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Anti-Double-Stranded DNA Antibodies Recognize DNA Presented on HLA Class II Molecules of Systemic Lupus Erythematosus Risk Alleles.
Tsuji, Hideaki; Ohmura, Koichiro; Jin, Hui; Naito, Ryota; Arase, Noriko; Kohyama, Masako; Suenaga, Tadahiro; Sakakibara, Shuhei; Kochi, Yuta; Okada, Yukinori; Yamamoto, Kazuhiko; Kikutani, Hitoshi; Morinobu, Akio; Mimori, Tsuneyo; Arase, Hisashi.
Afiliación
  • Tsuji H; Kyoto University, Kyoto, Japan; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan, and Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Ohmura K; Kyoto University, Kyoto, Japan (current address: Kobe City Medical Center General Hospital, Kobe, Japan), : Kyoto University, Kyoto, Japan.
  • Jin H; Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Naito R; Kyoto University, Kyoto, Japan; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan, and Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Arase N; Osaka University Graduate School of Medicine, Suita, Japan.
  • Kohyama M; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan, and Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Suenaga T; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan, and Research Institute for Microbial Diseases, Osaka University, Suita, Japan.
  • Sakakibara S; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Kochi Y; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan, and Tokyo Medical and Dental University, Tokyo, Japan.
  • Okada Y; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan; Osaka University Graduate School of Medicine, Suita, Japan and RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Yamamoto K; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Kikutani H; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.
  • Morinobu A; Kyoto University, Kyoto, Japan (current address: Kobe City Medical Center General Hospital, Kobe, Japan), : Kyoto University, Kyoto, Japan.
  • Mimori T; Kyoto University, Kyoto, Japan (current address: Kobe City Medical Center General Hospital, Kobe, Japan), : Kyoto University, Kyoto, Japan.
  • Arase H; World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan; Research Institute for Microbial Diseases, Osaka University, Suita, Japan, and Center for Infectious Disease Education and Research, Osaka University, Suita, Japan.
Arthritis Rheumatol ; 74(1): 105-111, 2022 01.
Article en En | MEDLINE | ID: mdl-34164946
OBJECTIVE: Specific HLA class II alleles are associated with susceptibility to systemic lupus erythematosus (SLE). The role of HLA class II molecules in SLE pathogenesis remains unclear, although anti-DNA antibodies are specific to SLE and correlate with disease activity. We previously demonstrated that misfolded proteins bound to HLA class II molecules are specific targets for the autoantibodies produced in autoimmune diseases. This study was undertaken to validate our hypothesis that DNA binds to HLA class II molecules in a manner similar to that of misfolded proteins and that DNA bound to HLA class II molecules is involved in SLE pathogenesis. METHODS: We analyzed the binding of DNA to HLA class II molecules, as well as the response of cells expressing anti-DNA B cell receptors (BCRs) to cells expressing the DNA/HLA class II complex. RESULTS: Efficient binding of DNA to HLA class II molecules was observed in risk alleles of SLE, such as HLA-DRB1*15:01. The efficiency of DNA binding to each HLA-DR allele was positively associated with the risk of SLE conferred by the HLA-DR allele. In addition, reporter cells carrying anti-DNA BCRs were activated by cells expressing DNA/HLA class II complexes. CONCLUSION: These results provide evidence that DNA bound to HLA class II molecules is involved in SLE pathogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Antígenos de Histocompatibilidad Clase II / Anticuerpos Antinucleares / Lupus Eritematoso Sistémico Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Arthritis Rheumatol Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: ADN / Antígenos de Histocompatibilidad Clase II / Anticuerpos Antinucleares / Lupus Eritematoso Sistémico Tipo de estudio: Etiology_studies Límite: Humans Idioma: En Revista: Arthritis Rheumatol Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos