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.