Precision Immunotherapy to Improve Sepsis Outcomes

作者：Evangelos J. Giamarellos‐Bourboulis, Antigone Kotsaki, Ioanna Kotsamidi, Aikaterini Efthymiou, Vasiliki Koutsoukou, Johannes Ehler, Alexandra Paridou, Frantzeska Frantzeskaki, Marcella C.A. Müller, Peter Pickkers, Sylvain Meylan, Ioannis Nikolopoulos, Mihaela Lupșe, Alexandra Gavala, Glykeria Vlachogianni, Nicky Solomonidi, Antonia Alevizou, Εumorfia Kondili, Eleni Antoniadou, Μαρία Νάκου, Νικόλαος Μάρκου, Erifili Hatziagelaki, Athanassios Prekates, Apostolos Komnos, Lieke Bakkerus, Marleen A. Slim, George Ν. Dalekos, A. Karapanagiotou, Sofia Ira Ktena, Gennaro De Pascale, V. Koulouras, Christos Psarrakis, Eleni Massa, Konstantina Dakou, Chrisoula Pazvanti, Aikaterini Ioakeimidou, Iraklis Tsangaris, Nikolaos Antonakos, Alexander P. J. Vlaar, Souzana Anisoglou, Thierry Calandra, Vasilios Papaioannou, Pavlos Myrianthefs, Maria Patrani, Ioannis Alamanos, Massimo Antonelli, Jos W. M. van der Meer, Tom van der Poll, W. Joost Wiersinga, Maria Ntaganou, Eleni Gkeka, Michael Bauer, Eleni Mouloudi, Mihai G. Netea, ImmunoSep Study Group, Artemis Bogosian, Vasiliki Bourika, Athanasia Chatzianastasiou, Effrosyni Dimopoulou, George Dimοpoulos, Leda Efstratiou, Eleni Florou, Eleni Ioanna Katsigianni, Paraskevi Kanellakopoulou, Myrto Kollia, Elli Konstantinou, Panagiotis Koufargyris, Miltiades Kyprianou, Styliani Micha, Onisiphoros Neophytou, Melina Nikolakea, Elisavet Olntasi, Dimitra Papatheodosiou, Varvara Perraki, Christina Maria Rimpa, Christina Sideratou, Chrysanthi Sidiropoulou, Emmanouel Sofianopoulos, Emmanouil Stylianakis, Georgios Tavoulareas, Ioannis Theodorou, Antonios Papadopoulos, Amalia Bolanou, Georgia Damoraki, Theologia Gkavogianni, Konstantina Katrini, Konstantinos Leventogiannis, Asimina Safarika, Athanasios Siampanos, Sokratis Katopodis, A Armaganidis, Eleni Karakike, Evdoxia Kyriazopoulou, Michail Rizos, Nikolaos Gatselis, Sara Georgiadou, Georgios Giannoulis, Vasiliki Lygoura, Georgios Perifanos, Anna Samakidou, Aggelos Stefos, Dafni Sveroni, Georgios Vatidis, Petros Boukas, Konstantinos Mantis, Dimitra Markopoulou, Eleni Papadaki, Eirini Demertzi, Konstantina Dimou, Eirini Ioannou, Dimitrios Kantas, Nikolaos Lagos, Γεώργιος Παπαθανάκος, Αθανάσιος Παπαθανασίου, Maria Paschali, Sofia Peristeri, M. Saranti, Nikoletta Stefanatou, Maria Vagia, Konstantin Nikolaou, Vassiliki Theodorou, Elli Antypa, E Chassou, Kosmas Kosmidis, Violetta Mourouzidou, Evangelia Panagiotidou, Achillefs Pitsoulis, Polychronis Tassioudis, Maria Vasileiou, Eleni Aimoniotou-Georgiou, Eirini Apostolidou, Apostolos Bakas, Eirini Fylaki, E. Papandreou, Μαρία Παπαθανασίου, Konstantinos Psaroulis, Zoi Aidoni, Pinelopi Amoiridou, Vasiliki Birmpa, Marios Karvouniaris, Konstantinos Pagioulas, Stella-Niki Primikyri, Ioanna Soultati, Alexandros Tsakalidis, Stella Tsianta, Christos Tsiantas, Iliana Tryfonidou, Nopi Veliki, Foteini Veroniki, Ioannis Alevroudis, Triantafyllenia Bargiota, Zoi Bosmou, Ioannis Kafantaris, Damianos Karapiperidis, Evangelia Michailidou, Chrysanthi Nakou, Savvas Papadopoulos, Maria Passakiotou, S. Patsatzakis, Panagiotis Roumelis, Styliani Soundoulounaki, Dafni Stamou, Christos Charatsis, Panagiotis Chaloulis, Periklis Faneromenos, Alessandro De Fanti, Fotis Gerosimou, Dimitris Kokaridas, Eirini Papageorgiou, Dimitris Rimarev, Konstantina Vryza, Konstantinos Athanasiou, Konstantinos Chatzigeorgiou, Varvara Grammatikopoulou, Athanasios Gravos, Sofia Kanakaki, Konstantina Katsifa, Evangelia Sklavou, Charilaos Tsapas, Paraskevi Tselioti, Periklis Katsiafylloudis, Dimitrios Papadopoulos, Asimina Valsamaki, Maria