Pemphigus vulgaris: recent advances in our understanding of its pathogenesis.
Pemphigus, a group of bullous diseases affecting the oral mucosa and the skin, is caused by antibody-mediated autoimmune reaction to desmogleins (Dsg), desmosomal transmembrane glycoproteins, leading to acantholysis. Pemphigus is classified into pemphigus vulgaris (PV), with suprabasal acantholysis, and pemphigus foliaceus (PF), with acantholysis in the more superficial epidermis. Pemphigus vulgaris is characterized by IgG autoantibodies against desmoglein 3 (Dsg 3), whereas the target of PF is Dsg1, although about 50% of PV patients also have Dsg1 autoantibodies. The clinical phenotype appears to be determined by the distribution of Dsg1 and Dsg3. PV patients with oral mucosal lesions have predominantly Dsg3 autoantibodies. Lesion distribution is related to the location of the antigen (Dgs 3 and/or Dgs 1) in the epithelium and specific autoantibody production. Coexpression of Dsg 1 and Dsg 3 in keratinocytes protects against blister formations in the presence of antibodies against only one of the two desmogleins. Recent molecular studies have shown that acantholysis can occur also in the presence of antibodies against 9 alpha nicotinic acetylcholine receptor (AChR). Cholinergic agonists can protect keratinocyte monolayers against anti-Dsg antibody-induced acantholysis and reverse acantholysis produced by PV IgGs.
Femiano
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Department of Odontostomatology, Orthodontics and Oral Surgery, Faculty of Medicine and Surgery, Second University of Naples, Naples, Italy.
D000051:Acantholysis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D000328:Adult; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D018678:Cholinergic Agents / Q000627:therapeutic use; D051183:Desmoglein 1 / Q000276:immunology; D051184:Desmoglein 3 / Q000276:immunology; D003896:Desmosomes / Q000276:immunology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015603:Keratinocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010392:Pemphigus / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D011978:Receptors, Nicotinic / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; C498540:CHRNA9 protein, human; D018678:Cholinergic Agents; C495297:DSG1 protein, human; C071894:DSG3 protein, human; D051183:Desmoglein 1; D051184:Desmoglein 3; D007074:Immunoglobulin G; D011978:Receptors, Nicotinic