Pemphigus VulgarisNCT03177213
Serum IL-21 Levels in Patients With Pemphigus Vulgaris
An observational study of Pemphigus Vulgaris, run by Assiut University.
Trial summary
Pemphigus is severe antigen derived autoimmune bullous skin disorder, the word pemphigus is derived from the Greek word" pemphix " which means blister . Two main clinical variants are known pemphigus vulgaris (PV), and pemphigu foliaceus (PF). (Zenzo .et al., 2015). Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Pemphigus Vulgaris
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Jun 2017to Dec 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: 20 pemphigus vulgaris patients will be included in the study, either newly diagnosed or recurrent. Patients will be recruited on admission from Dermatology department and Outpatient Clinic, Assiut University Hospitals. 10 healthy age and sex matched subjects will be included as controls.
Who may be able to join
- 20 pemphigus vulgaris patients
- healthy age and sex matched
Who cannot join
- - Patients with a history of topical or systemic treatment (corticosteroids, intralesional steroid injection, immunosuppressive therapy, anticonvulsants and anticancer medications, within 4 weeks of the study.
- Patients receiving phototherapy within 6 months of the study .
- Patients with a history of diabetes mellitus, anemia, thyroid or parathyroid disorders, chronic liver or renal diseases, or atopy .
- Patients with known autoimmune diseases or cancer.
- Pregnant or lactating women were also excluded from the study.
Trial locations and contacts
No sites are listed yet.
About this study
Pemphigus is severe antigen derived autoimmune bullous skin disorder, the word pemphigus is derived from the Greek word" pemphix " which means blister . Two main clinical variants are known pemphigus vulgaris (PV), and pemphigu foliaceus (PF). (Zenzo .et al., 2015).
Read the detailed description
Clinically, there are localized or generalized flaccid bullae that quickly transform into post-bullous erosions and crusts , PV patients characteristically develop oral lesions with buccal and/or gingival persisting erosions (mucosal dominant PV) which several weeks or months later may also spread to the epidermis (mucocutaneous PV). PF is characterized by widespread cutaneous fragile bullae which rapidly rupture, resulting in erosions, crusting, and scaling. In contrast to PV, the mucosa is usually not involved in PV. (Zenzo .et al .,2015).
Pathophysiologically, the underlying intraepithelial blister formation is caused by IgG autoantibodies against the desmosomal adhesion proteins, desmoglein 3 and/or desmoglein 1, on epidermal keratinocytes. ( Amagai .et al .,1991) In PV the antigen is desmoglein 3 which is presented in lower epidermis and is expressed more strongly in buccal mucosa than in the skin ,in contrast to PF which its antigen is desmoglein 1 which is expressed in the skin throughout the epidermis and weakly expressed in the mucous membranes . ( Kneisel and Hertl. .,2011).
T cells play a crucial role in the pathogenesis of pemphigus vulgaris , The interaction of T and B cells critically modulates the development of pemphigus vulgaris. (Amber. et al., 2013 ; Zhu, et al.,2012).
Because B-cell activation and antibody production classically necessitate the involvement of CD4+ T cells, Dsg-reactive T cells were capable of recognizing multiple epitopes of the extracellular domain of Dsg and helping B cells to produce a specific antibody. Dsg3-reactive T-cell clones were able to commit polyclonal naive B cells to produce pathogenic anti-Dsg3 antibody and induce the PV phenotype. (Hertl . et al., 1998) Follicular T helper cells (Tfh) are a recently discovered group of CD4+ Th cells with intrinsic differences from Th1, Th2 and Th17 cells. Localized in B-cell follicles of secondary lymphoid tissues, The major function of Tfh cells appears to help B-cell activation and antibody production during humoral immune responses. The Tfh cells express high levels of IL-21, which was demonstrated to be important for the generation of Tfh cells and that responsiveness of Tfh cells to IL-21 drives the formation of the autoimmune reaction, and it clearly impacted on the amount of antibody production.( Gomez. et al.,2011 ; Vogelzang . et al.,2008) Nowadays, finding a promising treatment for pemphigus remains a serious challenge. Various treatments are currently recommended to treat this disease, but they rarely lead to complete and durable remission. Regulatory cells appear to have a critical role in numerous autoimmune diseases, so it is possible that control of these cells may induce remission. (Cholera and Chainani .,2016)
- Conditions
- Pemphigus Vulgaris
- Medical subject headings
- Pemphigus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| pemphigus vulgaris patients | 20 pemphigus vulgaris patients will be included in the study, either newly diagnosed or recurrent. Patients will be recruited on admission from Dermatology department and Outpatient Clinic, Assiut University Hospitals | |
| Healthy controls | 10 healthy age and sex matched subjects will be included as controls. |
What is being measured
The primary outcome is the main question the study is designed to answer.
