Clinical trial NCT04096222: Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients
Official title: Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pemphigus Vulgaris
Bullous Dermatoses
Autoimmune Diseases
Keywords: pemphigus
Th17
IL-23
IL-17
autoimmune bullous disease
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: Hospital General Dr. Manuel Gea González
First posted: 2019-09-19
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: OTHER
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.

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Level of Th17 cytokines in skin of pemphigus vulgaris subjects
timeFrame: Enrollment
Secondary outcomes:
Other outcomes:
measure: Pemphigus Disease Area Index (PDAI)
timeFrame: Enrollment
measure: Disease activity
timeFrame: Enrollment
measure: Autoimmune Bullous Skin Disorder Intensity Score (ABSIS)
timeFrame: Enrollment
measure: Treatment
timeFrame: Enrollment
measure: Proportion of Th17 and Treg populations on skin biopsies
timeFrame: Enrollment
measure: Level of Th17 cytokines in serum of pemphigus vulgaris subjects
timeFrame: Enrollment
measure: Level of Th17 chemokines levels
timeFrame: Enrollment
measure: Level of Treg cytokines
timeFrame: Enrollment
measure: Level of Treg chemokines
timeFrame: Enrollment
measure: P-glycoprotein transporter activity in mononuclear peripheral cells
timeFrame: Enrollment
measure: Percentage of Th17 peripheral cells with expression of P-glycoprotein on the surface
timeFrame: Enrollment
measure: Levels of anti-desmogleins 1 and 3
timeFrame: Enrollment
measure: Proportion of peripheral cellular subpopulations
timeFrame: Enrollment
measure: Level of cytokines in supernatant of cellular culture
timeFrame: Enrollment
Locations:
city: Mexico City
country: Mexico
facility: Hospital General Dr. Manuel Gea González
city: Mexico City
country: Mexico
facility: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study officials:
affiliation: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
name: Luis Guillermo Llorente Peters, MD
role: PRINCIPAL_INVESTIGATOR
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