title: Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180.
abstract: BACKGROUND
  Cicatricial pemphigoid (CP) is an autoimmune subepidermal blistering disease where autoantibodies target various components of the dermal-epidermal junction, including the bullous pemphigoid antigen 180 (BP180).
  
  
  OBJECTIVE
  We determined the exact specificity of circulating IgG and IgA autoantibodies to BP180 in a large number of CP patients.
  
  
  METHODS
  Twenty-six consecutive CP sera were analysed by Western blotting using a panel of cell-derived and recombinant proteins covering the entire BP180 molecule.
  
  
  RESULTS
  Circulating autoantibodies were detected in all CP sera. Seven sera reacting with laminin-5 were excluded from further analyses; the remaining 19 sera recognized BP180, including six sera (32%) that showed only IgA reactivity to this protein. With the combined use of the soluble BP180 ectodomain (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targeted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the BP180-reative sera revealed reactivity with the intracellular domain of this protein.
  
  
  CONCLUSIONS
  Our findings demonstrate that autoantibodies in CP target epitopes on both extra- and intracellular domains of BP180 and highlight the importance of testing for both IgG and IgA reactivity in these patients' sera.
authors.affiliation: Department of Dermatology, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schmidt
authors.forename: C
authors.initials: C
authors.lastname: Skrobek
authors.forename: A
authors.initials: A
authors.lastname: Kromminga
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: G
authors.initials: G
authors.lastname: Messer
authors.forename: E B
authors.initials: EB
authors.lastname: Bröcker
authors.forename: K B
authors.initials: KB
authors.lastname: Yancey
authors.forename: D
authors.initials: D
authors.lastname: Zillikens
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015153:Blotting, Western; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules / Q000276:immunology; D015816:Cell Adhesion Molecules, Neuronal / Q000276:immunology; D003094:Collagen / Q000276:immunology*; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D000939:Epitopes / Q000276:immunology; D005260:Female; D015801:Helminth Proteins / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D024041:Non-Fibrillar Collagens; D010390:Pemphigoid, Benign Mucous Membrane / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D000097794:Kalinin; D000097805:Collagen Type XVII
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D003094:Collagen; D003598:Cytoskeletal Proteins; D000071821:Dystonin; D000939:Epitopes; D015801:Helminth Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D024041:Non-Fibrillar Collagens; D011994:Recombinant Proteins; D000097794:Kalinin; D000097805:Collagen Type XVII; C486268:DST protein, human; C501528:SAX-7 protein, C elegans