Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The primary objective of this study is to describe and compare plasmatic anti-proteasome auto-antibody concentrations among three distinct groups: (1) patients suffering from bullous pemphigoide; (2) patients suffering from other dermatological auto-immune diseases; (3) an elderly control group.

Condition or disease
Pemphigoid, Bullous; Pemphigus; Lupus Erythematosus, Cutaneous

Detailed Description:

The secondary objectives of this study are:

To compare the following parameters between the 3 groups:

• plasmatic proteasome concentrations
• plasmatic proteasome proteolytic activity

To explore the potential relationships between:

• plasmatic proteasome concentrations
• plasmatic proteasome proteolytic activity
• plasmatic anti-proteasome auto-antibody concentrations
• measures of disease severity for dermatological auto-immune diseases

To characterize plasmatic anti-proteasome auto-antibodies in patients suffering from bullous pemphigoide and other dermatological auto-immune diseases (other bullous auto immune diseases: pemphigus, cutaneous lupus, ...).

To characterize the expression and the activity of proteasomes in skin samples, in plasma and in circulating mononuclear cells in patients with bullous pemphigoide.

Study Design

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Study Type :	Observational
Estimated Enrollment :	130 participants
Observational Model:	Cohort
Time Perspective:	Cross-Sectional
Official Title:	Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid
Study Start Date :	November 2013
Estimated Primary Completion Date :	November 2016
Estimated Study Completion Date :	November 2016

Groups and Cohorts

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Group/Cohort
Bullous pemphigoid; Patients in this cohort are newly diagnosed (or have not started treatment) with bullous pemphigoid
Other bullous-like auto-immune; Patients in this cohort are newly diagnosed (or have not started treatment) with pemphigus (15 patients) or cutaneous lupus (15 patients)
Control group; Patients in this cohort are hospitalized at the Nîmes University Hospital, and have no history of autoimmune, inflammatory or neoplastic disease. Patients are matched for age and sex with patients in the bullous pemphigoid cohort.

Outcome Measures

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Primary Outcome Measures :

1. Plasmatic concentration of anti-proteasome autoantibodies (ng/ml) [ Time Frame: baseline ]

Secondary Outcome Measures :

1. the daily number of new lesions [ Time Frame: baseline ]
   For patients suffering from bullous pemphigoid or pemphigus: the daily number of new lesions for the 3 days preceding blood sampling
2. Presence/absence of mucosal disease [ Time Frame: baseline ]
   For patients suffering from bullous pemphigoid only
3. Disease duration (weeks) [ Time Frame: baseline ]
   For patients suffering from bullous pemphigoid or pemphigus or lupus
4. % surface area [ Time Frame: baseline ]
   For patients suffering from bullous pemphigoid or pemphigus or lupus: % of skin area affected in relation to total area
5. Puritis score [ Time Frame: baseline ]
   For patients suffering from bullous pemphigoid only: severity of itching on a analog scale varying from 0 to 6
6. concentration of anti-PB18 antibodies, measured by ELISA [ Time Frame: baseline ]
   For patients suffering from bullous pemphigoid only; U/ml
7. Immunohistochemistry [ Time Frame: baseline ]
   For the first 10 patients suffering from bullous pemphigoid included at the Nîmes University Hospital only; Skin biopsy immunohistochemistry scores for the pan-alpha, alpha6, beta1, beta2, beta1i, beta5i and rpt5 subunits (negative, weak, moderate, strong)
8. Tissue DNA expression [ Time Frame: baseline ]
   For the first 10 patients suffering from bullous pemphigoid included at the Nîmes University Hospital only; Skin biopsy, plasma and circulating mononuclear cell DNA expression for the pan-alpha, alpha6, beta1, beta2, beta1i, beta5i and rpt5 subunits (weighted by beta-actin)
9. presence/absence of oral lesions [ Time Frame: baseline ]
   For patients suffering from pemphigus
10. Presence/absence of Nikolsky's sign [ Time Frame: baseline ]
    For patients with pemphigus only
11. Pemphigus disease area index [ Time Frame: baseline ]
    For patients with Pemphigus only; score varying from 0 to 120.
12. Anti-desmogleine 1 and 3 antibody concentrations [ Time Frame: baseline ]
    For patients with Pemphigus only; ELISA (U/ml
13. CLASI score for lupus [ Time Frame: baseline ]
    for lupus patients only; score varying from 0 to 70
14. Karnofsky's score (%) [ Time Frame: baseline ]
15. Plasma proteasome concentration [ Time Frame: baseline ]
    ng/ml
16. % trypsin-like plasma proteasome proteolytic activity [ Time Frame: baseline ]
17. % chymotrypsin-like plasma proteasome proteolytic activity [ Time Frame: baseline ]
18. % caspase-like plasma proteasome proteolytic activity [ Time Frame: baseline ]

