A 65-year-old man has developed pruritus followed by blistering skin lesions over the trunk, legs, and arms over the past month. On physical examination, there are 1- to 4-cm tense bullae, particularly over flexural surfaces of the skin. A biopsy of one lesion is examined microscopically by direct immunofluorescence staining and shows a subepidermal bulla, with both IgG and C3 deposited linearly along the dermal-epidermal junction. He is treated with topical corticosteroids, and a month later the lesions are healed without scarring. Which of the following components of the skin has most likely been targeted by an autoantibody in this man?

Subepidermal bullae of bullous pemphigoid usually heal without scarring. Subsequent oral lesions may appear. Most often seen in the elderly, this disease results from linear IgG deposition at the basal cell-basement membrane attachment plaques (hemidesmosomes) containing bullous pemphigoid antigen (BPAG). The lamina densa of the basement membrane is not directly involved, and the actual blister of bullous pemphigoid forms in the lamina lucida. In contrast, the antibodies in pemphigus vulgaris attack the desmosomes that attach the epidermal keratinocytes. Antibodies directed against nuclear antigens are more typical for systemic autoimmune diseases such as systemic lupus erythematosus. The antigliadin antibodies of dermatitis herpetiformis cross-react with dermal reticulin, and there are micro abscesses at the tips of dermal papillae.