Role of Proteasomes in a Dermatological Autoimmune Disease: Bullous Pemphigoid

• 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 ]

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.

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.

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).

• Pemphigoid, Bullous
• Pemphigus
• Lupus Erythematosus, Cutaneous

• 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.

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

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
• patient has not started treatment

For the pemphigus group:

• patient with pemphigus
• patient has not started treatment

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
• the patient has not started treatment

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 has started treatment for his/her autoimmune disease

For the controls:

• autoimmune disease
• inflammatory disease
• evolving neoplastic disease
• surgery during the last 6 months