title: Overlapping IgG4 Responses to Self- and Environmental Antigens in Endemic Pemphigus Foliaceus.
abstract: The etiology of human autoimmune diseases in general remains largely unknown, although the genetic and environmental interplay may be relevant. This applies to the autoimmune diseases of the skin such as the pemphigus phenotypes and others. In this group, there is an endemic form of pemphigus foliaceus (also known as fogo selvagem [FS]) in which the pathogenic IgG4 autoantibody response to the self-antigen desmoglein 1 (Dsg1) cross-reacts with the LJM11 sand fly salivary gland Ag. In this investigation, we dissected the IgG4 autoantibody repertoires used by FS patients in response to endogenous self-Dsg1 and exogenous LJM11 sand fly Ag. Based on analyses of the genetic clonal signatures of these Abs, our results indicate that there is a significant overlap between these two responses, as all identified IgG4 mAbs cross-react to both Dsg1 and LJM11 Ags. Germline H- and L-chain V gene Abs generated according to mutated cross-reactive mAbs preserved their reactivity to both Ags. Our findings suggest that both Dsg1 autoantigen and LJM11 environmental Ag could be the initial antigenic stimulants for the IgG4 autoimmune responses in FS. These results support our hypothesis that LJM11 Ag plays a substantial role in triggering the IgG4 autoantibody development in FS and provide new insights on how noninfectious environmental Ag(s) may drive the generation of autoantibodies in IgG4-related autoimmune diseases.
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; 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;
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Jeong
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894;
authors.forename: Jian
authors.initials: J
authors.lastname: Ye
authors.affiliation: Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
authors.forename: Bim
authors.initials: B
authors.lastname: Dang
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
authors.forename: Maha
authors.identifier: http://orcid.org/0000-0002-8761-2215
authors.initials: M
authors.lastname: Abdeladhim
authors.affiliation: Departamento de Dermatologia, Universidade de Sao Paulo, Sao Paulo 04038, Brazil; and.
authors.forename: Valeria
authors.initials: V
authors.lastname: Aoki
authors.affiliation: Departamento de Dermatologia, Universidade Federal de Mato Grosso do Sul, Mato Grosso do Sul 79070, Brazil.
authors.forename: Gunter
authors.initials: G
authors.lastname: Hans-Filhio
authors.affiliation: Departamento de Dermatologia, Universidade de Sao Paulo, Sao Paulo 04038, Brazil; and.
authors.forename: Evandro A
authors.initials: EA
authors.lastname: Rivitti
authors.affiliation: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
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;
authors.forename: Luis A
authors.initials: LA
authors.lastname: Diaz
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D003429:Cross Reactions; D051183:Desmoglein 1 / Q000276:immunology; D019353:Endemic Diseases; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D019476:Insect Proteins / Q000276:immunology*; D010392:Pemphigus / Q000276:immunology*; D011576:Psychodidae / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; C495297:DSG1 protein, human; D051183:Desmoglein 1; D007074:Immunoglobulin G; D019476:Insect Proteins
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