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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

BP180 as the common autoantigen in blistering diseases with different clinical phenotypes.

Bullous pemphigoid antigen 180 (BP180, type XVII collagen) is a transmembrane hemidesmosomal glycoprotein of basal keratinocytes that spans the lamina lucida of the dermal-epidermal junction. Five autoimmune subepidermal blistering diseases are associated with an immune response to BP180, including bullous pemphigoid (BP), pemphigoid gestations (PG), cicatricial pemphigoid (CP), lichen planus pemphigoides (LPP), and linear IgA disease (LAD). The BP180 ectodomain consists of 15 interrupted collagen domains. The largest non-collagenous (NC) 16A domain is located next to the cell membrane. In BP, autoantibodies are directed to a tightly clustered set of epitopes located at the N-terminal 45 amino acids of the NC16A domain. However, some BP sera also react with other portions of the BP180 ectodomain or with the intracellular region of this protein. In PG, antibodies appear to exclusively recognize the immunodominant BP180 NC16A region. In CP, autoantibodies are directed to both the NC16A domain and the C-terminus of BP180 that projects into the lamina lucida/lamina densa interface of the dermal-epidermal junction. In LPP, autoantibodies react with an epitope located at the C-terminus of NC16A, that is not targeted by BP or PG sera. Finally, the epidermal 97 kDa and the keratinoctye-derived 120 kDa autoantigens of LAD (LABD97 and LAD-1, respectively) have recently been identified as portions of the BP180 ectodomain. These observations demonstrate that different clinical phenotypes are associated with an autoimmune response to the same autoantigen yet the immunoglobulin subclass of the autoantibody and the epitope that is recognized may be different.[1]


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