ANTIEPILIGRIN CICATRICIAL PEMPHIGOID - A SUBEPITHELIAL BULLOUS DISORDER

Background: Epiligrin is a glycoprotein complex deposited in extracell ular matrix by cultured human keratinocytes that serves as the major i ntegrin ligand of these cells. In human skin, epiligrin is found at th e interface of the lamina lucida and lamina densa in epidermal basemen t membrane where it is believed to be associated with anchoring filame nts and plays an important role in keratinocyte adhesion. Methods and Results: We have identified six patients with a subepithelial bullous disorder of mucous membranes and skin who have IgG anti-basement membr ane autoantibodies that immunoprecipitate epiligrin from human keratin ocyte extracts and culture media. These patients' IgG autoantibodies a lso bind epiligrin in human keratinocyte extracellular matrix and epid ermal basement membrane as determined by immunofluorescence and immuno electron microscopy. Studies of 10 patients who are clinically indisti nguishable from subjects with antiepiligrin autoantibodies (ie, cicatr icial pemphigoid patients) found that while seven had anti-basement me mbrane autoantibodies, the latter are directed exclusively against a r egion of epidermal basement membrane that does not contain epiligrin, are present in low titer (ie, less than or equal to 1:10), do not reac t with keratinocyte extracellular matrix, and do not bind epiligrin (o r any other specific antigen) in immunoprecipitation studies of human keratinocyte extracts or media. Antiepiligrin autoantibodies were also not detected in studies of 36 additional patients with bullous diseas es or six normal volunteers. Conclusions: Cicatricial pemphigoid is a disease phenotype in which patients' autoantibodies may target differe nt constituents of epidermal basement membrane. Antiepiligrin autoanti bodies are a specific immunologic marker for a group of patients with a disease entity that we propose to designate antiepiligrin cicatricia l pemphigoid.