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

August 8, 2022 updated by: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Anticipated)

42

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Mexico
      • Mexico City, Mexico, 14080
        • Recruiting
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
        • Contact:
        • Contact:
      • Mexico City, Mexico, 14080
        • Not yet recruiting
        • Hospital General Dr. Manuel Gea González

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects with the diagnosis of pemphigus who are 18 or older and who have curent skin activity and will receive treatment with corticosteroids with or without adjuvants. At the moment of enrollment subjects shoould not be pregnant, have concurrent autoimmune diseases with skin lesions (eg cutaneous lupus), cancer or infectious diseases.

Description

Inclusion Criteria:

  1. Current cutaneous activity of pemphigus
  2. Subjects will be treated with corticosteroids with or without adjuvants
  3. Accept and sign the informed consent

Exclusion Criteria:

  1. Pregnancy
  2. Concurrent autoimmune diseases with skin lesions
  3. Concurrent diagnosis of cancer
  4. Concurrent active infectious disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Active pemphigus vulgaris subjects
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
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
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?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Level of Th17 cytokines in skin of pemphigus vulgaris subjects
Time Frame: Enrollment
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

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pemphigus Disease Area Index (PDAI)
Time Frame: Enrollment
PDAI has a total of 0-263 points, 250 are related to activity and 13 to damage. Disease severity is considered as follows: 1) moderate <= 14 points; b) significative 15-44 points; and c) extensive >=45
Enrollment
Disease activity
Time Frame: Enrollment
Measured with Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS). PDAI has a total of 0-263 points, 250 are related to activity and 13 to damage. ABSIS has a total score of 0-206.
Enrollment
Autoimmune Bullous Skin Disorder Intensity Score (ABSIS)
Time Frame: Enrollment
ABSIS has a total score of 0-206. Disease severity is considered as follows: 1) moderate <= 16 points; b) significative 17-52 points; and c) extensive >=53
Enrollment
Treatment
Time Frame: Enrollment
The medications and doses used since the diagnosis and during the study
Enrollment
Proportion of Th17 and Treg populations on skin biopsies
Time Frame: Enrollment
iopsies will be processed for immunohistochemistry for TH17 subsets (CD+IL17a+) and Treg subset (CD25+Foxp3+). The proportion of both subsets will be quantified with specialized software.
Enrollment
Level of Th17 cytokines in serum of pemphigus vulgaris subjects
Time Frame: Enrollment
The level of IL-17a, IL-21, IL-22 and IL-23 determined by luminometry
Enrollment
Level of Th17 chemokines levels
Time Frame: Enrollment
The level of CCL20 and CXCL8 mRNA from skin biopsies and in serum by luminometry
Enrollment
Level of Treg cytokines
Time Frame: Enrollment
Determination in skin (RT-PCR) and serum (luminometry) of CCL20 and CXCL8
Enrollment
Level of Treg chemokines
Time Frame: Enrollment
Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry)
Enrollment
P-glycoprotein transporter activity in mononuclear peripheral cells
Time Frame: Enrollment
The activity will be a measure of the percentage of efflux of daunorubicin ar 37°C.
Enrollment
Percentage of Th17 peripheral cells with expression of P-glycoprotein on the surface
Time Frame: Enrollment
Cells with the phenotype IL-17a+CCR6+CXR3hiCCR4loCCR10-CD161+PGP+ will be measured with flow cytometry
Enrollment
Levels of anti-desmogleins 1 and 3
Time Frame: Enrollment
Levels will be measures with an ELISA assay
Enrollment
Proportion of peripheral cellular subpopulations
Time Frame: Enrollment
Determinations with flow cytometry
Enrollment
Level of cytokines in supernatant of cellular culture
Time Frame: Enrollment
Determinations at the moment of enrollment with ELISA
Enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Collaborators

Hospital General Dr. Manuel Gea González

Investigators

  • Principal Investigator: Luis Guillermo Llorente Peters, MD, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 29, 2021

Primary Completion (ANTICIPATED)

March 28, 2023

Study Completion (ANTICIPATED)

March 28, 2023

Study Registration Dates

First Submitted

August 15, 2019

First Submitted That Met QC Criteria

September 18, 2019

First Posted (ACTUAL)

September 19, 2019

Study Record Updates

Last Update Posted (ACTUAL)

August 10, 2022

Last Update Submitted That Met QC Criteria

August 8, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 3012

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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