Defective in vivo expression and apparently normal in vitro expression of a newly identified 105-kDa lower lamina lucida protein in dystrophic epidermolysis bullosa.

We have previously identified a novel 105-kDa lower lamina lucida protein detected by the autoantibodies from a group of patients who developed a unique immune-mediated subepidermal bullous dermatosis. We sought to determine if this novel basement membrane zone (BMZ) protein is normally expressed in the skin of patients with various subsets of epidermolysis bullosa (EB). Indirect immunofluorescence microscopy performed on non-lesional skin sections from patients with three major EB subsets revealed absence or significantly reduced expression of this novel BMZ protein in 20 out of 23 skin sections from patients with generalized dominant and recessive dystrophic EB. However, immunoblot analyses with the autoantibodies on Western-blotted proteins revealed that a comigrating 105-kDa protein is present in both cytosol extracts (n = 6) and conditioned media (n = 3) of cultured dermal fibroblasts derived from patients with dystrophic EB, as well as those cultured from two healthy individuals. Although the reason for such disparate findings is not known, the defective in vivo expression of this novel 105-kDa protein in dystrophic EB is presumably not due to a failure of fibroblasts to synthesize or secrete the protein. It is possible, however, that the 105-kDa protein may be unable to incorporate into the BMZ because it is produced in a dysfunctional form, or its BMZ binding site is missing. It is also possible that other structural alterations in skin BMZ, which occur in dystrophic EB, result in masking of the antigenic binding by the autoantibody when intact BMZ is probed.(ABSTRACT TRUNCATED AT 250 WORDS)