Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid - Full Text View

Purpose

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
Pemphigoid, Bullous Pemphigus Lupus Erythematosus, Cutaneous


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Cross-Sectional
Official Title:	Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Resource links provided by NLM:

MedlinePlus related topics: Autoimmune Diseases Pemphigus

Genetic and Rare Diseases Information Center resources: Bullous Pemphigoid Cutaneous Lupus Erythematosus Pemphigus

U.S. FDA Resources

Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:

Plasmatic concentration of anti-proteasome autoantibodies (ng/ml) [ Time Frame: baseline ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

the daily number of new lesions [ Time Frame: baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients suffering from bullous pemphigoid only
Disease duration (weeks) [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients suffering from bullous pemphigoid or pemphigus or lupus
% surface area [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients suffering from bullous pemphigoid or pemphigus or lupus: % of skin area affected in relation to total area
Puritis score [ Time Frame: baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients suffering from bullous pemphigoid only; U/ml
Immunohistochemistry [ Time Frame: baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline ] [ Designated as safety issue: No ]
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 [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients suffering from pemphigus
Presence/absence of Nikolsky's sign [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients with pemphigus only
Pemphigus disease area index [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients with Pemphigus only; score varying from 0 to 120.
Anti-desmogleine 1 and 3 antibody concentrations [ Time Frame: baseline ] [ Designated as safety issue: No ]
For patients with Pemphigus only; ELISA (U/ml
CLASI score for lupus [ Time Frame: baseline ] [ Designated as safety issue: No ]
for lupus patients only; score varying from 0 to 70
Karnofsky's score (%) [ Time Frame: baseline ] [ Designated as safety issue: No ]
Plasma proteasome concentration [ Time Frame: baseline ] [ Designated as safety issue: No ]
ng/ml
% trypsin-like plasma proteasome proteolytic activity [ Time Frame: baseline ] [ Designated as safety issue: No ]
% chymotrypsin-like plasma proteasome proteolytic activity [ Time Frame: baseline ] [ Designated as safety issue: No ]
% caspase-like plasma proteasome proteolytic activity [ Time Frame: baseline ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples With DNA

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


Estimated Enrollment:	130
Study Start Date:	November 2013
Estimated Study Completion Date:	November 2015
Estimated Primary Completion Date:	November 2015 (Final data collection date for primary outcome measure)

Groups/Cohorts
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.

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


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01559155

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

No publications provided


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
Study First Received:	March 19, 2012
Last Updated:	November 3, 2014
Health Authority:	France: Committee for the Protection of Personnes France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Centre Hospitalier Universitaire de Nīmes:


proteasomes proteasome concentration disease activity	proteolytic activity autoantibodies proteasome autoantibody

Additional relevant MeSH terms:


Autoimmune Diseases Lupus Erythematosus, Cutaneous Pemphigoid, Bullous Connective Tissue Diseases	Immune System Diseases Skin Diseases Skin Diseases, Vesiculobullous

ClinicalTrials.gov processed this record on March 03, 2015