AUTHOR=Dyck Birte , Bosch dos Santos Ulrich , Müller Corinna , Nowak Hartmuth , Rahmel Tim , Palmowski Lars , Unterberg Matthias , Wolf Alexander , von Busch Alexander , Witowski Andrea , Westhus Britta , Sitek Barbara , Rump Katharina , Putensen Christian , Ehrentraut Stefan Felix , Zarbock Alexander , Henzler Dietrich , Babel Nina , Eisenacher Martin , Marcus Katrin , Ellger Björn , Koos Björn , Adamzik Michael , Ziehe Dominik , