title: Non-infectious environmental antigens as a trigger for the initiation of an autoimmune skin disease.
abstract: Pemphigus represents a group of organ specific autoimmune blistering disorders of the skin mediated by pathogenic autoantibodies with well-defined antigenic targets. While most of these diseases are sporadic, endemic forms of disease do exist. The endemic form of pemphigus foliaceus (also known as fogo selvagem, FS) exhibits epidemiological features that suggest exposure to hematophagous insect bites are a possible precipitating factor of this autoimmune disease, and provides a unique opportunity to study how environmental factors contribute to autoimmune disease development. FS patients and healthy individuals from endemic regions show an autoreactive IgM response that starts in early childhood and becomes restricted to IgG4 autoantibodies in FS patients. In searching for triggering environmental antigens, we have found that IgG4 and IgE autoantibodies from FS patients cross-react with a salivary antigen from sand flies. The presence of these cross-reactive antibodies and antibody genetic analysis confirming that these antibodies evolve from the same naïve B cells provides compelling evidence that this non-infectious environmental antigen could be the initial target of the autoantibody response in FS. Consequently, FS serves as an ideal model to study the impact of environmental antigens in the development of autoimmune disease.
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: ye_qian@med.unc.edu.
authors.forename: Ye
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Donna A
authors.initials: DA
authors.lastname: Culton
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Jeong
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Trupiano
authors.affiliation: Vector Molecular Biology Section, LMVR, National Institute of Allergy and Infectious Diseases, NIH, Rockville, MD 20852, USA.
authors.forename: Jesus G
authors.initials: JG
authors.lastname: Valenzuela
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology; D003429:Cross Reactions; D019353:Endemic Diseases; D004781:Environmental Exposure; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007299:Insect Bites and Stings / Q000276:immunology*; D019476:Insect Proteins / Q000276:immunology; D010392:Pemphigus / Q000453:epidemiology / Q000276:immunology*; D011576:Psychodidae / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000473:pathology
chemical_list: D000941:Antigens; D001323:Autoantibodies; D007074:Immunoglobulin G; D019476:Insect Proteins
keywords: Autoantibodies; Environmental antigens; IgE; IgG4; Pemphigus foliaceus