The nature and expression pattern of the 97 kDa
linear IgA bullous dermatosis antigen (LAD-1) and its role in
epidermolysis bullosa have not been fully elucidated. In this study, we examined the expression of LAD-1 in the skin specimens of 70 patients with the various subtypes of
epidermolysis bullosa, including simplex (n = 23), junctional (n = 15), and dystrophic variants (n = 32). For immunolabeling, we used two recently developed
monoclonal antibodies to LAD-1 whose
epitopes were ultrastructurally localized in the lamina lucida between NC16A and carboxyterminal domains of BPAG2, as well as
autoantibodies against LAD-1 from the sera of two patients with
linear IgA dermatosis. Among the 70 patients, only one patient with generalized atrophic benign
epidermolysis bullosa failed to demonstrate LAD-1 expression. Although other major basement membrane components, including
laminin 5, BPAG1,
plectin, alpha6 and beta4
integrins, as well as type IV and type VII
collagens were normally expressed, BPAG2/
type XVII collagen was absent from the skin of this patient. Mutation analysis on COL17A1 using polymerase chain reaction amplification, heteroduplex scanning, and direct
nucleotide sequencing revealed that this patient was homozygous for a novel
nonsense mutation G258X in exon 11, and her parents were heterozygous carriers for this mutation. This is the first mutation located in the intracellular domain of BPAG2, and resides 817 bp upstream from the N-terminal amino acid sequence of LAD-1. These findings indicate that the absent expression of LAD-1 is observed in a BPAG2-deficient generalized atrophic benign
epidermolysis bullosa patient with mutations in both alleles of COL17A1, and not in other
epidermolysis bullosa subtypes. These findings also support the notion that LAD-1 is a degradation product of BPAG2.