Mapping of epitopes on the BP180 ectodomain targeted by IgA and IgG antoantibodies in patients with the lamina lucida-type of linear IgA disease

Linear IgA disease (LAD) is an autoimmune subepidermal blistering skin dise ase characterized by the linear deposition of IgA at the dermoepidermal jun ction. Serum from patients with LAD most commonly contains autoantibodies t hat are directed against the hemidesmosomal transmembrane glycoprotein BP18 0 (type XVII collagen). Various antigenic sites on the extracellular domain of this anchoring filament protein have been shown to be targeted by autoa ntibodies in different autoimmune bullous skin diseases, including bullous pemphigoid and cicatricial pemphigoid (CP), However, little is known about epitopes on BP180 recognized by autoantibodies in LAD. In this study, we us ed three recombinant GST fusion proteins, together roughly covering the ent ire BP180 ectodomain, to characterize the autoimmune response in serum from patients with LAD. Interestingly, we found both IgA and IgG reactivity to all three portions of the BP180 ectodomain, The strongest reactivity was ob served with the C-terminal portion of BP180, This is also the major region recognized by autoantibodies in patients with CP, This finding correlates w ith the observation that there may be significant overlap of the clinical a nd immunopathological findings in LAD and CP.