serum IL-21
serum IL-21 level
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2017
- Study startJun 2017 (estimated)
- Primary completionSep 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Pemphigus VulgarisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marwa Kassim, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03177213
- Sponsor's protocol ID
- IL-21PV
- Status last verified
- Jun 2017
- First submitted
- 2 Jun 2017
- Last updated
- 6 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zhu H, Chen Y, Zhou Y, Wang Y, Zheng J, Pan M. Cognate Th2-B cell interaction is essential for the autoantibody production in pemphigus vulgaris. J Clin Immunol. 2012 Feb;32(1):114-23. doi: 10.1007/s10875-011-9597-4. Epub 2011 Oct 19.
PubMed 22009001Amber KT, Staropoli P, Shiman MI, Elgart GW, Hertl M. Autoreactive T cells in the immune pathogenesis of pemphigus vulgaris. Exp Dermatol. 2013 Nov;22(11):699-704. doi: 10.1111/exd.12229.
PubMed 24433179Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991 Nov 29;67(5):869-77. doi: 10.1016/0092-8674(91)90360-b.
PubMed 1720352Cholera M, Chainani-Wu N. Management of Pemphigus Vulgaris. Adv Ther. 2016 Jun;33(6):910-58. doi: 10.1007/s12325-016-0343-4. Epub 2016 Jun 10.
PubMed 27287854Di Zenzo G, Amber KT, Sayar BS, Muller EJ, Borradori L. Immune response in pemphigus and beyond: progresses and emerging concepts. Semin Immunopathol. 2016 Jan;38(1):57-74. doi: 10.1007/s00281-015-0541-1. Epub 2015 Nov 23.
PubMed 26597100Gomez-Martin D, Diaz-Zamudio M, Romo-Tena J, Ibarra-Sanchez MJ, Alcocer-Varela J. Follicular helper T cells poise immune responses to the development of autoimmune pathology. Autoimmun Rev. 2011 Apr;10(6):325-30. doi: 10.1016/j.autrev.2010.11.007. Epub 2010 Dec 15.
PubMed 21167320Hertl M, Amagai M, Sundaram H, Stanley J, Ishii K, Katz SI. Recognition of desmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals. J Invest Dermatol. 1998 Jan;110(1):62-6. doi: 10.1046/j.1523-1747.1998.00086.x.
PubMed 9424089Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: Clinical manifestations. J Dtsch Dermatol Ges. 2011 Oct;9(10):844-56; quiz 857. doi: 10.1111/j.1610-0387.2011.07793.x. English, German.
PubMed 21955378Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 2: diagnosis and therapy. J Dtsch Dermatol Ges. 2011 Nov;9(11):927-47. doi: 10.1111/j.1610-0387.2011.07809.x. English, German.
PubMed 22026362Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, Fakharzadeh S, Hall R, Korman NJ, Lin J, Okawa J, Pandya AG, Payne AS, Rose M, Rubenstein D, Woodley D, Vittorio C, Werth BB, Williams EA, Taylor L, Troxel AB, Werth VP. Reliability and convergent validity of two outcome instruments for pemphigus. J Invest Dermatol. 2009 Oct;129(10):2404-10. doi: 10.1038/jid.2009.72. Epub 2009 Apr 9.
PubMed 19357707Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C. A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity. 2008 Jul 18;29(1):127-37. doi: 10.1016/j.immuni.2008.06.001. Epub 2008 Jul 3.
