Antigen mimicry, epitope spreading and the pathogenesis of pemphigus.

The molecular and cellular pathogenesis of pemphigus remains unclear. However, the integrity of intraepidermal and dermoepidermal adhesion appears to be of special importance, and the presence of antibodies directed against desmosomal plaque proteins can provoke pemphigus-like pathologies. Antibodies reactive with various tissue antigens have been detected in pemphigus-like skin conditions. Two major factors determining the occurrence of different pemphigus subforms are antigen mimicry and epitope spreading, as these two phenomena underpin antibody generation in response to different antigens. This multiplicity of target antigens and antibody responses may lead to diagnostic problems early in the disease and may also explain the apparent transformation of one disease subform into another as time progresses.