Autoimmune Diseases, Bullous Dermatoses, Pemphigus Vulgaris
Conditions
Keywords
pemphigus, Th17, IL-23, IL-17, autoimmune bullous disease
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.
Interventions
None listed
Sponsors
Hospital General Dr. Manuel Gea González
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Study design
Observational model
CASE_CONTROL
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Level of Th17 cytokines in skin of pemphigus vulgaris subjects | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Disease activity | 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. |
| Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) | 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 |
| Treatment | Enrollment | The medications and doses used since the diagnosis and during the study |
| Proportion of Th17 and Treg populations on skin biopsies | 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. |
| Level of Th17 cytokines in serum of pemphigus vulgaris subjects | Enrollment | The level of IL-17a, IL-21, IL-22 and IL-23 determined by luminometry |
| Level of Th17 chemokines levels | Enrollment | The level of CCL20 and CXCL8 mRNA from skin biopsies and in serum by luminometry |
| Pemphigus Disease Area Index (PDAI) | 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 |
| Level of Treg chemokines | Enrollment | Determinations at the moment of enrollment and at the termination visit in skin (RT-PCR) and serum (luminometry) |
| P-glycoprotein transporter activity in mononuclear peripheral cells | Enrollment | The activity will be a measure of the percentage of efflux of daunorubicin ar 37°C. |
| Percentage of Th17 peripheral cells with expression of P-glycoprotein on the surface | Enrollment | Cells with the phenotype IL-17a+CCR6+CXR3hiCCR4loCCR10-CD161+PGP+ will be measured with flow cytometry |
| Levels of anti-desmogleins 1 and 3 | Enrollment | Levels will be measures with an ELISA assay |
| Proportion of peripheral cellular subpopulations | Enrollment | Determinations with flow cytometry |
| Level of cytokines in supernatant of cellular culture | Enrollment | Determinations at the moment of enrollment with ELISA |
| Level of Treg cytokines | Enrollment | Determination in skin (RT-PCR) and serum (luminometry) of CCL20 and CXCL8 |
Countries
Mexico
Contacts
Primary ContactLuis Guillermo Llorente Peters, MD
Backup ContactAlba Cicero Casarrubias, MD
Outcome results
None listed