Macrophage expression and prognostic significance of the long pentraxin PTX3 in COVID-19

被引:118
作者
Brunetta, Enrico [1 ,2 ]
Folci, Marco [1 ,2 ]
Bottazzi, Barbara [1 ]
De Santis, Maria [1 ]
Gritti, Giuseppe [3 ]
Protti, Alessandro [1 ,2 ]
Mapelli, Sarah N. [1 ]
Bonovas, Stefanos [1 ,2 ]
Piovani, Daniele [1 ,2 ]
Leone, Roberto [1 ]
My, Ilaria [1 ,2 ]
Zanon, Veronica [1 ]
Spata, Gianmarco [1 ]
Bacci, Monica [1 ]
Supino, Domenico [2 ]
Carnevale, Silvia [2 ]
Sironi, Marina [1 ]
Davoudian, Sadaf [1 ]
Peano, Clelia [1 ,4 ]
Landi, Francesco [3 ]
Di Marco, Fabiano [5 ,6 ]
Raimondi, Federico [5 ]
Gianatti, Andrea [7 ]
Angelini, Claudio [1 ]
Rambaldi, Alessandro [3 ,8 ]
Garlanda, Cecilia [1 ,2 ]
Ciccarelli, Michele [1 ]
Cecconi, Maurizio [1 ,2 ]
Mantovani, Alberto [1 ,2 ,9 ]
机构
[1] Humanitas Clin & Res Ctr IRCCS, Milan, Italy
[2] Humanitas Univ, Dept Biomed Sci, Milan, Italy
[3] Azienda Osped Socio Sanit Terr Papa Giovanni XXII, Unit Hematol, Bergamo, Italy
[4] CNR, UoS Milan, Inst Genet & Biomed Res, Milan, Italy
[5] Azienda Osped Socio Sanit Terr Papa Giovanni XXII, Unit Pneumol, Bergamo, Italy
[6] Univ Milan, Dept Hlth Sci, Milan, Italy
[7] Azienda Osped Socio Sanit Terr Papa Giovanni XXII, Unit Pathol, Bergamo, Italy
[8] Univ Milan, Dept Oncol & Hematooncol, Milan, Italy
[9] Queen Mary Univ London, William Harvey Res Inst, London, England
基金
欧盟地平线“2020”; 欧洲研究理事会;
关键词
KAWASAKI-LIKE DISEASE; SHORT-TERM MORTALITY; INNATE IMMUNITY; INFECTION; INFLAMMATION; CORRELATE; SITES;
D O I
10.1038/s41590-020-00832-x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mantovani and colleagues report elevated circulating concentrations of the long pentraxin PTX3 in patients with severe COVID-19. Within this cohort, early detection of high PTX3 concentrations emerged as a strong predictor of decreased survival. Long pentraxin 3 (PTX3) is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation(1-3). The present study was designed to assess the presence and significance of PTX3 in Coronavirus Disease 2019 (COVID-19)(4-7). RNA-sequencing analysis of peripheral blood mononuclear cells, single-cell bioinformatics analysis and immunohistochemistry of lung autopsy samples revealed that myelomonocytic cells and endothelial cells express high levels of PTX3 in patients with COVID-19. Increased plasma concentrations of PTX3 were detected in 96 patients with COVID-19. PTX3 emerged as a strong independent predictor of 28-d mortality in multivariable analysis, better than conventional markers of inflammation, in hospitalized patients with COVID-19. The prognostic significance of PTX3 abundance for mortality was confirmed in a second independent cohort (54 patients). Thus, circulating and lung myelomonocytic cells and endothelial cells are a major source of PTX3, and PTX3 plasma concentration can serve as an independent strong prognostic indicator of short-term mortality in COVID-19.
引用
收藏
页码:19 / 24
页数:6
相关论文
共 63 条
[11]   Early Predictors of Clinical Deterioration in a Cohort of 239 Patients Hospitalized for Covid-19 Infection in Lombardy, Italy [J].
Cecconi, Maurizio ;
Piovani, Daniele ;
Brunetta, Enrico ;
Aghemo, Alessio ;
Greco, Massimiliano ;
Ciccarelli, Michele ;
Angelini, Claudio ;
Voza, Antonio ;
Omodei, Paolo ;
Vespa, Edoardo ;
Pugliese, Nicola ;
Parigi, Tommaso Lorenzo ;
Folci, Marco ;
Danese, Silvio ;
Bonovas, Stefanos .
JOURNAL OF CLINICAL MEDICINE, 2020, 9 (05)
[12]   Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China [J].
Chen, Ruchong ;
Sang, Ling ;
Jiang, Mei ;
Yang, Zhaowei ;
Jia, Nan ;
Fu, Wanyi ;
Xie, Jiaxing ;
Guan, Weijie ;
Liang, Wenhua ;
Ni, Zhengyi ;
Hu, Yu ;
Liu, Lei ;
Shan, Hong ;
Lei, Chunliang ;
Peng, Yixiang ;
Wei, Li ;
Liu, Yong ;
Hu, Yahua ;
Peng, Peng ;
Wang, Jianming ;
Liu, Jiyang ;
Chen, Zhong ;
Li, Gang ;
Zheng, Zhijian ;
Qiu, Shaoqin ;
Luo, Jie ;
Ye, Changjiang ;
Zhu, Shaoyong ;
Zheng, Jinping ;
Zhang, Nuofu ;
Li, Yimin ;
He, Jianxing ;
Li, Jing ;
Li, Shiyue ;
Zhong, Nanshan .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2020, 146 (01) :89-100
[13]   COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis [J].
Chua, Robert Lorenz ;
Lukassen, Soeren ;
Trump, Saskia ;
Hennig, Bianca P. ;
Wendisch, Daniel ;
Pott, Fabian ;
Debnath, Olivia ;
Thuermann, Loreen ;
Kurth, Florian ;
Voelker, Maria Theresa ;
Kazmierski, Julia ;
Timmermann, Bernd ;
Twardziok, Sven ;
Schneider, Stefan ;
Machleidt, Felix ;
Mueller-Redetzky, Holger ;
Maier, Melanie ;
Krannich, Alexander ;
Schmidt, Sein ;
Balzer, Felix ;
Liebig, Johannes ;
Loske, Jennifer ;
Suttorp, Norbert ;
Eils, Juergen ;
Ishaque, Naveed ;
Liebert, Uwe Gerd ;
von Kalle, Christof ;
Hocke, Andreas ;
Witzenrath, Martin ;
Goffinet, Christine ;
Drosten, Christian ;
Laudi, Sven ;
Lehmann, Irina ;
Conrad, Christian ;
Sander, Leif-Erik ;
Eils, Roland .
NATURE BIOTECHNOLOGY, 2020, 38 (08) :970-+
[14]   Genetic PTX3 Deficiency and Aspergillosis in Stem-Cell Transplantation [J].
Cunha, Cristina ;
Aversa, Franco ;
Lacerda, Joao F. ;
Busca, Alessandro ;
Kurzai, Oliver ;
Grube, Matthias ;
Loeffler, Juergen ;
Maertens, Johan A. ;
Bell, Alain S. ;
Inforzato, Antonio ;
Barbati, Elisa ;
Almeida, Bruno ;
Santos e Sousa, Pedro ;
Barbui, Anna ;
Potenza, Leonardo ;
Caira, Morena ;
Rodrigues, Fernando ;
Salvatori, Giovanni ;
Pagano, Livio ;
Luppi, Mario ;
Mantovani, Alberto ;
Velardi, Andrea ;
Romani, Luigina ;
Carvalho, Agostinho .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (05) :421-432
[15]   Regulation of leukocyte recruitment by the long pentraxin PTX3 [J].
Deban, Livija ;
Russo, Remo Castro ;
Sironi, Marina ;
Moalli, Federica ;
Scanziani, Margherita ;
Zambelli, Vanessa ;
Cuccovillo, Ivan ;
Bastone, Antonio ;
Gobbi, Marco ;
Valentino, Sonia ;
Doni, Andrea ;
Garlanda, Cecilia ;
Danese, Silvio ;
Salvatori, Giovanni ;
Sassano, Marica ;
Evangelista, Virgilio ;
Rossi, Barbara ;
Zenaro, Elena ;
Constantin, Gabriela ;
Laudanna, Carlo ;
Bottazzi, Barbara ;
Mantovani, Alberto .
NATURE IMMUNOLOGY, 2010, 11 (04) :328-U74
[16]   Binding of the Long Pentraxin PTX3 to Factor H: Interacting Domains and Function in the Regulation of Complement Activation [J].
Deban, Livija ;
Jarva, Hanna ;
Lehtinen, Markus J. ;
Bottazzi, Barbara ;
Bastone, Antonio ;
Doni, Andrea ;
Jokiranta, T. Sakari ;
Mantovani, Alberto ;
Meri, Seppo .
JOURNAL OF IMMUNOLOGY, 2008, 181 (12) :8433-8440
[17]   STAR: ultrafast universal RNA-seq aligner [J].
Dobin, Alexander ;
Davis, Carrie A. ;
Schlesinger, Felix ;
Drenkow, Jorg ;
Zaleski, Chris ;
Jha, Sonali ;
Batut, Philippe ;
Chaisson, Mark ;
Gingeras, Thomas R. .
BIOINFORMATICS, 2013, 29 (01) :15-21
[18]   Detection of viral SARS-CoV-2 genomes and histopathological changes in endomyocardial biopsies [J].
Escher, Felicitas ;
Pietsch, Heiko ;
Aleshcheva, Ganna ;
Bock, Thomas ;
Baumeier, Christian ;
Elsaesser, Albrecht ;
Wenzel, Philip ;
Hamm, Christian ;
Westenfeld, Ralph ;
Schultheiss, Maximilian ;
Gross, Ulrich ;
Morawietz, Lars ;
Schultheiss, Heinz-Peter .
ESC HEART FAILURE, 2020, 7 (05) :2440-2447
[19]   Covid-19-Navigating the Uncharted [J].
Fauci, Anthony S. ;
Lane, H. Clifford ;
Redfield, Robert R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 382 (13) :1268-1269
[20]  
Fazzini F, 2001, ARTHRITIS RHEUM, V44, P2841, DOI 10.1002/1529-0131(200112)44:12<2841::AID-ART472>3.0.CO