Question 14 of 16

(demo test)

Type VII collagen is mutated in recessive dystrophic epidermolysis bullosa and is the targeted auto-antigen in epidermolysis bullosa acquisita and bullous lupus erythematosus (Fassihi et al. Br J Dermatol 2005). Type VII collagen is the primary constituent of hemidesmosomal dermal anchoring fibers. 

The following are important basement membrane zone structures, including clinically relevant genetic defects and antibodies:

• A.  Laminin 332
• Antibodies: Cicatricial pemphigoid with increased malignancy risk (anti-epiligrin MMP)
• Genetic defect: Junctional epidermolysis bullosa-Herlitz, Junctional epidermolysis bullosa-non-Herlitz
• B.  a6b4 integrin
• Antibodies: antibodies to the b4 integrin subunit leads to ocular mucous membrane pemphigoid
• Genetic defect: Junctional epidermolysis bullosa with pyloric atresia
• C.  BP230 (BPAG1)
• Antibodies: Both BP180 and BP230 are targets of autoantibodies in pemphigoid, however, it is the NC16A domain of BPAG2 that is thought to be pathogenic in bullous pemphigoid
• D.  BP180 (BPAG2)
• Antibodies: Pemphigoid gestationis, bullous pemphigoid, mucous membrane pemphigoid (cicatricial), and linear IgA bullous dermatosis (LABD)
• Genetic defect: Non-Herlitz junctional epidermolysis bullosa
  
• E.  Desmosome
• Antibodies: Paraneoplastic pemphigus (envoplakin), Pemphigus foliaceus (desmoglein I), Pemphigus vulgaris (desmoglein III), and Subcorneal pustular dermatosis (desmocollin I)
• Genetic defect: Naxos (plakoglobin), Carvajal (desmoplakin I/II), Ectodermal dysplasia/skin fragility syndrome (band 6 protein and plakophilin), and Striate palmoplantar keratoderma (desmoglein I)
• F.  Type IV collagen (lamina densa)
• Antibodies: Goodpasture syndrome
• Genetic Defect: Alport syndrome
• G.  Type VII collagen (Anchoring fibers)
• Antibodies: EBA, bullous LE
• Genetic defect: Recessive dystrophic epidermolysis bullosa including transient bullous dermolysis of the newborn
• H.  Type I and Type III collagen
• Genetic defect: Ehlers-Danlos (Type I Collagen)

Clinical Pearl: Type VII collagen is mutated in recessive dystrophic epidermolysis bullosa and transient bullous dermolysis of the newborn (a rare form of dystrophic epidermolysis bullosa). It is also the targeted auto-antigen in epidermolysis bullosa acquisita and bullous lupus erythematosus.