Desmoglein story from Masayuki Amagai teach us how to discover the beauty of nature.

After so many years of learning about the epidemiology, nature, diagnosis and management of the pemphigus group and other bullous dermatoses at University Department of Dermatology and Venereology, Zagreb University Hospital Center and School of Medicine, it was wonderful to discover – from the oral presentation entitled “Bullöse Dermatosen 2007” held by Prof. Michael Hertl in Graz (Austria) at the 3rd Derm Akademie Graz, October 20, 2007 – the beauty of the exact molecular mechanism of the pathogenesis of pemphigus and cell-cell adhesion of keratinocytes, clarifying the question of desmoglein as a transmembrane glycoprotein of the desmosome. The modern history of pemphigus began with the discovery of circulating antibodies against the cell surface of keratinocytes in the sera of patients with pemphigus vulgaris (PV) by Beutner and Jordan in 1964 (1,2). In the late 1970s and early 1980s, it was demonstrated that autoantibodies in pemphigus are pathogenic and induce blister formation in skin organ culture systems, and Anhalt demonstrated IgG passive transfer from patients to neonatal mice (3). In 1982, Stanley et al. identified PV antigen in PV sera as glycosylated 130kDa glycoprotein (4); later Hashimoto et al. showed epidermal extracts binding to 130-kDa polypeptide (5); and in 1984 Stanley et al. first characterized pemphigus foliaceus (PF) antigen as a polypeptide of about 160kDa and recognized by PF sera as identical to desmoglein 1 (Dsg (1). In 1991, Amagai et al. isolated a cDNA clone for the PV antigen from the sera of patients with PV (6). Both Dsg1 and PV antigen are cadherin-type adhesion molecules that occur in desmosomes. PV antigen is termed desmoglein 3 (Dsg3) closely related to Dsg1 (1). IgG autoantibodies against Dsg1 and Dsg3 are pathogenic and induce blister formation in pemphigus, and can cause suprabasilar acantholysis, a typical histologic finding in PV. Thus, pemphigus has been redefined as an antidesmoglein autoimmune disease. Acta Dermatovenerol Croat 2007;15(4):274 -275 NEWS AND COMMENTS