Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Study Overview
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Brief Summary
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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
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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.

Official Title
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Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

Conditions
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Pemphigoid, Bullous, Pemphigus, Lupus Erythematosus, Cutaneous

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bullous pemphigoid<br>Patients in this cohort are newly diagnosed (or have not started treatment) with bullous pemphigoid | |
| Other bullous-like auto-immune<br>Patients in this cohort are newly diagnosed (or have not started treatment) with pemphigus (15 patients) or cutaneous lupus (15 patients) | |
| Control group<br>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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proteasomes, proteasome concentration, disease activity, proteolytic activity, autoantibodies, proteasome autoantibody