Biospecimen Retention:   Samples With DNA

All left over plasma samples will be incorporated into the biological collection at the Nîmes University Hospital.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes
Sampling Method:	Non-Probability Sample

Study Population

The study population is composed of three groups: (1) 50 patients with newly diagnosed (untreated) bullous pemphigoid, (2) 50 control patients matched for age and sex with the previous group and (3) 30 patients with other dermatological auto-immune disease (15 pemphigus + 15 cutaneous lupus).

Criteria

Inclusion Criteria:

• The patient must have given his/her informed and signed consent
• The patient must be insured or beneficiary of a health insurance plan
• The patient is not taking systemic treatment
• The patient has not been treated with topical steroids for more than 15 days.

For the bullous pemphigoid group:

• clinical signs: erythematous-based lesions, especially on flexion areas of the arms and legs, not afflicting mucous membranes, and without atrophic scaring
• histology: without epidermal acantholysis

For the pemphigus group:

• patient with pemphigus

For the lupus group:

• systemic lupus patients: presence of the 4 diagnostic criteria for systemic lupus erythematosus as defined by the American College of Rheumatology (amended 1997)
• or characteristics of subacute cutaneous lupus: clinical, histological and immunological (anti-SSa)
• or clinical and histological characteristics of chronic lupus

For the control group:

• hospitalized patients with no history of auto-immune, inflammatory or evolving neoplastic disease

Exclusion Criteria:

• The patient is participating in another study
• The patient is in an exclusion period determined by a previous study
• The patient is under judicial protection, under tutorship or curatorship
• The patient refuses to sign the consent
• It is impossible to correctly inform the patient
• The patient is pregnant, parturient, or breastfeeding

For patients with bullous pemphigoid, pemphigus or lupus:

• The patient is taking systemic treatment
• The patient has been taking topical steroids for more than 15 days.

For the controls:

• autoimmune disease
• inflammatory disease
• evolving neoplastic disease
• surgery during the last 6 months

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Contacts

Contact: Pierre Stoebner, MD	+33.(0)4.66.68.40.43	pierre.stoebner@chu-nimes.fr
Contact: Carey M Suehs, Ph D	+33.(0)4.66.68.67.88	carey.suehs@chu-nimes.fr

Locations

France
CHU de Nîmes - Hôpital Universitaire Carémeau	Recruiting
Nîmes Cedex 09, France, 30029
Principal Investigator: Pierre Stoebner, MD
Sub-Investigator: Laurent Meunier, MD PhD
Sub-Investigator: Lavabre-Bertrand Thierry, MD PhD
Sub-Investigator: Pascal Roger, MD PhD
Sub-Investigator: Jacques Ripart, MD PhD
Sub-Investigator: Gérard Ascencio, MD PhD
Sub-Investigator: Gérard Dupeyron, MD

Sponsors and Collaborators

Centre Hospitalier Universitaire de Nīmes

Investigators

Principal Investigator:	Pierre Stoebner, MD	Centre Hospitalier Universitaire de Nîmes

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:	NCT01559155 History of Changes
Other Study ID Numbers:	LOCAL/2011/PS-02; 2012-A00180-43 ( Other Identifier: RCB number )
First Posted:	March 21, 2012
Last Update Posted:	March 31, 2016
Last Verified:	March 2016

Keywords provided by Centre Hospitalier Universitaire de Nīmes:

proteasomes; proteasome concentration; disease activity	proteolytic activity; autoantibodies; proteasome autoantibody

Additional relevant MeSH terms:

Autoimmune Diseases; Pemphigus; Pemphigoid, Bullous; Lupus Erythematosus, Cutaneous; Immune System Diseases; Skin Diseases, Vesiculobullous	Skin Diseases; Connective Tissue Diseases; Autoantibodies; Dermatologic Agents; Immunologic Factors; Physiological Effects of Drugs