CICATRICIAL PEMPHIGOID AUTOANTIBODIES REACT WITH MULTIPLE SITES ON THE BP180 EXTRACELLULAR DOMAIN

Cicatricial pemphigoid (CP) is an autoimmune blistering disease that p rimarily affects mucosal tissues, Autoantibodies to laminin-5 have pre viously been detected in certain patients with a CP-like disease; howe ver, individuals that exhibit this reactivity profile apparently repre sent a small subset of CP patients. In the present investigation, 0 of 18 CP sera showed reactivity with laminin-5 by immunoblotting. In con trast, 18 of 23 CP sera (78%) recognized a 180-kDa epidermal antigen t hat, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, co- migrated with BP180, a hemidesmosomal glycoprotein associated with two other autoimmune blistering diseases, bullous pemphigoid and herpes g estationis. To investigate further the CP autoimmune response, various segments of human BP180 were expressed as bacterial fusion proteins a nd assayed by immunoblotting for reactivity with CP patients' sera, Th e results of this investigation demonstrated that the BP180 autoantige n is indeed a major target of CP autoantibodies, Further, two distinct CP-reactive sites were identified on the extracellular domain of the BP180 protein, one located in the non-collagenous (NC) 16A domain (at or near the previously defined autoantibody-reactive site recognized b y bullous pemphigoid and herpes gestationis sera) and the other in the carboxy-terminal region of this protein, Sixteen of 23 CP sera (70%) reacted with one or both of these antigenic sites of BP180, Other immu nologic data suggested that BP180 may harbor additional CP-reactive si tes, In conclusion, there are now three bullous diseases, bullous pemp higoid, herpes gestationis, and cicatricial pemphigoid, that are known to be associated with an autoimmune response against the extracellula r domain of the BP180 antigen.