A Bullous Skin Disease Patient With Autoantibodies Against Separate Epitopes in 1 mol/L Sodium Chloride Split Skin

Background.—We describe a patient with a subepidermal bullous skin disease associated with autoantibodies recognizing separate epitopes in 1 mol/L sodium chloride (NaCl) split skin. Observations.—Direct immunofluorescence microscopy showed deposits of immunoglobulins and C3 in a continuous pattern in the patient's epidermal basement membrane zone. Direct immunoelectron microscopy demonstrated thick deposits of IgG overlying the lamina lucida and the lamina densa in a unique pattern. The patient had circulating IgG anti— basement membrane zone antibodies that bound both sides of 1 mol/L NaCl split skin, exhibited at least a fourfold-higher titer against the dermal side of this test substrate, and bound basal keratinocyte hemidesmosomes as well as focal sites along the superior portion of the lamina densa on indirect immunoelectron microscopy. Affinity purification of anti—base-ment membrane zone antibodies against epidermal or dermal strips of 1 mol/L NaCl split skin yielded IgG that only bound the side of split skin from which it was eluted. The patient's serum contained IgG that immunoprecipitated and immunoblotted the 230- and 170-kd bullous pemphigoid antigens. Affinity purification of patient antibody against bullous pemphigoid antigen immobilized on nitrocellulose paper yielded IgG that bound only the epidermal side of 1 mol/L NaCl split skin. The patient showed no evidence of reactivity against type VII collagen by direct immunoelectron microscopy, indirect immunoelectron microscopy, or immunoblot. Conclusions.—This patient's bullous skin disease is associated with IgG anti—basement membrane zone antibodies with two specificities: one recognizing the bullous pemphigoid antigen in the epidermal side of 1 mol/L NaCl split skin, and another binding a distinct, yet presently unidentified, epitope in the superior aspect of the lamina densa.