PubMed 18602282
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum IL-21 Levels in Patients With Pemphigus Vulgaris
- ClinicalTrials.gov ID
- NCT03177213
- Acronym / sponsor ID
- IL-21PV
- Conditions
- Pemphigus Vulgaris
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- Jun 2017 (estimated)
- Primary completion
- Sep 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 6 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Pemphigus is severe antigen derived autoimmune bullous skin disorder, the word pemphigus is derived from the Greek word" pemphix " which means blister . Two main clinical variants are known pemphigus vulgaris (PV), and pemphigu foliaceus (PF). (Zenzo .et al., 2015).
Detailed description
Clinically, there are localized or generalized flaccid bullae that quickly transform into post-bullous erosions and crusts , PV patients characteristically develop oral lesions with buccal and/or gingival persisting erosions (mucosal dominant PV) which several weeks or months later may also spread to the epidermis (mucocutaneous PV). PF is characterized by widespread cutaneous fragile bullae which rapidly rupture, resulting in erosions, crusting, and scaling. In contrast to PV, the mucosa is usually not involved in PV. (Zenzo .et al .,2015).
Pathophysiologically, the underlying intraepithelial blister formation is caused by IgG autoantibodies against the desmosomal adhesion proteins, desmoglein 3 and/or desmoglein 1, on epidermal keratinocytes. ( Amagai .et al .,1991) In PV the antigen is desmoglein 3 which is presented in lower epidermis and is expressed more strongly in buccal mucosa than in the skin ,in contrast to PF which its antigen is desmoglein 1 which is expressed in the skin throughout the epidermis and weakly expressed in the mucous membranes . ( Kneisel and Hertl. .,2011).
T cells play a crucial role in the pathogenesis of pemphigus vulgaris , The interaction of T and B cells critically modulates the development of pemphigus vulgaris. (Amber. et al., 2013 ; Zhu, et al.,2012).
Because B-cell activation and antibody production classically necessitate the involvement of CD4+ T cells, Dsg-reactive T cells were capable of recognizing multiple epitopes of the extracellular domain of Dsg and helping B cells to produce a specific antibody. Dsg3-reactive T-cell clones were able to commit polyclonal naive B cells to produce pathogenic anti-Dsg3 antibody and induce the PV phenotype. (Hertl . et al., 1998) Follicular T helper cells (Tfh) are a recently discovered group of CD4+ Th cells with intrinsic differences from Th1, Th2 and Th17 cells. Localized in B-cell follicles of secondary lymphoid tissues, The major function of Tfh cells appears to help B-cell activation and antibody production during humoral immune responses. The Tfh cells express high levels of IL-21, which was demonstrated to be important for the generation of Tfh cells and that responsiveness of Tfh cells to IL-21 drives the formation of the autoimmune reaction, and it clearly impacted on the amount of antibody production.( Gomez. et al.,2011 ; Vogelzang . et al.,2008) Nowadays, finding a promising treatment for pemphigus remains a serious challenge. Various treatments are currently recommended to treat this disease, but they rarely lead to complete and durable remission. Regulatory cells appear to have a critical role in numerous autoimmune diseases, so it is possible that control of these cells may induce remission. (Cholera and Chainani .,2016)
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| pemphigus vulgaris patients | – | –20 pemphigus vulgaris patients will be included in the study, either newly diagnosed or recurrent. Patients will be recruited on admission from Dermatology department and Outpatient Clinic, Assiut University Hospitals |
| Healthy controls | – | –10 healthy age and sex matched subjects will be included as controls. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- 20 pemphigus vulgaris patients will be included in the study, either newly diagnosed or recurrent. Patients will be recruited on admission from Dermatology department and Outpatient Clinic, Assiut University Hospitals. 10 healthy age and sex matched subjects will be included as controls.
Key inclusion criteria (2 listed)
- 20 pemphigus vulgaris patients
- healthy age and sex matched
Key exclusion criteria (5 listed)
- - Patients with a history of topical or systemic treatment (corticosteroids, intralesional steroid injection, immunosuppressive therapy, anticonvulsants and anticancer medications, within 4 weeks of the study.
- Patients receiving phototherapy within 6 months of the study .
- Patients with a history of diabetes mellitus, anemia, thyroid or parathyroid disorders, chronic liver or renal diseases, or atopy .
