A specific antigen-antibody interaction triggers the cellular pathophysiology of bullous pemphigoid.

Autoantibodies found in both the skin and sera of patients with bullous pemphigoid (BP) are capable of initiating the pathophysiology of blister formation that occurs in this disease. Current concepts of the pathophysiology of BP suggest that antibody alone cannot cause blister formation, but that antibody acts through complement-fixation, degranulation of mast cells and subsequent recruitment of leukocytes to the epidermal basement membrane. These leukocytes then release proteolytic enzymes which result in dermal-epidermal separation. This paper addresses the question of whether a specific molecule in the basement membrane zone is involved in the antigen-antibody reaction which triggers the cellular pathophysiology of BP. Immunoprecipitates of extracts of cultured human or mouse epidermal cells, radiolabelled with either [35S]methionine or 14C-labelled amino acids, indicated that sera from 25 of 26 BP patients precipitated the same molecule, as determined by co-migration on sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE). This molecule is a protein with a mol. wt. of approximately 230 kd. A similar protein was identified in SDS extracts of normal human epidermis, as determined by immunoperoxidase staining of proteins separated by SDS-PAGE, then electrophoretically transferred to nitrocellulose sheets. Thus, in almost all cases of BP, one specific molecule of the epidermal basement membrane is involved in the antigen-antibody interaction that triggers the cellular pathophysiology of blister formation.