Autoantibodies in lichen planus pemphigoides react with a novel epitope within the C-terminal NC16A domain of BP180

Lichen planus pemphigoides is an autoimmune subepidermal blistering disease , The finding of immunoglobulin G antibodies directed against the basement membrane zone differentiates it from bullous Lichen planus, The aim of this study was to identify the target antigen of lichen planus pemphigoides aut oantibodies. Sera from lichen planus pemphigoides patients (n = 4) stained the epidermal side of NaCl-split human skin in a pattern indistinguishable from that produced by bullous pemphigoid sera. In bullous pemphigoid, the a utoimmune response is directed against BP180, a hemidesmosomal transmembran e collagenous glycoprotein, We previously demonstrated that bullous pemphig oid sera predominantly react with a set of four epitopes (MCW-0 through MCW -3) clustered within a 45 amino acid stretch of the major noncollagenous ex tracellular domain (NC16A) of BP180, By immunoblotting and enzyme-linked im munosorbent assay, lichen planus pemphigoides sera were also strongly react ive with recombinant bullous pemphigoid 180 NC16A, The Lichen planus pemphi goides epitopes were further mapped using a series of overlapping recombina nt segments of the NC16A domain. All lichen planus pemphigoides sera reacte d with amino acids 46-59 of domain NC16A, a protein segment that was previo usly shown to be unreactive with bullous pemphigoid sera, Two lichen planus pemphigoides sera, in addition, reacted with the immunodominant antigenic region associated with bullous pemphigoid, In conclusion, there are now fiv e bullous diseases that are associated with an autoimmune response to BP180 : bullous pemphigoid; pemphigoid/herpes gestationis; cicatricial pemphigoid ; linear immunoglobulin A disease; and lichen planus pemphigoides. In addit ion, we have identified a novel epitope within the BP180 NC16A domain, desi gnated MCW-4, that appears to be uniquely recognized by sera from patients with Lichen planus pemphigoides.