Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

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.

Study Overview

• Status: Terminated
• Conditions: Pemphigoid, Bullous; Lupus Erythematosus, Cutaneous; Pemphigus

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 Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

Study Locations

• France
  • Nîmes Cedex 09, France, 30029
    • CHU de Nîmes - Hopital Universitaire Caremeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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).

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Plasmatic concentration of anti-proteasome autoantibodies (ng/ml)	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the daily number of new lesions	For patients suffering from bullous pemphigoid or pemphigus: the daily number of new lesions for the 3 days preceding blood sampling	baseline
Presence/absence of mucosal disease	For patients suffering from bullous pemphigoid only	baseline
Disease duration (weeks)	For patients suffering from bullous pemphigoid or pemphigus or lupus	baseline
% surface area	For patients suffering from bullous pemphigoid or pemphigus or lupus: % of skin area affected in relation to total area	baseline
Puritis score	For patients suffering from bullous pemphigoid only: severity of itching on a analog scale varying from 0 to 6	baseline
concentration of anti-PB18 antibodies, measured by ELISA	For patients suffering from bullous pemphigoid only; U/ml	baseline
Immunohistochemistry	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)	baseline
Tissue DNA expression	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)	baseline
presence/absence of oral lesions	For patients suffering from pemphigus	baseline
Presence/absence of Nikolsky's sign	For patients with pemphigus only	baseline
Pemphigus disease area index	For patients with Pemphigus only; score varying from 0 to 120.	baseline
Anti-desmogleine 1 and 3 antibody concentrations	For patients with Pemphigus only; ELISA (U/ml	baseline
CLASI score for lupus	for lupus patients only; score varying from 0 to 70	baseline
Karnofsky's score (%)		baseline
Plasma proteasome concentration	ng/ml	baseline
% trypsin-like plasma proteasome proteolytic activity		baseline
% chymotrypsin-like plasma proteasome proteolytic activity		baseline
% caspase-like plasma proteasome proteolytic activity		baseline

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Pierre Stoebner, MD, Centre Hospitalier Universitaire de Nīmes

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 5, 2013
• Primary Completion (ACTUAL): June 9, 2015
• Study Completion (ACTUAL): June 9, 2015

Study Registration Dates

• First Submitted: March 19, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (ESTIMATE): March 21, 2012

Study Record Updates

• Last Update Posted (ACTUAL): May 11, 2018
• Last Update Submitted That Met QC Criteria: May 4, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: disease activity; autoantibodies; proteasomes; proteasome concentration; proteolytic activity; proteasome autoantibody
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Connective Tissue Diseases; Skin Diseases, Vesiculobullous; Pemphigoid, Bullous; Autoimmune Diseases; Lupus Erythematosus, Cutaneous; Pemphigus
• Other Study ID Numbers: LOCAL/2011/PS-02; 2012-A00180-43 (OTHER: RCB number)