Card14gene (rs34367357 ) Polymorphism in Egyptian Psoriatic and Psoriatic Arthritis Patient
Card14gene (rs34367357 ) Polymorphism in Egyptian Psoriatic and Psoriatic Arthritis Patient and Its Relation With Response to Methotrexate
Psoriasis is a chronic, immune-mediated, multisystemic, inflammatory disease caused by the interaction of multiple susceptibility genes and environmental factors that affects 1-3% of the population worldwide .Psoriasis also is a chronic inflammatory skin disease characterized by scaly indurated erythema.
Psoriatic arthritis (PsA) is an autoimmune and chronic musculoskeletal disorder that is associated with psoriasis of the skin . Its presentation can vary from subtle manifestations to highly destructive forms. Joint pain, stiffness and swelling are the most common symptoms.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
PsA is a complex inflammatory disease with heterogeneous clinical features, which complicates psoriasis in 30% of patients .
The exact aetiopathogenesis of psoriasis is not completely explained. Pathological mechanism involves skin inflammation and hyperproliferation of keratinocytes induced innate and adaptive immune cells. Genetic, immunological and environmental factors are considered the most important aetiologies.
Psoriasis is a chronic relapsing disease, which often necessitates a long-term therapy. Mild to moderate psoriasis can be treated topically with a combination of glucocorticoids, vitamin D analogues, and phototherapy. Moderate to severe psoriasis often requires systemic treatment. The presence of comorbidities such as psoriasis arthritis is also highly relevant in treatment selection.
Methotrexate (MTX) has remained the backbone of the treatment for moderate to severe psoriasis ever since its first use nearly half a century ago.
Over the years, its high efficacy, low cost, relative ease of administration and usefulness in concomitant psoriatic arthritis have contributed in making MTX the drug of choice in managing severe psoriasis. Although the majority of patients achieve remission of disease activity with MTX, a significant proportion may experience mild and transient adverse effects. From time to time, various guidelines on the use of MTX have correctly and adequately stressed the need for strict monitoring of haematological and hepatic adverse events.
The transcription factor known as nuclear factor of kappa light chain enhancer of activated B cells (NF-κB) controls a large number of genes in immune cells in response to inflammation, infection, and other stimuli. Proinflammatory cytokines, chemokines, and growth factors are among the many genes whose transcription is boosted when the NF-κB pathway is activated. These genes are all implicated in the initiation and maintenance of the inflammatory response in psoriatic illness .
The intracellular scaffold protein known as caspase recruitment domain family member 14 (CARD14) rs34367357 is highly abundant in keratinocytes and mediates NF-κB activation by forming a CBM (CARD14-BCL10-MALT1) signaling complex .
Gain-of-function mutations in CARD14 have been demonstrated to increase the development of the CBM complex in keratinocytes, which causes the NF-κB pathway to become hyperactivated. Neutrophils, dendritic cells, and T cells are then drawn in and activated as a result of the transcription of several chemokines (CCL20, CXCL1, and CXCL2), cytokines (IL-36 and IL-19), and antimicrobial peptides. Two key cytokines in the pathophysiology of psoriasis, IL-17 and IL-22, are downstreamly expressed when activated dendritic cells release IL-23 .
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Marwa Naguib Ahmed, MSc
- Phone Number: +201099283315
- Email: omarahmed331166@yahoo.com
Study Contact Backup
- Name: Soheir Abdel-Hamid Ali
- Phone Number: +201066877343
- Email: Soher.abdel-hamed@med.svu.edu.eg
Study Locations
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Qinā, Egypt
- Recruiting
- Qina University hospital, South Valley University Hospital
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Contact:
- Mohamed Hosny Hassan, Professor
- Phone Number: +201098473605
- Email: mohammedhosnyhassaan@med.svu.edu.eg
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Contact:
- Ebtehal Alaa El-Din Kotop Mohamed, Lecturer
- Phone Number: +201066798383
- Email: Ebtehal_alaa@med.svu.edu.eg
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Principal Investigator:
- Shimaa Saber Ahmed., M.D
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients aged 18 years and above.
- Patients having psoriasis diagnosed clinically and who have a severity grade of moderate to severe, defined as a Psoriasis Area and Severity Index (PASI) score from 5- 10 % of body surface area, and involvement of greater than 10% of the body surface area (BSA) with or without psoriatic arthritis
Exclusion Criteria:
- Patients with other autoimmune conditions (e.g., rheumatoid arthritis, systemic lupus erythematosus).
- Pregnancy and lactation.
- Patients currently undergoing immunosuppressive or systemic therapies.
- Patients with known genetic disorders affect immune system function.
- Patients with liver or kidney impairment.
- Patients with allergy or contraindication to methotrexate.
- Patients with active or uncontrolled infections, including chronic infections like tuberculosis.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Active Comparator: Group A
About 20 patients with psoriasis
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Other Names:
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Active Comparator: Group B
About 20 psoriatic arthritis
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Other Names:
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Placebo Comparator: Group C
About 10 healthy control group
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Placebo
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Psoriasis Treatment
Time Frame: 3 Months
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Assessing the Response of psoriasis and psoriatic arthritis to Methotrexate by assessment and complete cutaneous examination to evaluate the clinical type and severity of psoriasis using PASI score
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3 Months
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Collaborators and Investigators
Sponsor
Investigators
- Study Chair: Essam El-Din Abd El-Aziz Mohamed Ahmed Nada, Professor, Dermatology, Venereology and Andrology Sohag university
- Study Director: Eisa Mohammed Hegazy, Professor, • Dermatology Venereology & Andrology Faculty of Medicine, South valley University.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Bone Diseases
- Musculoskeletal Diseases
- Joint Diseases
- Spinal Diseases
- Spondylarthropathies
- Skin Diseases, Papulosquamous
- Skin Diseases
- Spondylarthritis
- Spondylitis
- Psoriasis
- Arthritis
- Arthritis, Psoriatic
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Abortifacient Agents, Nonsteroidal
- Abortifacient Agents
- Reproductive Control Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Dermatologic Agents
- Folic Acid Antagonists
- Nucleic Acid Synthesis Inhibitors
- Methotrexate
Other Study ID Numbers
- Card14gene polymorphism
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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