97-KDA LINEAR IGA BULLOUS DERMATOSIS (LAD) ANTIGEN LOCALIZES TO THE LAMINA-LUCIDA OF THE EPIDERMAL BASEMENT-MEMBRANE

Linear IgA bullous dermatosis (LAD) is an autoimmune blistering diseas e in which IgA autoantibodies develop against the epidermal basement m embrane zone. Target antigens of the circulating autoantibodies are th ought to be heterogeneous, and their ultrastructural localization has not been fully elucidated. Previous studies with immunoblotting have d emonstrated that the 97-kDa autoantigen is detected most frequently in patients' sera and is thought to be a major LAD antigen. Although a r ecent report suggests that the 97-kDa antigen localized to the hemides mosomal plaques and the adjacent lamina lucida, discrepancies still ex ist among previous immunoelectron microscopic findings. To identify th e precise localization of the 97-kDa LAD antigen, we used two differen t low-temperature immunoelectron microscopic techniques. For immunolab eling, we selected five LAD sera that had a high titer of autoantibodi es against the 97-kDa LAD antigen. A post-embedding method with cryofi xation and freeze substitution failed to immunolabel the 97-kDa LAD an tigen. Cryoultramicrotomy with immunoelectron microscopy succeeded in preserving the antigenicity of the 97-kDa LAD antigen. In all cases, t he majority of labeling occurred in the lamina lucida beneath the hemi desmosomes. No specific labeling was observed in the hemidesmosomal at tachment plaques or the lamina densa or sublamina densa region, includ ing anchoring fibrils. These results indicate that the 97-kDa LAD anti gen is a component of the lamina lucida.