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

Autoimmune Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04096222
• Other study ID #: 3012
• Status: Recruiting
• Start date: June 29, 2021
• Est. completion date: March 28, 2023

Study information

• Verified date: March 2022
• Source: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
• Contact: Luis Guillermo Llorente Peters, MD
• Phone: 525554870900
• Email: luisllorentepeters57[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 42
• Est. completion date: March 28, 2023
• Est. primary completion date: March 28, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Bullous Dermatoses
• Pemphigus
• Pemphigus Vulgaris
• Skin Diseases

Locations

Country	Name	City	State
Mexico	Hospital General Dr. Manuel Gea González	Mexico City
Mexico	Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Mexico City

Sponsors (2)

Lead Sponsor	Collaborator
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran	Hospital General Dr. Manuel Gea González

Country where clinical trial is conducted

Mexico, 

References & Publications (70)

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* Note: There are 70 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pemphigus Disease Area Index (PDAI)	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
Other	Disease activity	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
Other	Autoimmune Bullous Skin Disorder Intensity Score (ABSIS)	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
Other	Treatment	The medications and doses used since the diagnosis and during the study	Enrollment
Other	Proportion of Th17 and Treg populations on skin biopsies	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
Other	Level of Th17 cytokines in serum of pemphigus vulgaris subjects	The level of IL-17a, IL-21, IL-22 and IL-23 determined by luminometry	Enrollment
Other	Level of Th17 chemokines levels	The level of CCL20 and CXCL8 mRNA from skin biopsies and in serum by luminometry	Enrollment
Other	Level of Treg cytokines	Determination in skin (RT-PCR) and serum (luminometry) of CCL20 and CXCL8	Enrollment
Other	Level of Treg chemokines	Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry)	Enrollment
Other	P-glycoprotein transporter activity in mononuclear peripheral cells	The activity will be a measure of the percentage of efflux of daunorubicin ar 37°C.	Enrollment
Other	Percentage of Th17 peripheral cells with expression of P-glycoprotein on the surface	Cells with the phenotype IL-17a+CCR6+CXR3hiCCR4loCCR10-CD161+PGP+ will be measured with flow cytometry	Enrollment
Other	Levels of anti-desmogleins 1 and 3	Levels will be measures with an ELISA assay	Enrollment
Other	Proportion of peripheral cellular subpopulations	Determinations with flow cytometry	Enrollment
Other	Level of cytokines in supernatant of cellular culture	Determinations at the moment of enrollment with ELISA	Enrollment
Primary	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