OCULAR CICATRICIAL PEMPHIGOID ANTIGEN - PARTIAL SEQUENCE AND BIOCHEMICAL-CHARACTERIZATION

Ocular cicatricial pemphigoid (OCP) is an autoimmune disease that affe cts mainly conjunctiva and other squamous epithelia, OCP is histologic ally characterized by a separation of the epithelium from underlying t issues within the basement membrane zone, Immunopathological studies d emonstrate the deposition of anti-basement membrane zone autoantibodie s in vivo. Purified IgG from sera of patients with active OCP identifi ed a cDNA clone from a human keratinocyte cDNA library that had comple te homology with the cytoplasmic domain of beta 4-integrin, The sera r ecognized a 205-kDa protein in human epidermal, human conjunctiva, and tumor cell lysates that was identified as beta 4-integrin by its reac tion with polyclonal and monoclonal antibodies to human beta 4-integri n. Sera from patients with bullous pemphigoid. pemphigus vulgaris, and cicatricial pemphigoid-like diseases did not recognize the 205-kDa pr otein, indicating the specificity of the binding, These data strongly implicate a role for human beta 4-integrin in the pathogenesis of OCP, It should be emphasized that multiple antigens in the basement membra ne zone of squamous epithelia may serve as targets for a wide spectrum of autoantibodies observed in vesiculobullous diseases, Molecular def inition of these autoantigens will facilitate the classification and c haracterization of subsets of cicatricial pemphigoid and help distingu ishing them from bullous pemphigoid, This study highlights the functio n and importance of beta 4-integrin in maintaining the attachment of e pithelial cells to the basement membrane.