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Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity.
Iwamura, Chiaki; Hirahara, Kiyoshi; Kiuchi, Masahiro; Ikehara, Sanae; Azuma, Kazuhiko; Shimada, Tadanaga; Kuriyama, Sachiko; Ohki, Syota; Yamamoto, Emiri; Inaba, Yosuke; Shiko, Yuki; Aoki, Ami; Kokubo, Kota; Hirasawa, Rui; Hishiya, Takahisa; Tsuji, Kaori; Nagaoka, Tetsutaro; Ishikawa, Satoru; Kojima, Akira; Mito, Haruki; Hase, Ryota; Kasahara, Yasunori; Kuriyama, Naohide; Tsukamoto, Tetsuya; Nakamura, Sukeyuki; Urushibara, Takashi; Kaneda, Satoru; Sakao, Seiichiro; Tobiume, Minoru; Suzuki, Yoshio; Tsujiwaki, Mitsuhiro; Kubo, Terufumi; Hasegawa, Tadashi; Nakase, Hiroshi; Nishida, Osamu; Takahashi, Kazuhisa; Baba, Komei; Iizumi, Yoko; Okazaki, Toshiya; Kimura, Motoko Y; Yoshino, Ichiro; Igari, Hidetoshi; Nakajima, Hiroshi; Suzuki, Takuji; Hanaoka, Hideki; Nakada, Taka-Aki; Ikehara, Yuzuru; Yokote, Koutaro; Nakayama, Toshinori.
Afiliación
  • Iwamura C; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Hirahara K; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Kiuchi M; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Ikehara S; Department of Pathology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Azuma K; Department of Pathology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Shimada T; Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Kuriyama S; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Ohki S; Department of Pathology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Yamamoto E; Department of Pathology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Inaba Y; Clinical Research Center, Chiba University Hospital, Chiba 260-8677, Japan.
  • Shiko Y; Clinical Research Center, Chiba University Hospital, Chiba 260-8677, Japan.
  • Aoki A; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Kokubo K; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Hirasawa R; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Hishiya T; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Tsuji K; Department of Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Nagaoka T; Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8431, Japan.
  • Ishikawa S; Department of Respiratory Medicine, Funabashi Central Hospital, Chiba 273-8556, Japan.
  • Kojima A; Department of Respiratory Medicine, Funabashi Central Hospital, Chiba 273-8556, Japan.
  • Mito H; Department of Infectious Diseases, Japanese Red Cross Narita Hospital, Chiba 286-0041, Japan.
  • Hase R; Department of Infectious Diseases, Japanese Red Cross Narita Hospital, Chiba 286-0041, Japan.
  • Kasahara Y; Department of Respiratory Medicine, Eastern Chiba Medical Center, Chiba 283-8686, Japan.
  • Kuriyama N; Department of Anesthesiology and Critical Care Medicine, School of Medicine, Fujita Health University, Aichi 470-1192, Japan.
  • Tsukamoto T; Department of Pathology, School of Medicine, Fujita Health University, Aichi 470-1192, Japan.
  • Nakamura S; Department of Respirology, Funabashi Municipal Medical CenterChiba 273-8588, Japan.
  • Urushibara T; Department of Respirology, Kimitsu Chuo Hospital, Chiba 292-0822, Japan.
  • Kaneda S; Department of Gastroenterology, National Hospital Organization Chiba Medical Center, Chiba 260-8606, Japan.
  • Sakao S; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Tobiume M; Department of Pathology, Asahi General Hospital, Chiba 289-2511, Japan.
  • Suzuki Y; Department of Pathology, Asahi General Hospital, Chiba 289-2511, Japan.
  • Tsujiwaki M; Department of Surgical Pathology, Sapporo Medical University of Medicine, Sapporo 060-8543, Japan.
  • Kubo T; Department of Surgical Pathology, Sapporo Medical University of Medicine, Sapporo 060-8543, Japan.
  • Hasegawa T; Department of Surgical Pathology, Sapporo Medical University of Medicine, Sapporo 060-8543, Japan.
  • Nakase H; Department of Gastroenterology and Hepatology, Sapporo Medical University of Medicine, Sapporo 060-8543, Japan.
  • Nishida O; Department of Anesthesiology and Critical Care Medicine, School of Medicine, Fujita Health University, Aichi 470-1192, Japan.
  • Takahashi K; Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8431, Japan.
  • Baba K; DLC Research Institute LLC, Nagasaki 850-0011, Japan.
  • Iizumi Y; CNT-Application Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8565, Japan.
  • Okazaki T; CNT-Application Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba 305-8565, Japan.
  • Kimura MY; Department of Experimental Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Yoshino I; Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Igari H; Department of Infectious Diseases, Chiba University Hospital, Chiba 260-8677, Japan.
  • Nakajima H; COVID-19 Vaccine Center, Chiba University Hospital, Chiba 260-8677, Japan.
  • Suzuki T; COVID-19 Vaccine Center, Chiba University Hospital, Chiba 260-8677, Japan.
  • Hanaoka H; Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Nakada TA; Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Ikehara Y; Clinical Research Center, Chiba University Hospital, Chiba 260-8677, Japan.
  • Yokote K; Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
  • Nakayama T; Department of Pathology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Proc Natl Acad Sci U S A ; 119(33): e2203437119, 2022 08 16.
Article en En | MEDLINE | ID: mdl-35895716
The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vasculitis / Índice de Severidad de la Enfermedad / Cadenas Ligeras de Miosina / SARS-CoV-2 / COVID-19 / Tromboinflamación / Pulmón Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A 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: Vasculitis / Índice de Severidad de la Enfermedad / Cadenas Ligeras de Miosina / SARS-CoV-2 / COVID-19 / Tromboinflamación / Pulmón Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos