, are the causes of 80% of cervical cancers.

Detailed Description
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Cutaneous warts are benign lesions caused by low risk-HPV. Of which the most prevalent genotypes are HPV1/2/3/4/10/27/57, and from these genotypes 1, 2, 4, 27, 57 cause common warts. Palmoplantar warts can be caused by genotypes 1 and 2. Condyloma acuminata (anogenital warts) are common sexually transmitted infections caused primarily by HPV-6 and HPV-11 (in 90% of cases) and occasionally by HPV-16 and HPV-18. About 90% of HPV infections are eliminated within two years due to an efficient immune response. In the form of correct activation of the elements of the innate immune response, such as macrophages, polymorphonuclear cells, natural killer (NK) cells, which release immunomodulatory molecules that help control the infection. In addition, HPV-infected keratinocytes may act as non-professional antigen-presenting cells to promote the clearance of infected cells through the secretion of antiviral and pro-inflammatory mediators. Interferon (IFN) belongs to a family of inducible cytokines which promote anantiviral state in infected cells and neighboring cells through the activation of interferon-stimulated genes (ISG). Three IFN types have been identified (type I, II and III), of which I and III are involved in the innate immune response. Type I IFNs include IFN-α, IFN-β, IFN-ɛ, IFN-κ and IFN-ω. Most type I IFNs are induced through the binding of viral products to pattern recognition receptors, leading to activation of interferon response factors to drive the synthesis of IFN molecules. After secretion, type I IFNs bind to its receptor, which induces the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2, which then translocate to the nucleus to induce transcription of (ISGs). The antiviral effects of IFN-I are mediated by inducing several (ISGs) which impair viral replication through inhibition of protein translation and degradation of viral RNA. ISGs also activate the survival of innate and adaptive immune cells including dendritic cells, macrophages, NK cells and T cells. So, IFN-I helps to control the infections. During the viral infection process, cytokines trigger and deal with inflammation. However, excessive production of cytokines can cause a cytokine storm, and excessive host innate immune response can also damage the body. Therefore, the suppressor of cytokine signaling proteins with negative feedback regulation ability, prevents the excessive secretion of cytokines from harming the host cell. These intracellular protein family is constituted by suppressor of cytokine signaling proteins 1-7, Which are potent endogenous inhibitors of Janus kinase (JAK/ STAT) signal. The SOCS 3 is mainly involved in the negative feedback regulation of the tyrosine-protein kinase/ STAT signaling. The critical role of SOCS3 is manifested by its binding to both the JAK and the tyrosine kinase receptor, which further inhibits STAT3 phosphorylation. The JAK/STAT pathway transduces extracellular signals to the nucleus. Its activation stimulates cell proliferation, differentiation, migration, and immune challenge. The JAK/STAT signaling pathway plays an important role in viral infection. The SOCS family are induced by various viral infections, including human immunodeficiency virus-1, hepatitis B and C viruses, herpes simplex virus type 1, respiratory syncytial virus, Ebola virus, influenza A, and coxsackie virus. Influenza A virus inhibits type I IFN signaling through the induction of SOCS3 expression. Newcastle disease virus (NDV) infection activates the expression of SOCS3 at the mRNA and protein level, which is conducive to the virus replication.

Official Title
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Assessment Of Gene Expression Of Suppressor Of Cytokine 3, Interferons Alpha And Beta In Cutaneous Warts

Conditions
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Warts

Intervention / Treatment
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* Diagnostic Test: Detection of expression of SOCS3 gene
* Diagnostic Test: Detection of expression of IFN-α gene
* Diagnostic Test: Detection of expression of IFN-β gene


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The study will include patients with cutaneous warts of various types aged 18-50 years old. Exclusion Criteria: 1. Pregnancy 2. Lactation 3. Patient on anti-inflammatory and antioxidant drugs 4. Skin infections, other than warts 5. Skin diseases 6. Systemic infection. 7. Malignancies

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| patients with cutaneous warts<br>Under complete sterile precautions, Skin biopsy will be taken from patients with wart lesion. The specimen will be put in sterile plane tube containing saline and will be transferred immediately to the central research laboratory to be processed | Diagnostic Test: Detection of expression of SOCS3 gene<br>* Detection of expression of SOCS3, in each samples using Real-Time PCR<br>Diagnostic Test: Detection of expression of IFN-α gene<br>* Detection of expression of IFN-α gene in each samples using Real-Time PCR<br>Diagnostic Test: Detection of expression of IFN-β gene<br>* Detection of expression of IFN-β gene in each samples using Real-Time PCR<br>|
| healthy volunteers<br>Under complete sterile precautions, Skin biopsy will be taken from healthy volunteers of the control group via 2 mm disposable punches . The specimen will be put in sterile plane tube containing saline and will be transferred immediately to the central research laboratory to be processed | Diagnostic Test: Detection of expression of SOCS3 gene<br>* Detection of expression of SOCS3, in each samples using Real-Time PCR<br>Diagnostic Test: Detection of expression of IFN-α gene<br>* Detection of expression of IFN-α gene in each samples using Real-Time PCR<br>Diagnostic Test: Detection of expression of IFN-β gene<br>* Detection of expression of IFN-β gene in each samples using Real-Time PCR<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This study aims to assess the expression of genes of SOCS3 in cutaneous warts. | Under complete sterile precautions, Skin biopsy will be taken from healthy volunteers of the control group via 2 mm disposable punches and from patients with wart lesion. The specimen will be put in sterile plane tube containing saline and will be transferred immediately to the central research laboratory to be processed as follow: Tissue grinding into smaller pieces then will be subjected for RNA extraction by automated kits according to its manufacture instruction. Conversion of RNA to double stranded DNA using RT( reverse transcriptase conversion Kits ) according to its manufacture instruction using conventional PCR. Detection of expression of SOCS3 gene in each samples using Real-Time PCR | from april 2023 to December 2023 | 
| This study aims to assess the expression of genes of IFN-α in cutaneous warts. | Under complete sterile precautions, Skin biopsy will be taken from healthy volunteers of the control group via 2 mm disposable punches and from patients with wart lesion. The specimen will be put in sterile plane tube containing saline and will be transferred immediately to the central research laboratory to be processed as follow: Tissue grinding into smaller pieces then will be subjected for RNA extraction by automated kits according to its manufacture instruction. Conversion of RNA to double stranded DNA using RT( reverse transcriptase conversion Kits ) according to its manufacture instruction using conventional PCR. Detection of expression of IFN-α gene in each samples using Real-Time PCR | from April 2023 to December 2023 | 
| This study aims to assess the expression of genes of IFN-β in cutaneous warts. | Under complete sterile precautions, Skin biopsy will be taken from healthy volunteers of the control group via 2 mm disposable punches and from patients with wart lesion. The specimen will be put in sterile plane tube containing saline and will be transferred immediately to the central research laboratory to be processed as follow: Tissue grinding into smaller pieces then will be subjected for RNA extraction by automated kits according to its manufacture instruction. Conversion of RNA to double stranded DNA using RT( reverse transcriptase conversion Kits ) according to its manufacture instruction using conventional PCR. Detection of expression of IFN-β gene in each samples using Real-Time PCR | from April 2023 to December 2023 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HPV, Warts, STAT1, SOCS 3