BP180 (type XVII collagen) and its role in cutaneous biology and disease.

BP180 is a key component of the epidermal anchoring complex and functions to maintain adherence of the epidermis to the basement membrane. Structural studies have revealed that BP180 is a type II transmembrane protein with a long carboxy-terminal collagenous domain that projects into the extracellular region beneath the epidermal hemidesmosome. The collagenous domains have the characteristic tripeptide repeat, Gly-X-Y. A normal proteolytic processing event results in the shedding of the BP180 extracellular domain (LAD1) from the keratinocyte cell surface. The biologic relevance of this process is not yet known. The interactions of BP180 with other constituents of the anchoring complex have been extensively studied and underscore the importance of BP180 in the assembly and functioning of this cell-matrix adhesion structure. In addition to its role in maintaining the integrity of the dermal-epidermal junction, there is evidence that BP180 is involved in transmembrane signal transduction and in the regulation of keratinocyte differentiation. BP180 mutations are responsible for certain forms of JEB and a rare subform of epidermolysis bullosa simplex. In addition, 5 acquired blistering disorders (i.e. BP, HG, CP, LAD and LPP) are associated with an autoimmune response to BP180. In vivo and in vitro disease model systems have clearly established the pathogenic relevance of autoantibodies directed against specific sites on the BP180 extracellular domain. Molecular and cellular analyses of the autoimmune response in BP and HG have been unable to distinguish these 2 diseases, supporting the notion that HG can be considered a pregnancy-associated form of BP. In contrast, the anti-BP180 immune response of the other 3 disease--CP, LAD, and LPP--can be immunologically distinguished from BP and HG. The distinctions lie within the isotype and subclass of the autoantibodies, as well as in differences in their fine specificities or complement-fixing properties, or both. These differences are thought to account for the heterogeneous phenotypes observed in this family of autoimmune diseases.