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 desmoglein 1 (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 Ags from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS Abs. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 Abs. Thus, insect bites may deliver salivary Ags that initiate a cross-reactive IgG4 Ab response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, noninfectious Ag and the development of potentially pathogenic autoantibodies in an autoimmune disease.
Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Ye
Y
Qian
Joseph S
JS
Jeong
Mike
M
Maldonado
Jesus G
JG
Valenzuela
Regis
R
Gomes
Clarissa
C
Teixeira
Flor
F
Evangelista
Bahjat
B
Qaqish
Valeria
V
Aoki
Gunter
G
Hans
Evandro A
EA
Rivitti
Donald
D
Eaton
Luis A
LA
Diaz
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001938:Brazil; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D047468:Immunoprecipitation; D007299:Insect Bites and Stings / Q000150:complications* / Q000453:epidemiology / Q000276:immunology; D051379:Mice; D010392:Pemphigus / Q000276:immunology*; D011576:Psychodidae / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens