Single-cell multi-omics analysis identifies two distinct phenotypes of newly-onset microscopic polyangiitis.

Autor: Nishide M; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. nishide@imed3.med.osaka-u.ac.jp.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan. nishide@imed3.med.osaka-u.ac.jp.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. nishide@imed3.med.osaka-u.ac.jp., Nishimura K; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Joint Research Chair of Innovative Drug Discovery in Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Research Division, Chugai Pharmaceutical Co. Ltd, Yokohama, Kanagawa, Japan., Matsushita H; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Joint Research Chair of Innovative Drug Discovery in Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Research Division, Chugai Pharmaceutical Co. Ltd, Yokohama, Kanagawa, Japan., Edahiro R; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Inukai S; Research Division, Chugai Pharmaceutical Co. Ltd, Yokohama, Kanagawa, Japan., Shimagami H; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Kawada S; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Kato Y; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Kawasaki T; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Tsujimoto K; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Kamon H; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Joint Research Chair of Innovative Drug Discovery in Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Research Division, Chugai Pharmaceutical Co. Ltd, Yokohama, Kanagawa, Japan., Omiya R; Joint Research Chair of Innovative Drug Discovery in Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Research Division, Chugai Pharmaceutical Co. Ltd, Yokohama, Kanagawa, Japan., Okada Y; Department of Statistical Genetics, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan.; Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Suita, Osaka, Japan.; Statistical Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Laboratory for Systems Genetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.; Department of Genome Informatics, Graduate School of Medicine, the University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan., Hattori K; Joint Research Chair of Innovative Drug Discovery in Immunology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Research Division, Chugai Pharmaceutical Co. Ltd, Yokohama, Kanagawa, Japan., Narazaki M; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan.; Department of Advanced Clinical and Translational Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan., Kumanogoh A; Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.; Department of Immunopathology, World Premier International Research Center Initiative (WPI), Immunology Frontier Research Center (IFReC), Osaka University, Suita, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.; Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives (OTRI), Osaka University, Suita, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.; Center for Infectious Diseases for Education and Research (CiDER), Osaka University, Suita, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.; Japan Agency for Medical Research and Development - Core Research for Evolutional Science and Technology (AMED-CREST), Osaka University, Suita, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.; Center for Advanced Modalities and DDS (CAMaD), Osaka University, Suita, Osaka, Japan. kumanogo@imed3.med.osaka-u.ac.jp.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 11; Vol. 14 (1), pp. 5789. Date of Electronic Publication: 2023 Oct 11.
DOI: 10.1038/s41467-023-41328-0
Abstrakt: The immunological basis of the clinical heterogeneity in autoimmune vasculitis remains poorly understood. In this study, we conduct single-cell transcriptome analyses on peripheral blood mononuclear cells (PBMCs) from newly-onset patients with microscopic polyangiitis (MPA). Increased proportions of activated CD14 + monocytes and CD14 + monocytes expressing interferon signature genes (ISGs) are distinctive features of MPA. Patient-specific analysis further classifies MPA into two groups. The MPA-MONO group is characterized by a high proportion of activated CD14 + monocytes, which persist before and after immunosuppressive therapy. These patients are clinically defined by increased monocyte ratio in the total PBMC count and have a high relapse rate. The MPA-IFN group is characterized by a high proportion of ISG + CD14 + monocytes. These patients are clinically defined by high serum interferon-alpha concentrations and show good response to immunosuppressive therapy. Our findings identify the immunological phenotypes of MPA and provide clinical insights for personalized treatment and accurate prognostic prediction.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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