Cutting Edge: Brazilian Pemphigus Foliaceus Anti-Desmoglein 1 Autoantibodies Cross-React with Sand Fly Salivary LJM11 Antigen

The environmental factors that contribute to the development of autoimmune diseases are largely unknown. Endemic pemphigus foliaceus in humans, known as Fogo Selvagem (FS) in Brazil, is mediated by pathogenic IgG4 autoantibodies against desmoglein1 (Dsg1). Clusters of FS overlap with those of leishmaniasis, a disease transmitted by sand fly (Lutzomyia longipalpis) bites. In this study we show that salivary antigens from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS antibodies. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 antibodies. Thus, insect bites may deliver salivary antigens that initiate a cross-reactive IgG4 antibody response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, non-infectious antigen and the development of potentially pathogenic autoantibodies in an autoimmune disease