Atypical pemphigus: autoimmunity against desmocollins and other non-desmoglein autoantigens

In this review, we recap current knowledge about non-desmoglein autoantigens in atypical forms of autoimmune pemphigus. More than 50 keratinocyte proteins, including adhesion molecules, receptors and enzymes as well as mitochondrial proteins can be targeted, leading to alterations in numerous intracellular signaling pathways. Patients with pemphigus herpetiformis feature various combinations of antibodies to desmogleins 1 and 3 and desmocollins 1-3. Pemphigus vulgaris patients who do not have antibodies to desmogleins develop typical clinical and histological features of pemphigus. Experimental results revealed synergy of different autoantibodies. Alterations of the keratinocyte adhesive function caused by a single antibody alone are reversible due to self-repair. Since composition of the pool of the most common pathogenic antibodies appears to be similar among pemphigus patients with or without antidesmoglein antibodies, the atypical pemphigus represents a unique model for elucidation of the molecular mechanisms of autoimmunity against non-desmoglein antigens. Further studies of the immunopathology of atypical pemphigus should shed new lights on the pathophysiology of conventional variants of autoimmune pemphigus.