- Patients with known autoimmune diseases or cancer.
- Pregnant or lactating women were also excluded from the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
serum IL-21
Time frame: 2 months
serum IL-21 level
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2017.
- Background: PubMed 22009001Zhu H, Chen Y, Zhou Y, Wang Y, Zheng J, Pan M. Cognate Th2-B cell interaction is essential for the autoantibody production in pemphigus vulgaris. J Clin Immunol. 2012 Feb;32(1):114-23. doi: 10.1007/s10875-011-9597-4. Epub 2011 Oct 19.
- Results publication: PubMed 24433179Amber KT, Staropoli P, Shiman MI, Elgart GW, Hertl M. Autoreactive T cells in the immune pathogenesis of pemphigus vulgaris. Exp Dermatol. 2013 Nov;22(11):699-704. doi: 10.1111/exd.12229.
- Results publication: PubMed 1720352Amagai M, Klaus-Kovtun V, Stanley JR. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion. Cell. 1991 Nov 29;67(5):869-77. doi: 10.1016/0092-8674(91)90360-b.
- Results publication: PubMed 27287854Cholera M, Chainani-Wu N. Management of Pemphigus Vulgaris. Adv Ther. 2016 Jun;33(6):910-58. doi: 10.1007/s12325-016-0343-4. Epub 2016 Jun 10.
- Results publication: PubMed 26597100Di Zenzo G, Amber KT, Sayar BS, Muller EJ, Borradori L. Immune response in pemphigus and beyond: progresses and emerging concepts. Semin Immunopathol. 2016 Jan;38(1):57-74. doi: 10.1007/s00281-015-0541-1. Epub 2015 Nov 23.
- Results publication: PubMed 21167320Gomez-Martin D, Diaz-Zamudio M, Romo-Tena J, Ibarra-Sanchez MJ, Alcocer-Varela J. Follicular helper T cells poise immune responses to the development of autoimmune pathology. Autoimmun Rev. 2011 Apr;10(6):325-30. doi: 10.1016/j.autrev.2010.11.007. Epub 2010 Dec 15.
- Results publication: PubMed 9424089Hertl M, Amagai M, Sundaram H, Stanley J, Ishii K, Katz SI. Recognition of desmoglein 3 by autoreactive T cells in pemphigus vulgaris patients and normals. J Invest Dermatol. 1998 Jan;110(1):62-6. doi: 10.1046/j.1523-1747.1998.00086.x.
- Results publication: PubMed 21955378Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 1: Clinical manifestations. J Dtsch Dermatol Ges. 2011 Oct;9(10):844-56; quiz 857. doi: 10.1111/j.1610-0387.2011.07793.x. English, German.
- Results publication: PubMed 22026362Kneisel A, Hertl M. Autoimmune bullous skin diseases. Part 2: diagnosis and therapy. J Dtsch Dermatol Ges. 2011 Nov;9(11):927-47. doi: 10.1111/j.1610-0387.2011.07809.x. English, German.
- Results publication: PubMed 19357707Rosenbach M, Murrell DF, Bystryn JC, Dulay S, Dick S, Fakharzadeh S, Hall R, Korman NJ, Lin J, Okawa J, Pandya AG, Payne AS, Rose M, Rubenstein D, Woodley D, Vittorio C, Werth BB, Williams EA, Taylor L, Troxel AB, Werth VP. Reliability and convergent validity of two outcome instruments for pemphigus. J Invest Dermatol. 2009 Oct;129(10):2404-10. doi: 10.1038/jid.2009.72. Epub 2009 Apr 9.
- Results publication: PubMed 18602282Vogelzang A, McGuire HM, Yu D, Sprent J, Mackay CR, King C. A fundamental role for interleukin-21 in the generation of T follicular helper cells. Immunity. 2008 Jul 18;29(1):127-37. doi: 10.1016/j.immuni.2008.06.001. Epub 2008 Jul 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
An observational study of Pemphigus Vulgaris, run by Assiut University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hatem Zi Mohammed, Professor (01003420217, zedanhzma@aun.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
serum IL-21 (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03177213, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2017.