Recent advances in the study of the pathophysiology of pemphigus

Recent rapid advances in the basic research into pemphigus have provided many insights into its pathophysiology. In particular, a recently developed enzyme-linked immunosorbent assay (ELISA) for desmogleins 1 and 3 (Dsg1 and Dsg3), antigens for pemphigus foliaceus (PF) and pemphigus vulgaris (PV), respectively, has led to great progress in the diagnosis and classification of pemphigus, as well as in understanding its pathomechanisms. Studies with the anti-Dsg1 and anti-Dsg3 antibodies have indicated that there are two types of PV, the mucosal dominant type and the mucocutaneous type. The same ELISA has identified the antigens in pemphigus herpetiformis. The autoantigens detected by this ELISA correlate well with the clinical features in pemphigus patients in showing the shift between PV and PF. In addition, the Dsg compensation theory proposed by Stanley and Amagai can reasonably explain the different depths of skin lesions and the different occurrences of skin and oral mucosal lesions between PV and PF. Furthermore, a complicated profile of autoantigens in paraneoplastic pemphigus (PNP) has been indicated in various biochemical studies, and IgG anti-Dsg1 and anti-Dsg3 antibodies have been detected in serum from all the PNP patients by the above ELISA. On the other hand, serum from subcorneal pustular dermatosis type IgA pemphigus patients have been shown to react with Dsc1, another type of desmosomal cadherin, by a novel cDNA transfection method. In addition, IgA anti-Dsg1 and anti-Dsg3 antibodies have been detected in a few patients with IgA pemphigus by an ELISA for IgA antibodies. Various autoimmune bullous diseases, including several types of pemphigus, are the only diseases in which the pathogenic role of circulating autoantibodies has been confirmed using the newborn mouse animal model. Therefore, studies of the pathophysiology of pemphigus are extremely important as a paradigm for research into various types of autoimmune diseases in other fields.