188 DISEASES/DISORDERS
Components of desmosomes and hemidesmosomes may be targets of autoim-
munity, and include:
Plakins (e.g., desmoplakin, bullous pemphigoid antigen 1): proteins that
anchor filaments to desmosomal plaques
Armadillo protein (e.g., plakophilin, plakoglobin): structural and signaling
proteins that share repeated amino acid sequences
Cadherins (e.g., desmoglein1–4, desmocollin1–3): transmembrane,
calcium-dependent adhesion proteins
Plectin: links components of cytoskeleton (actin microfilaments, micro-
tubules, intermediate filaments) in hemidesmosomes
Integrins: heterodimers with alpha and beta subunits; transmembrane
receptor glycoproteins that mediate adhesion
Laminin (specifically laminin 5): structural glycoproteins in the extracellu-
lar matrix (with alpha, beta, and gamma chains)
Collagen (type VII and XVII): transmembrane structural components
(anchoring fibrils) of hemidesmosomes.Autoimmune blistering diseases: circulating autoantibodies (most commonly IgG)
bind to structural components to induce cell separation within desmosomes of the
epidermis or hemidesmosomes at the basement membrane zone (BMZ).Acantholysis: disruption of desmosomes causing keratinocyte separation; disruption
of hemidesmosomes causes blistering beneath the epidermis and thus does not cause
acantholysis.Acantholysis may have genetic, infectious (proteolytic), or autoimmune causes.
Binding of autoantibodies causes steric hindrance (direct interference with function),
triggering of (or impaired) transmembrane signaling resulting in desmosome deple-
tion, and/or reduction of acetylcholine-induced phosphorylation leading to abnormal
desmosome production.Loss of intracellular cohesion produces vesicles, pustules, and/or bullae.
Severity of erosion, ulceration, and disease: related to location of autoantibody depo-
sition (specific structure molecule targeted) within or beneath the epidermis.
Pemphigus Complex
PF: precise autoantibody antigen unknown but targets the superficial epidermis; some
cases demonstrate anti-desmoglein (Dsg) 1 IgG.
PE: autoantibody targets Dsg1 and antigens expressed on epidermal cells following
ultraviolet light exposure.
PV: autoantibody targets Dsg3; additional targeting of Dsg1 with mucosal lesions.
PEP/Pveg: autoantibody targets Dsg1 (suggesting PEP is a more severe variant of PF
and not PV as in humans).
PP: autoantibody targets Dsg3, desmoplakin, and possibly plakoglobin.
Implicated trigger factors are varied: genetics, hormones, neoplasia, drugs, nutrition,
viral, emotional stress, and physical factors (burns, UV radiation).
Pemphigus may be drug induced (directly initiate acantholysis) or drug triggered
(cause symptomatic disease in predisposed individuals).