title: Autoantibodies to the extracellular and intracellular domain of bullous pemphigoid 180, the putative key autoantigen in bullous pemphigoid, belong predominantly to the IgG1 and IgG4 subclasses.
abstract: BACKGROUND
  Autoantibodies to the extracellular domain (ECD) of bullous pemphigoid (BP) antigen 180 (BP180) are thought to play a crucial part in the pathophysiology of BP.
  
  
  OBJECTIVE
  As the various IgG subclasses have different biological properties, we have sought to assess the relative isotype distribution of IgG to BP180 and their reactivity against the ECD and intracellular domain (ICD) of BP180.
  
  
  METHODS
  The reactivity of 27 sera from patients with BP was assayed by immunoblotting against recombinant proteins covering the ECD and ICD of BP180.
  
  
  RESULTS
  Twenty-seven (100%) and 21 (77%) of 27 BP sera, respectively, contained IgG1 and IgG4 autoantibodies binding to the ECD of BP180. Fourteen (82%) and six (35%) of the 17 BP sera that were reactive with the ICD of BP180 had autoantibodies of the IgG1 and IgG4 subclass, respectively. The profile of the isotype restriction appeared to be similar when the response to the ECD vs. that to the ICD was compared. IgG2 and IgG3 reactivity with BP180 was found less frequently. Patients with BP of longer duration showed a tendency to have, in addition to IgG1, an IgG4 response.
  
  
  CONCLUSIONS
  Consistent with prior evidence indicating that subepidermal blister formation in BP is dependent upon complement activation, the frequent finding of complement-fixing IgG1 autoantibodies to both the ECD and ICD of BP180 might have pathogenic relevance in BP. These findings provide new insights relevant for our understanding of the immune response to BP180, the putative key autoantigen in BP.
authors: Clinique de Dermatologie, Hôpital Cantonal Universitaire, Rue Micheli du Crest 26, CH-1211 Geneva, Switzerland.
authors: E
authors: E
authors: Laffitte
authors: M
authors: M
authors: Skaria
authors: F
authors: F
authors: Jaunin
authors: K
authors: K
authors: Tamm
authors: J H
authors: JH
authors: Saurat
authors: B
authors: B
authors: Favre
authors: L
authors: L
authors: Borradori
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007223:Infant; D008875:Middle Aged; D024041:Non-Fibrillar Collagens; D010391:Pemphigoid, Bullous / Q000276:immunology* / Q000473:pathology; D011994:Recombinant Proteins / Q000276:immunology; D013997:Time Factors; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D024041:Non-Fibrillar Collagens; D011994:Recombinant Proteins; D000097805:Collagen Type XVII