title: Autoimmune reactivity against precursor form of desmoglein 1 in healthy Tunisians in the area of endemic pemphigus foliaceus.
abstract: BACKGROUND
  Desmoglein 1 (Dsg1), the pemphigus foliaceus (PF) antigen, is produced as a precursor (preDsg1) and is transported to the cell surface as the mature form (matDsg1). Recent studies show that B cells from North American individuals without pemphigus can potentially produce anti-preDsg1 IgG antibodies, but ELISA screening of large numbers of normal people in North America and Japan hardly ever shows circulating antibodies against preDsg1 or matDsg1. In contrast, in Tunisia, where PF is endemic, anti-Dsg1 IgGs are frequently detected in healthy individuals.
  
  
  OBJECTIVE
  To characterize these anti-Dsg1 antibodies from normal individuals in Tunisia.
  
  
  METHODS
  Sera from 16 healthy individuals and 9 PF patients in the endemic PF area in Tunisia, and sera from Japanese non-endemic PF patients were analyzed by immunoprecipitation-immunoblotting using recombinant proteins of preDsg1, matDsg1, and domain-swapped Dsg1/Dsg2 molecules.
  
  
  RESULTS
  Sera from normal Tunisian individuals reacted to preDsg1 alone (8/16) or more strongly to preDsg1 than to matDsg1 (7/16), while those from all Tunisian PF patients and Japanese non-endemic PF patients reacted similarly to preDsg1 and matDsg1, or preferentially to matDsg1. The epitopes recognized by anti-Dsg1 IgGs from normal Tunisian individuals were more frequently found in the C-terminal extracellular domains (EC3 to EC5), while those in Tunisian endemic PF patients were more widely distributed throughout the extracellular domains, suggesting IgGs against EC1 and EC2 developed during disease progression.
  
  
  CONCLUSIONS
  These findings indicate that IgG autoantibodies against Dsg1 are mostly raised against preDsg1 and/or C-terminal domains of Dsg1 in healthy Tunisians in the endemic area of PF.
authors.affiliation: Department of Immunology, Habib Bourguiba Hospital, Sfax, Tunisia.
authors.forename: Amina
authors.initials: A
authors.lastname: Toumi
authors.forename: Marwah Adly
authors.initials: MA
authors.lastname: Saleh
authors.forename: Jun
authors.initials: J
authors.lastname: Yamagami
authors.forename: Olfa
authors.initials: O
authors.lastname: Abida
authors.forename: Maryem
authors.initials: M
authors.lastname: Kallel
authors.forename: Abderrahmen
authors.initials: A
authors.lastname: Masmoudi
authors.forename: Sondes
authors.initials: S
authors.lastname: Makni
authors.forename: Hamida
authors.initials: H
authors.lastname: Turki
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hachiya
authors.forename: Keiko
authors.initials: K
authors.lastname: Kuroda
authors.forename: John R
authors.initials: JR
authors.lastname: Stanley
authors.forename: Hatem
authors.initials: H
authors.lastname: Masmoudi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
mesh_terms: D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D051183:Desmoglein 1 / Q000737:chemistry / Q000276:immunology*; D019353:Endemic Diseases / Q000706:statistics & numerical data*; D018604:Epitope Mapping; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D010392:Pemphigus / Q000453:epidemiology* / Q000276:immunology*; D017434:Protein Structure, Tertiary; D016036:Seroepidemiologic Studies; D014416:Tunisia / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; C495297:DSG1 protein, human; D051183:Desmoglein 1; D007074:Immunoglobulin G