Xanthoudaki, Paraskevi Alexandropoulou, Ioannis Koutsodimitropoulos, Konstantinos Ouranos, Aikaterini Panagiotakopoulou, Eleni Stefanatou, Sofia Avgeri, Lampros Balaskas, Ourania Belagia, E. Bourgani, Aikaterini Flevari, Styliani Giannakaki, Georgia Katsagani, Theodora Katsarou, Clementine Bostantzoglou, Olga Kouniaki, Eleni Koutsougianni, D Markantonaki, Evgenia Nanou, Maria Poulou, Κωνσταντίνα Σταθοπούλου, Panagiotis Vasileiou, Efstratia Vrettou, K. Dimitroulakis, Dimitrios Karapiperis, Ioannis Katsiadramis, Anna Vemvetsou, Ioannis Giagtzoglou, Yorgos Nikolaidis, Christos Papadas, Panagiotis Patsaouras, Theoni Agapitou, Nikolaos Garmpis, Anastasia Kosmidou, Vasiliki Nanou, P. Nikolopoulos, Sofia Pouriki, Asimina Rautopoulou, Giannoula Tsekoura, Georgios Kassianidis, Giorgos Marinakis, Sofia Kokkini, Eleftherios Papadakis, Georgios Prinianakis, Αthanasia Proklou, Anna Korompeli, Panagiota Makrygianni, Evdoxia Tsigkou, Sebastian Weis, Frank Bloos, Petra Bloos, Martin Bräuer, Karen Dlubatz, Tobias Fischer, Anja Haucke, Carsten Herzog, Michael Hofmann, Karina Knuhr-Kohlberg, Andreas Kortgen, Carolin Neumann, Franziska Röstel, Hendrik Rüddel, Katrin Schwope, Anna Seidel, Mark Simon, Helga Skupin, Oliver Sommerfeld, Daniel Thomas‐Rüddel, Isabella Westermann, Johannes Winning, Mirjam Dijkstra, Maurice Kroon, Rombout Van Amstel, Niels van Mourik, Lonneke van Vught, Aline de Nooijer, Konstantin Föhse, Jacobien J. Hoogerwerf, Matthijs Kox, Jaap ten Oever, Mirela Flonta, Lucia Herbel, Zsuzsa Kalmár, Monica Muntean, Jean‐Daniel Chiche, Isabelle Cristiani, Gilda Filipe De Castro Rebelo, Aurélie Fayet, Clémence Ferlay, Charly Gilbert, Anouk Grandjean, Didier Le Roy, Alessia Marino, Marion Ohl, Thierry Roger, Tiia Snäkä, I. Sommer, Monica Vieira Da Silva, Aline Voidey, A. Caroli, Salvatore Lucio Cutuli, Valentina Di Gravio, Chiara Iacovelli, Marilena La Sorda, Gianmarco Lombardi, Luca Montini, Eloisa Sofia Tanzarella · 发表于：JAMA · 年份：2025 · DOI：10.1001/jama.2025.24175 · 被引用次数：52 · 研究领域：Sepsis Diagnosis and Treatment、Inflammation biomarkers and pathways、Neonatal and Maternal Infections

Importance: Sepsis is heterogeneous, and the optimal strategy for tailoring immunotherapy is uncertain. Objective: To investigate whether precision immunotherapy guided by the presence of macrophage activation-like syndrome or sepsis-induced immunoparalysis improves organ dysfunction by day 9. Design, Setting, and Participants: A randomized, double-blind, double-dummy, placebo-controlled clinical trial conducted in 6 countries. Patients with sepsis, defined by Sepsis-3, were included if they had community-acquired or hospital-acquired pneumonia or ventilator-associated pneumonia or bacteremia and sepsis and had displayed either macrophage activation-like syndrome (blood ferritin >4420 ng/mL) or sepsis-induced immunoparalysis (blood ferritin ≤4420 ng/mL and <5000 human leukocyte antigen DR receptors on CD45/CD14 monocytes). The first patient was enrolled August 5, 2021, and the last follow-up, April 29, 2024. Interventions: Eligible patients were randomized to receive standard care and precision immunotherapy or standard care and placebo. Those in the precision immunotherapy group with macrophage activation-like syndrome received anakinra intravenously (IV) and placebo subcutaneously, and those with sepsis-induced immunoparalysis received subcutaneous recombinant human interferon gamma and IV placebo. Those in the placebo group received both IV and subcutaneous placebo. Treatment was administered for up to 15 days. Main Outcomes and Measures: The primary end point was a decrea...