Clinical trial NCT01559155: Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid
Official title: Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid
Study type: OBSERVATIONAL
Overall status: TERMINATED
Conditions: Pemphigoid, Bullous
Pemphigus
Lupus Erythematosus, Cutaneous
Keywords: proteasomes
proteasome concentration
disease activity
proteolytic activity
autoantibodies
proteasome autoantibody
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2012-03-21
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
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).

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.

Eligibility 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

Primary outcomes:
measure: Plasmatic concentration of anti-proteasome autoantibodies (ng/ml)
timeFrame: baseline
Secondary outcomes:
measure: the daily number of new lesions
timeFrame: baseline
measure: Presence/absence of mucosal disease
timeFrame: baseline
measure: Disease duration (weeks)
timeFrame: baseline
measure: % surface area
timeFrame: baseline
measure: Puritis score
timeFrame: baseline
measure: concentration of anti-PB18 antibodies, measured by ELISA
timeFrame: baseline
measure: Immunohistochemistry
timeFrame: baseline
measure: Tissue DNA expression
timeFrame: baseline
measure: presence/absence of oral lesions
timeFrame: baseline
measure: Presence/absence of Nikolsky's sign
timeFrame: baseline
measure: Pemphigus disease area index
timeFrame: baseline
measure: Anti-desmogleine 1 and 3 antibody concentrations
timeFrame: baseline
measure: CLASI score for lupus
timeFrame: baseline
measure: Karnofsky's score (%)
timeFrame: baseline
measure: Plasma proteasome concentration
timeFrame: baseline
measure: % trypsin-like plasma proteasome proteolytic activity
timeFrame: baseline
measure: % chymotrypsin-like plasma proteasome proteolytic activity
timeFrame: baseline
measure: % caspase-like plasma proteasome proteolytic activity
timeFrame: baseline
Other outcomes:
Locations:
city: Nîmes Cedex 09
country: France
facility: CHU de Nîmes - Hôpital Universitaire Carémeau
Study officials:
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Pierre Stoebner, MD
role: PRINCIPAL_INVESTIGATOR
References: