Specific affinity between fibronectin and the epidermolysis bullosa acquisita antigen.
Autoantibodies in the skin and sera of patients with epidermolysis bullosa acquisita bind to a large matrix molecule within the lamina densa region of skin basement membrane. At the site of these immune complexes, the epidermis separates from the dermis, which creates a subepidermal blister just below the lamina densa. The target molecule for the autoantibodies is in close apposition to fibronectin, a major extracellular matrix molecule that is abundant in the upper dermis of skin. In this report, we show specific affinity between fibronectin and the 290,000-D chain of the epidermolysis bullosa acquisita antigen, and that this affinity is mediated by the gelatin/collagen-binding domain of fibronectin (Mr = 60,000). Since blistering in epidermolysis bullosa acquisita often occurs in the absence of clinical and histological inflammation, a direct interruption in the fibronectin-epidermolysis bullosa acquisita antigen bond may be involved in the pathogenesis of epidermal-dermal disadherence that occurs in this bullous disease.
D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D001665:Binding Sites; D001768:Blister / Q000473:pathology; D004820:Epidermolysis Bullosa / Q000276:immunology* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding
D001323:Autoantibodies; D001324:Autoantigens; D005353:Fibronectins; C044589:epidermolysis bullosa acquisita antigen