Cicatricial pemphigoid: IgA and IgG autoantibodies target epitopes on bothintra- and extracellular domains of bullous pemphigoid antigen 180

Background Cicatricial pemphigoid (CP) is an autoimmune subepidermal bliste ring disease where autoantibodies target various components of the dermal-e pidermal junction, including the bullous pemphigoid antigen 180 (BP180). Objective We determined the exact specificity of circulating IgG and IgA au toantibodies to BP180 in a large number of CP patients. Methods Twenty-six consecutive CP sera were analysed by Western blotting us ing a panel of cell-derived and recombinant proteins covering the entire BP 180 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 re activity to this protein. With the combined use of the soluble BP180 ectodo main (LAD-1) and recombinant BP180 NC16A, 16 of these 19 CP sera (84%) targ eted BP180. IgG reactivity was preferentially found against NC16A, whereas IgA antibodies predominantly recognized LAD-1. Thirty-two per cent of the B P180-reative sera revealed reactivity with the intracellular domain of this protein. Conclusions Our findings demonstrate that autoantibodies in CP target epito pes on both extra- and intracellular domains of BP180 and highlight the imp ortance of testing for both IgG and IgA reactivity in these patients' sera.