https://www.um.edu.mt/library/oar/handle/123456789/815 2026-10-10T19:11:02Z 2026-10-10T19:11:02Z Moore, Andrew R. Zheng, Hong Ganesan, Ananthakrishnan Hasin-Brumshtein, Yehudit Maddali, Manoj V. Levitt, Joseph E. van der Poll, Tom Lu, Jingyi Bouma, Hjalmar R. Scicluna, Brendon P. Giamarellos-Bourboulis, Evangelos J. Kotsaki, Antigone Martin-Loeches, Ignacio Garduno, Alexis Hinson, Jeremiah Rothman, Richard E. Sevransky, Jonathan Wright, David W. Atreya, Mihir R. Moldawer, Lyle L. Efron, Philip A. Kralovcova, Marcela Karvunidis, Thomas Giannini, Heather M. Meyer, Nuala J. Sweeney, Timothy E. Rogers, Angela J. Khatri, Purvesh https://www.um.edu.mt/library/oar/handle/123456789/149894 2026-10-09T13:53:30Z 2025-01-01T00:00:00Z

Title: A consensus immune dysregulation framework for sepsis and critical illnesses Authors: Moore, Andrew R.; Zheng, Hong; Ganesan, Ananthakrishnan; Hasin-Brumshtein, Yehudit; Maddali, Manoj V.; Levitt, Joseph E.; van der Poll, Tom; Lu, Jingyi; Bouma, Hjalmar R.; Scicluna, Brendon P.; Giamarellos-Bourboulis, Evangelos J.; Kotsaki, Antigone; Martin-Loeches, Ignacio; Garduno, Alexis; Hinson, Jeremiah; Rothman, Richard E.; Sevransky, Jonathan; Wright, David W.; Atreya, Mihir R.; Moldawer, Lyle L.; Efron, Philip A.; Kralovcova, Marcela; Karvunidis, Thomas; Giannini, Heather M.; Meyer, Nuala J.; Sweeney, Timothy E.; Rogers, Angela J.; Khatri, Purvesh Abstract: Critical care syndromes such as sepsis, acute respiratory distress syndrome (ARDS) and trauma continue to have unacceptably high morbidity and mortality, with progress limited by the inherent heterogeneity within syndromic illnesses. Although numerous immune endotypes have been proposed for sepsis and critical care, the similarities and differences between these endotypes remain unclear, hindering clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine in critical care through the sharing of transcriptomic data. Here, evaluating the overlap of existing immune endotypes in sepsis across >7,074 samples from 37 independent cohorts, we developed cell-type-specific gene expression signatures to quantify dysregulation within immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. Importantly, this dysregulation was also observed in patients with ARDS, trauma and burns, suggesting a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation are associated with differential mortality in patients treated with anakinra in the SAVE-MORE trial (n = 452) and corticosteroids in the VICTAS (n = 89) and VANISH (n = 117) trials, underscoring their prognostic and therapeutic implications. In conclusion, our proposed immunology-based framework for quantifying cellular compartment dysregulation offers a potentially valuable tool for understanding immune dysregulation in critical illness with prognostic and therapeutic significance.

2025-01-01T00:00:00Z Moore, Andrew R. Zheng, Hong Ganesan, Ananthakrishnan Hasin-Brumshtein, Yehudit Maddali, Manoj V. Levitt, Joseph E. van der Poll, Tom Lu, Jingyi Bouma, Hjalmar R. Scicluna, Brendon P. Giamarellos-Bourboulis, Evangelos J. Kotsaki, Antigone Martin-Loeches, Ignacio Garduno, Alexis Hinson, Jeremiah Rothman, Richard E. Sevransky, Jonathan Wright, David W. Atreya, Mihir R. Moldawer, Lyle L. Efron, Philip A. Kralovcova, Marcela Karvunidis, Thomas Giannini, Heather M. Meyer, Nuala J. Sweeney, Timothy E. Rogers, Angela J. Khatri, Purvesh https://www.um.edu.mt/library/oar/handle/123456789/149892 2026-10-09T13:43:32Z 2025-01-01T00:00:00Z

Title: Author correction : a consensus immune dysregulation framework for sepsis and critical illnesses Authors: Moore, Andrew R.; Zheng, Hong; Ganesan, Ananthakrishnan; Hasin-Brumshtein, Yehudit; Maddali, Manoj V.; Levitt, Joseph E.; van der Poll, Tom; Lu, Jingyi; Bouma, Hjalmar R.; Scicluna, Brendon P.; Giamarellos-Bourboulis, Evangelos J.; Kotsaki, Antigone; Martin-Loeches, Ignacio; Garduno, Alexis; Hinson, Jeremiah; Rothman, Richard E.; Sevransky, Jonathan; Wright, David W.; Atreya, Mihir R.; Moldawer, Lyle L.; Efron, Philip A.; Kralovcova, Marcela; Karvunidis, Thomas; Giannini, Heather M.; Meyer, Nuala J.; Sweeney, Timothy E.; Rogers, Angela J.; Khatri, Purvesh Abstract: Critical care syndromes such as sepsis, acute respiratory distress syndrome (ARDS), and trauma are characterized by high heterogeneity and mortality. Unsupervised transcriptomic analysis across multi-cohort datasets demonstrates that previously described sepsis immune endotypes converge into consensus molecular clusters driven by myeloid and lymphoid dysregulation. The Human Immune Dysregulation Evaluation Framework (Hi-DEF) quantifies immune dysfunction continuously along myeloid and lymphoid axes. Severe dysregulation in these compartments correlates with disease severity, 30-day mortality, and differential clinical responses to immunomodulatory therapies across diverse critical illness syndromes.

