Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients

Study Overview
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Brief Summary
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This study will compare the pattern of Th17 immune response in active and inactive pemphigus subjects. Skin and serum samples will be taken at the moment of enrollment.

Detailed Description
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Pemphigus is an autoimmune disease characterized by production of autoantibodies against desmogleins 1 and 3, which are part of the epidermis desmosomes. The first line of treatment are corticosteroids with or without the use of adjuvants (e.g. azathioprine, mycophenolate or rituximab). T lymphocytes are responsible for the initiation and maturation of the humoral response and the B cell activation required for the production of autoantibodies. In the last decade, the Th17 immune response has been implicated in the pathogenesis of pemphigus. Recently, the existence of tertiary lymphoid organ-like structures within the skin lesions was suggested. This structures contain T lymphocytes, B lymphocytes and plasma cells; these cells interact and create a local microenvironment for the production of autoantibodies. Most of the T cells in this structures are T helper CD4+ and express IL-21, and half of them produce IL-17. In this study the investigators aim to evaluate comparatively the Th17 and T regulatory immune response in the lesional skin and serum of active and inactive pemphigus subjects that are treated with corticosteroids with or without adjuvants and a third group of healthy subjects. The investigators will study skin and serum due to the difference of lymphocytes and cytokines in both tissues. The primary hypothesis is: active pemphigus vulgaris subjects will have different levels of TH17 response in comparison to inactive patients. The investigators will use descriptive statistics, association and correlation test of hypothesis.

Official Title
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Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients

Conditions
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Pemphigus Vulgaris, Bullous Dermatoses, Autoimmune Diseases

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current cutaneous activity of pemphigus Subjects will be treated with corticosteroids with or without adjuvants Accept and sign the informed consent Exclusion Criteria: Pregnancy Concurrent autoimmune diseases with skin lesions Concurrent diagnosis of cancer Concurrent active infectious disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active pemphigus vulgaris subjects<br>Subjects with the diagnosis of pemphigus and with active or inactive disease in the skin will be invited to participate. After informed consent, at the enrollment visit the following interventions will be done: 1) two 4 mm punch biopsies in a target lesion, 2) A 34 ml blood sample will be taken, 3) photographs of the subject, 4) demographic, disease, comorbidity and treatment data will be documented, 5) PDAI and ABSIS, 6) Biometric data | |
| Inactive pemphigus vulgaris subjects<br>Subjects with the diagnosis of pemphigus and with active or inactive disease in the skin will be invited to participate. After informed consent, at the enrollment visit the following interventions will be done: 1) two 4 mm punch biopsies in a target lesion, 2) A 34 ml blood sample will be taken, 3) photographs of the subject, 4) demographic, disease, comorbidity and treatment data will be documented, 5) PDAI and ABSIS, 6) Biometric data | |
| Healthy subjects<br>Healthy subjects will be invited to participate. After informed consent, at the enrollment visit the following interventions will be done: 1) Demographic data will be documented, 2) biometric data, 3) A 34 ml blood sample will be taken | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Level of Th17 cytokines in skin of pemphigus vulgaris subjects | The level of IL-17a, IL-21, IL-22, and IL-23 mRNA from skin biopsies at the time of enrollment and when the subject reaches 75% of PDAI improvement or after a year of follow-up (termination visit). The percentage of change in these two determinations will be calculated. | Enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pemphigus, Th17, IL-23, IL-17, autoimmune bullous disease