Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on both intra- and extracellular domains of bullous pemphigoid antigen 180.
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.
Schmidt
E
E
Department of Dermatology, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany.
Skrobek
C
C
Kromminga
A
A
Hashimoto
T
T
Messer
G
G
Bröcker
E B
EB
Yancey
K B
KB
Zillikens
D
D
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
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