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Autoantibodies to DSC3 in Pemphigus Exclusively Recognize Calcium-Dependent Epitope in Extracellular Domain 2.
Koga, Hiroshi; Teye, Kwesi; Otsuji, Yoshihiko; Ishii, Norito; Hashimoto, Takashi; Nakama, Takekuni.
Afiliación
  • Koga H; Department of Dermatology, School of Medicine, Kurume University, Kurume, Japan. Electronic address: hiroshi_koga@med.kurume-u.ac.jp.
  • Teye K; Institute of Cutaneous Cell Biology, Kurume University, Kurume, Japan.
  • Otsuji Y; Department of Dermatology, School of Medicine, Kurume University, Kurume, Japan.
  • Ishii N; Department of Dermatology, School of Medicine, Kurume University, Kurume, Japan.
  • Hashimoto T; Department of Dermatology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
  • Nakama T; Department of Dermatology, School of Medicine, Kurume University, Kurume, Japan.
J Invest Dermatol ; 141(9): 2123-2131.e2, 2021 09.
Article en En | MEDLINE | ID: mdl-33766509
Pemphigus is a group of autoimmune bullous diseases characterized by the presence of autoantibodies against adhesion molecules, desmogleins, and desmocollins (DSCs). The pathogenicity of anti-DSC3 antibodies in pemphigus has been demonstrated; however, its characteristics have not yet been elucidated. We aimed to analyze the characteristics of anti-DSC3 antibodies using DSC3 domain‒swapped desmoglein 2 molecules in which the prosequence and five extracellular (EC) domains of desmoglein 2 were replaced with the corresponding domains of human DSC3. Using these proteins, we established an ELISA and analyzed sera from 56 patients with pemphigus. In 34 pemphigus sera positive for DSC3 full-EC domains, 15 sera (44.1%) were positive for EC2 domain, whereas other domains were rarely positive. We assessed the reactivity to a calcium-dependent epitope in DSC3 by ELISA with EDTA. The reactivity with the EC2 domain was mostly compromised in the presence of EDTA. In the in vitro assay, IgG from patients with paraneoplastic pemphigus preadsorbed with EC2 prevented both reduction of DSC3 and keratinocyte dissociation as compared with that with EDTA-treated EC2. This study revealed a predominant recognition of calcium-dependent epitopes in EC2 domain by anti-DSC3 antibodies and its pathogenicity on keratinocyte adhesion through DSC3 depletion.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Queratinocitos / Epítopos Inmunodominantes / Pénfigo / Desmocolinas Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Queratinocitos / Epítopos Inmunodominantes / Pénfigo / Desmocolinas Límite: Humans Idioma: En Revista: J Invest Dermatol Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos