title: Ultrastructure of acantholysis in pemphigus foliaceus re-examined from the current perspective.
abstract: BACKGROUND
  Pemphigus foliaceus (PF) is a chronic cutaneous autoimmune blistering disease that is characterized by superficial blistering of the skin, and according to the current perspective is caused by autoantibodies directed against desmoglein (Dsg) 1.
  
  
  OBJECTIVE
  To examine early acantholysis in the skin of patients with PF at an ultrastructural level.
  
  
  METHODS
  Two Nikolsky-negative (N-), five Nikolsky-positive (N+) and two lesional skin biopsies from immunoserologically defined patients with PF were studied by light and electron microscopy.
  
  
  RESULTS
  We found no abnormalities in N- PF skin, whereas all the N+ skin biopsies displayed intercellular widening between desmosomes, a decreased number of desmosomes and hypoplastic desmosomes in the lower epidermal layers. Acantholysis was present in two of five N+ biopsies, but only in the upper epidermal layers. The lesional skin biopsies displayed acantholysis in the higher epidermal layers. Hypoplastic desmosomes were partially (pseudo-half-desmosomes) or completely torn off from the opposing cell.
  
  
  CONCLUSIONS
  We propose the following mechanism for acantholysis in PF: initially PF IgG causes a depletion of nonjunctional Dsg1, leading to intercellular widening between desmosomes starting in the lower layers and spreading upwards. Depletion of nonjunctional Dsg1 impairs the assembly of desmosomes, resulting in hypoplastic desmosomes and a decreased number of desmosomes. In addition, antibodies might promote disassembly of desmosomes. In the upper layers of the epidermis, where Dsg3 is not expressed and cannot compensate for Dsg1 loss, ongoing depletion of Dsg1 will finally result in a total disappearance of desmosomes and subsequent acantholysis.
authors: Centre for Blistering Diseases, Department of Dermatology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. g.van.der.wier@umcg.nl
authors: G
authors: G
authors: van der Wier
authors: M F
authors: MF
authors: Jonkman
authors: H H
authors: HH
authors: Pas
authors: G F H
authors: GF
authors: Diercks
mesh_terms: D000051:Acantholysis / Q000276:immunology / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood; D001706:Biopsy; D051183:Desmoglein 1 / Q000276:immunology; D051184:Desmoglein 3 / Q000276:immunology; D003896:Desmosomes / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D010392:Pemphigus / Q000276:immunology / Q000473:pathology*; D012867:Skin / Q000648:ultrastructure*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D051183:Desmoglein 1; D051184:Desmoglein 3; D007074:Immunoglobulin G