Molecular mechanisms of pathogenesis

The first clue to the etiology of pemphigus was established in 1964, when Beutner and Jordon¹ demonstrated that serum from pemphigus patients contained autoantibodies that bound to an intercellular substance (ICS) of skin and mucosa. Subsequently, skin biopsies revealed in vivo deposition of auto-antibodies in the epidermis of pemphigus patients.² While these results were intriguing, they did not prove that antibody played a role in the acantholytic process. The following three lines of evidence do support a role for antibody in the induction of acantholysis in pemphigus: correlation of antibody titers with disease activity^3,4; induction of acantholytic lesions in the skin of neonatal mice⁵ or in grafts of human oral mucosa on nude mice⁶ following passive transfer of patient IgG; and induction of acantholytic lesions in expiants of normal human skin following incubation with patient IgG.^7,8 The first two lines of evidence have been discussed in other chapters of this volume. It is our intention to describe experimental results from several laboratories confirming the pathologic events induced in normal human skin by serum or IgG preparations from pemphigus patients and to discuss the molecular events leading to the pathophysiology of pemphigus.