Certain skin basement membrane components, such as
bullous pemphigoid antigens and
epidermolysis bullosa acquisita antigen, were discovered as a result of an autoimmune reaction. In this report, we describe a unique lamina lucida determinant associated with a novel immune-mediated subepidermal bullous
dermatosis. This unique bullous
dermatosis resembled severe
toxic epidermal necrolysis clinically. The histologic findings resemble
dermatitis herpetiformis. Direct immunofluorescence microscopy detected linear
immunoglobulin G (
IgG) and C3 deposition at the cutaneous basement membrane zone of lesional and perilesional skin. Direct and indirect immunoelectron microscopy localized the
IgG deposits to the lowest portion of the lamina lucida. The patient's
autoantibodies, belonging to the
IgG1 subclass, labeled basement membrane zone of normal intact human skin, oral mucosa, and conjunctiva, and localized to the dermal side of
salt-split normal adult and neonatal human skin, but failed to react with human fetal skin up to 142 gestational days. The patient's
autoantibodies failed to react with
bullous pemphigoid antigens or
epidermolysis bullosa acquisita antigen (
type VII collagen) by immunoblotting. Instead, the patient's
autoantibodies unequivocally labeled a 105-kilodalton (kD)
protein in cellular extracts and
conditioned media of human cultured keratinocytes and dermal fibroblasts. The titer of the patient's antibody against the cutaneous basement membrane zone and the intensity of the antibody reactivity against the 105-kD
protein paralleled the patient's disease activity. Thus, this 105-kD lower lamina lucida
protein represents a novel
autoantigen and this patient's disease represents a novel
autoantigen and this patient's disease represents a deep lamina lucida
pemphigoid, distinguishable from all other known autoimmune
bullous dermatoses.