LAD-1, THE LINEAR IGA BULLOUS DERMATOSIS AUTOANTIGEN, IS A NOVEL 120-KDA ANCHORING FILAMENT PROTEIN SYNTHESIZED BY EPIDERMAL-CELLS

This study characterizes a novel basement membrane component that is t he target of autoantibodies in patients with linear IgA bullous dermat osis, Tissue surveys showed that this protein localized to the epiderm al side of 1 M NaCl split skin and to basement membranes in cornea, or al mucosa, esophagus, intestine, kidney collecting ducts, ureter, blad der, urethra, and thymus, but was absent in lung, blood vessels, skele tal muscle, and nerve, Monoclonal antibody 123, which recognizes this protein, induced dermal-epidermal separation of human skin in situ, an d this protein was found, by immunoelectron microscopy, to localize ex clusively to anchoring filaments. This protein was secreted as a 120-k Da peptide from primary cultures of keratinocytes as determined by rad ioimmunoprecipitation. Monoclonal antibody 123 recognized this protein as a 120-kDa band from conditioned cell culture medium and a 97-kDa b and from human skin extracts as shown by immunoblot. Serum from five p atients with the autoimmune blistering disorder linear IgA bullous der matosis specifically recognized bands of 120 and 97 kDa from culture m edium and skin extracts, respectively, that were of identical electrop horetic migration to the bands recognized by monoclonal antibody 123, In summary, this study characterizes a novel anchoring filament protei n that is the target of linear IgA bullous dermatosis autoantibodies. Because monoclonal antibody 123 induces blistering of human skin, we h ypothesize that this protein functions to maintain dermal-epidermal co hesion and that autoantibodies in this disease are themselves pathogen ic, We propose LAD-1 as the name for this protein.