Autoimmune Blistering Diseases Overview

Autoimmune Blistering Diseases

• Chronic, debilitating conditions causing skin and/or mucous membrane blisters or erosions.
• Some are fatal if untreated.
• Classification based on clinical features (lesion distribution, morphology).
• Pemphigus and pemphigoid are the most common types.

Pemphigus Subtypes

• Pemphigus vulgaris (PV):
  • Characterized by flaccid bullae/erosions affecting skin and mucous membranes.
  • Targets desmoglein 3 (Dsg3) as the primary autoantigen.
  • Often presents with oral/esophageal lesions first, then skin.
• Pemphigus foliaceous (PF):
  • Affects only the skin, presenting with fragile blisters or superficial erosions.
  • Targets desmoglein 1 (Dsg1) as the primary autoantigen.
  • Typically presents only in the skin.
• Other rare forms:
  • IgA pemphigus (IgA autoantibodies against desmocollin 1, Dsg1 or Dsg3)
  • Paraneoplastic pemphigus (autoantibodies against multiple desmosomal proteins plus T cells)

Bullous Pemphigoid (BP)

• Characterized by:

  • Urticarial lesions progressing to tense bullae on skin.
  • Less commonly, mucous membrane erosions.

• Primarily targets hemidesmosomal components.

• Primary autoantigens:

  • Collagen XVII (COL17, BP180).
  • Plakin family protein BP230 (BPAG2).

• COL17 (BP180) is the major target.

• Complement (C3) deposition crucial for blister formation in BP.

Diagnostic Methods

• Routine histology and immunofluorescence microscopy for diagnosis.
• Enzyme-linked immunosorbent assays (ELISAs) detect circulating autoantibodies.

Mechanisms and Treatment

• Autoimmune mechanisms: Loss of tolerance allowing the immune system to attack self-antigens.
• Treatment: Typically uses systemic glucocorticoids and/or immunosuppressive agents.
• Targeted therapies: Monoclonal antibody rituximab effective in targeting B cells in a targeted fashion reducing or eliminating relapses.

Disease Models

• Animal models (e.g., Dsg3 knockout [KO] mice) help study PV.
• Transfer of immune cells/molecules from these animal models helps elucidate the mechanisms of autoimmune blister formation.

Key antigens and their roles

• Desmogleins:
  • Dsg3 in PV impacts various mucosal surfaces.
  • Dsg1 in PF impacts merely epidermal locations.
• Collagen XVII (COL17):
  • In BP, crucial in linking basal keratinocytes to the basement membrane.
• BP230/BPAG2: Intracellular protein with an uncertain pathogenic role in BP.

Unique features of various blistering conditions

• Pemphigoid gestationis: Identical clinical features and autoantibody profiles as BP only in pregnant women
• Mucous membrane pemphigoid: Circulating antibodies target various basement membrane proteins.
• Epidermolysis bullosa acquisita: Primarily targets type VII collagen (COL7).