title: Anti-desmoglein-1 antibodies in onchocerciasis, leishmaniasis and Chagas disease suggest a possible etiological link to Fogo selvagem.
abstract: Pemphigus foliaceus (PF) and the endemic form Fogo Selvagem (FS) are mediated by pathogenic antibodies to the EC1-2 domains of desmoglein-1. There is a preclinical phase with antibodies to only EC5. Based on geographic clustering of cases, FS is thought to have an, as yet unidentified, environmental trigger. In this study we have searched for anti-desmoglein-1 antibodies in sera from parasitic (leishmaniasis, Chagas, and onchocerciasis), and infectious diseases (leprosy and South American (SA) blastomycosis), which are prevalent in the same geographic regions of Brazil as FS. A specific and sensitive desmoglein-1 ELISA detected antibodies in 34 of 41 onchocerciasis (83%), 38 of 88 leishmaniasis (43%), 18 of 31 Chagas disease (58%), 7 of 28 SA blastomycosis (25%), and 14 of 83 leprosy sera (17%). These sera recognized epitopes restricted to the EC5 domain. These findings identify several etiological factors for FS. It is hypothesized that a component of insect vector saliva, rather than the parasite itself may trigger an antibody response to EC-5. In persons with the known HLA susceptibility alleles and living in endemic areas, a response to the EC1-2 domains may subsequently develop by epitope spreading with associated clinical signs of FS.
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, North Carolina, USA. ldiaz@med.unc.edu
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
authors.forename: Luis A
authors.initials: LA
authors.lastname: Arteaga
authors.forename: Julio
authors.initials: J
authors.lastname: Hilario-Vargas
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Simon
authors.initials: S
authors.lastname: Warren
authors.forename: Valeria
authors.initials: V
authors.lastname: Aoki
authors.forename: Gunter
authors.initials: G
authors.lastname: Hans-Filho
authors.forename: Donald
authors.initials: D
authors.lastname: Eaton
authors.forename: Vandir
authors.initials: V
authors.lastname: dos Santos
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nutman
authors.forename: Antonio Antunez
authors.initials: AA
authors.lastname: de Mayolo
authors.forename: Bahjat F
authors.initials: BF
authors.lastname: Qaqish
authors.forename: Sebastiao A P
authors.initials: SA
authors.lastname: Sampaio
authors.forename: Evandro A
authors.initials: EA
authors.lastname: Rivitti
mesh_terms: D000953:Antigens, Protozoan / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D015820:Cadherins / Q000737:chemistry / Q000276:immunology*; D014355:Chagas Disease / Q000453:epidemiology / Q000276:immunology*; D051183:Desmoglein 1; D019353:Endemic Diseases; D006801:Humans; D007299:Insect Bites and Stings / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D007896:Leishmaniasis / Q000453:epidemiology / Q000276:immunology*; D009855:Onchocerciasis / Q000453:epidemiology / Q000276:immunology*; D010392:Pemphigus / Q000453:epidemiology / Q000209:etiology / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016036:Seroepidemiologic Studies
chemical_list: D000953:Antigens, Protozoan; D001323:Autoantibodies; D015820:Cadherins; D051183:Desmoglein 1