2025-01-01T00:00:00Z Chouchane, Osoul Michels, Erik H.A. Leite, Giuseppe G.F. de Vos, Alex F. de Brabander, Justin Butler, Joe M. Brands, Xanthe Haak, Bastiaan W. Klarenbeek, Augustijn M. Joost Wiersinga, W. Scicluna, Brendon P. van 't Veer, Cornelis Kaas, Kathrine F. Petrosius, Valdemaras Schoof, Erwin M. van der Poll, Tom https://www.um.edu.mt/library/oar/handle/123456789/149879 2026-10-09T05:54:24Z 2025-01-01T00:00:00Z

Title: The proteomic landscape of blood monocytes in community-acquired pneumonia Authors: Chouchane, Osoul; Michels, Erik H.A.; Leite, Giuseppe G.F.; de Vos, Alex F.; de Brabander, Justin; Butler, Joe M.; Brands, Xanthe; Haak, Bastiaan W.; Klarenbeek, Augustijn M.; Joost Wiersinga, W.; Scicluna, Brendon P.; van 't Veer, Cornelis; Kaas, Kathrine F.; Petrosius, Valdemaras; Schoof, Erwin M.; van der Poll, Tom Abstract: Introduction: Monocytes play a pivotal role in the regulation of inflammation and pathogen clearance during infection. Knowledge of the human monocyte proteome during infection is limited. We present a comprehensive proteome profile of blood monocytes from patients with community-acquired pneumonia (CAP), one of the most common infectious diseases, and controls without infection. Methods: Monocytes were purified from blood of patients with CAP within 16 h of admission to a general hospital ward and from controls matched for sex, age and comorbidities. Monocyte proteins were measured using liquid chromatography/mass spectrometry. The transcriptome was analysed in the same samples by RNA sequencing. Monocytes were stimulated with lipopolysaccharide for 24 h, after which cytokines were measured in the supernatant. Results: We analysed the monocyte proteome of 34 CAP patients and 23 controls. Out of 7315 annotated proteins, 1340 (18.3%) were differentially abundant between groups. Functional enrichment analyses revealed a marked downregulation of mitochondrial respiration processes in patient monocytes; pathways pertaining to cell cycle, cytokine signalling and cell death were upregulated in patient monocytes. Monocyte mRNA levels correlated poorly with the abundance of corresponding proteins and associated functional pathways, raising caution regarding interpretation of functionality estimates based on transcriptome analyses. Differential expression of monocyte proteins had functional and clinical implications as indicated by associations with cytokine production capacity, disease severity and time to clinical stability. Conclusion: This study provides a publicly available monocyte protein atlas that can serve as a resource for future research on monocyte functions during infection.

2025-01-01T00:00:00Z Guerra, Joel Jentho, Elisa Schäuble, Sascha Scicluna, Brendon P. Vivas, Wolfgang Martínez-Alarcón, Dania Groth, Marco King, Emma Röstel, Franziska Hirth, Gianna Soares, Miguel P. Wiech, Thorsten Panagiotou, Gianni Bauer, Michael Hoerr, Verena Weis, Sebastian https://www.um.edu.mt/library/oar/handle/123456789/149868 2026-10-08T13:26:16Z 2026-01-01T00:00:00Z

Title: Control of renal central carbon metabolism by heme oxygenase-1 Authors: Guerra, Joel; Jentho, Elisa; Schäuble, Sascha; Scicluna, Brendon P.; Vivas, Wolfgang; Martínez-Alarcón, Dania; Groth, Marco; King, Emma; Röstel, Franziska; Hirth, Gianna; Soares, Miguel P.; Wiech, Thorsten; Panagiotou, Gianni; Bauer, Michael; Hoerr, Verena; Weis, Sebastian Abstract: Metabolic adaptation is an integral part of the organismal stress-response. In this study, we investigate the role of Hmox1 in mediating metabolic adaptation under both physiological and hemolytic stress conditions. Using an inducible Hmox1 deletion model (Hmox1 R26Δ/Δ ), we demonstrate that Hmox1 expression is essential for preventing heme-induced kidney failure. Our integrative approach, combining bulk RNA sequencing and targeted metabolomics within silico metabolic modeling, revealed a compromised pentose phosphate pathway (PPP) in failed renal adaptation after Hmox1 deletion. This study underscores the critical role of Hmox1 for PPP regulation and sheds light on the metabolic pathways involved in kidney dysfunction due to hemolytic diseases.

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