Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Sponsor

Centre Hospitalier Universitaire de Nīmes (Other)

Overall Status

Terminated

CT.gov ID

NCT01559155

Collaborator

(none)

Enrollment

Location

19.1

Actual Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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	Intervention/Treatment	Phase
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

Study Type:

Observational

Actual Enrollment :

14 participants

Observational Model:

Cohort

Time Perspective:

Cross-Sectional

Official Title:

Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Actual Study Start Date :

Nov 5, 2013

Actual Primary Completion Date :

Jun 9, 2015

Actual Study Completion Date :

Jun 9, 2015

Arms and Interventions

Arm	Intervention/Treatment
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

Primary Outcome Measures

Plasmatic concentration of anti-proteasome autoantibodies (ng/ml) [baseline]

Secondary Outcome Measures

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
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
concentration of anti-PB18 antibodies, measured by ELISA [baseline]
For patients suffering from bullous pemphigoid only; 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)
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)
presence/absence of oral lesions [baseline]
For patients suffering from pemphigus
Presence/absence of Nikolsky's sign [baseline]
For patients with pemphigus only
Pemphigus disease area index [baseline]
For patients with Pemphigus only; score varying from 0 to 120.
Anti-desmogleine 1 and 3 antibody concentrations [baseline]
For patients with Pemphigus only; ELISA (U/ml
CLASI score for lupus [baseline]
for lupus patients only; score varying from 0 to 70
Karnofsky's score (%) [baseline]
Plasma proteasome concentration [baseline]
ng/ml
% trypsin-like plasma proteasome proteolytic activity [baseline]
% chymotrypsin-like plasma proteasome proteolytic activity [baseline]
% caspase-like plasma proteasome proteolytic activity [baseline]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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