A perspective of pemphigus from bedside and laboratory-bench.
Pemphigus represents a distinct organ-specific acquired autoimmune disease characterized by intra-epidermal blistering, which is induced by autoantibodies against desmosomal cadherins, desmoglein 1 (Dsg1), and Dsg3. Pemphigus is currently divided into three distinct varieties, i.e., pemphigus vulgaris (PV), pemphigus foliaceus (PF) and other variants of pemphigus (mostly associated with inflammation), depending on clinical features, the level of separation in the epidermis, and immunologic characteristics of auto-antigens. Blistering pathomechanisms differ for each of the types of pemphigus. Pemphigus, which results from autoantibodies against desmogleins and possibly to other proteins, binds to the cell surface antigens. This binding may cause steric hindrance to homophilic adhesion of desmogleins, and may, in turn, lead to internalization of desmogleins and inhibition of desmogleins' integration into desmosomes, resulting in the formation of Dsg3-depleted desmosomes in PV or Dsg1-depleted desmosomes in PF. Furthermore, PV-IgG activates an "outside-in" signaling pathway to induce disassembly of desmosomal components from the inside of the cells by phosphorylation of proteins, including Dsg3. On the other hand, Pemphigus-IgG-augmented signaling pathways may be linked to the secretion of cytokines such as in case of pemphigus herpetiformis and chemokines that initiate or activate inflammation. In this article, the classification of pemphigus and the characteristic pathomechanisms for acantholysis will be reviewed, with particular emphasis on the molecular and biochemical cell biology of these diseases.
Kitajima
Yasuo
Y
Department of Dermatology, Gifu University School of Medicine, Gifu City, Japan. yaskitaj@gifu-u.ac.jp
Aoyama
Yumi
Y
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D002448:Cell Adhesion; D051183:Desmoglein 1 / Q000276:immunology; D051184:Desmoglein 3 / Q000276:immunology; D003896:Desmosomes / Q000378:metabolism; D006801:Humans; D010392:Pemphigus / Q000145:classification / Q000209:etiology* / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D051183:Desmoglein 1; D051184:Desmoglein 3