Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Terminated

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

• Registration Number: NCT01559155
• Lead Sponsor: Centre Hospitalier Universitaire de Nīmes

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.

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 Timeline

• Study First Submitted: 2012-03-19
• Study First Submitted QC: 2012-03-20
• Study First Posted: 2012-03-21
• Study Start: 2013-11-05
• Primary Completion: 2015-06-09
• Study Completion: 2015-06-09
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-04
• Last Update Posted: 2018-05-11

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 14

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Plasmatic concentration of anti-proteasome autoantibodies (ng/ml)	baseline

Secondary Outcome Measures

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

Trial Locations

Locations (1)

CHU de Nîmes - Hôpital Universitaire Carémeau; 🇫🇷 Nîmes Cedex 09, France