From metabolomics to transfusion-associated immunomodulation

• Published in: Current opinion in immunology Vol. 96; p. 102646
• Main Authors: D’Alessandro, Angelo, Zimring, James C
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2025
• Subjects: Animals; Biomarkers; Blood Transfusion; Humans; Immunomodulation; Metabolomics - methods; Transfusion Reaction - immunology
• ISSN: 0952-7915; 1879-0372
• DOI: 10.1016/j.coi.2025.102646

This review summarizes recent advances in metabolomics that have enhanced our understanding of transfusion-related immunomodulation (TRIM), highlighting how biochemical changes in stored blood products — with a focus on packed red blood cells — affect recipient immune responses. Metabolomics has revealed critical biochemical shifts — termed storage lesions — in blood products, notably accumulation of oxidized lipids, extracellular vesicles, and hemolysis-derived molecules, such as free heme and iron. These metabolites influence recipient immunity by triggering both inflammatory and immunosuppressive pathways, mediated through mechanisms involving redox imbalance, inflammasome activation, and modulation of immune cell metabolism. Studies underscore that the immunological outcomes of transfusions are shaped not only by storage duration but also by donor-specific metabolic profiles influenced by genetics, diet, and environmental exposures. Metabolic profiling has identified novel biomarkers, such as hypoxanthine and kynurenine, which correlate with transfusion quality and immunological impact. Metabolomics has transformed our understanding of TRIM, emphasizing that transfusion is an active biochemical intervention rather than passive fluid replacement. Moving forward, integrating metabolomic insights into transfusion medicine promises personalized strategies — selecting blood units based on metabolic rather than chronological age and donor characteristics — thus improving safety and clinical outcomes in transfusion recipients.