Isolation of a human epidermal cDNA corresponding to the 180-kD autoantigen recognized by bullous pemphigoid and herpes gestationis sera. Immunolocalization of this protein to the hemidesmosome.

Abstract

Autoantibodies present in the sera of patients with bullous pemphigoid (BP) bind to the basement membrane zone of normal human skin and commonly recognize two epidermal proteins, the BP240 and BP180 antigens. Two BP antigen cDNA clones from a lambda gtl1 human keratinocyte library have been identified on the basis of reactivity with a BP serum. The fusion protein (FP) produced by one clone immunoadsorbed autoantibodies, which specifically recognized the BP180 antigen, showing no cross-reactivity with BP240 by immunoblot analysis. The FP produced by the second clone immunoadsorbed autoantibodies which specifically reacted with the BP240 epidermal antigen. Northern blot analysis demonstrated that the BP180 and BP240 antigens are encoded by distinct RNA transcripts with lengths of 6.0 and 8.5 kb, respectively. Immunoblot analysis of the BP180 lysogen extract identified a 135-kD FP which was recognized by 7 of 16 BP sera and 7 of 8 herpes gestationis sera. A rabbit antiserum prepared against the lysogenic BP180 FP specifically recognized the BP180 antigen from human epidermal extracts by immunoblotting, labeled the BMZ by indirect immunofluorescence, and bound to human epidermal hemidesmosomes by immuno-electron microscopy. These results indicate that the BP180 antigen recognized by BP and herpes gestationis autoantibodies is a unique hemidesmosomal polypeptide, distinguishable from the BP240 antigen. (J. Clin. Invest. 1990.

The C5a Receptor on Mast Cells Is Critical for the Autoimmune Skin-blistering Disease Bullous Pemphigoid

“…Bullous pemphigoid (BP) 3 is an acquired autoimmune skinblistering disease characterized by the presence of circulating and tissue-bound autoantibodies against two major hemidesmosomal proteins, BP230 (BPAG1) and BP180 (BPAG2 or type XVII collagen) (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11). These anti-hemidesmosomal autoantibodies, along with complement components, are deposited along the basement membrane at the dermal-epidermal junction of perilesional skin (12)(13)(14).…”

The α5 Chain of Type IV Collagen Is the Target of IgG Autoantibodies in a Novel Autoimmune Disease with Subepidermal Blisters and Renal Insufficiency

“…Three collagen types have been shown thus far to be the target of autoimmune response in human pathologies: (i) the NC1 domain of ␣3 chain of type IV collagen in Goodpasture syndrome (2), (ii) the NC1 domain of type VII collagen in epidermolysis bullosa acquisita (EBA) 1 (3), and (iii) a noncollagenous segment of type XVII collagen in bullous pemphigoid (BP) (4). The ␣3(IV) collagen chain, present in glomerular and alveolar basement membranes, is the target antigen in Goodpasture syndrome, a lethal form of autoimmune disease characterized by glomerulonephritis and pulmonary hemorrhage.…”

Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles

“…As noted above, the epidermis of dt/dt mutant mice resembles that of bullous pemphigoid, a human disorder where autoantibodies against BPAG1 are produced (Diaz et al, 1990;Labib et al, 1986;Mueller et al, 1989). A BPAG1e-specific mutation has been found in humans with an inherited skin fragility disorder (Groves et al, 2010).…”

“…In the epidermis, loss of BPAG1e leads to a selective fragility of the base of the columnar basal cells, resulting in blisters and compromised wound healing (Guo et al, 1995). The phenotype of mice with an epidermal-specific deletion of BPAG1 resembles that of bullous pemphigoid, a human skin disease in which patients produce autoantibodies against BPAG1 (Labib et al, 1986;Mueller et al, 1989;Diaz et al, 1990). Mutations in BPAG1 have also been found in humans with an inherited skin fragility disorder (Groves et al, 2010).…”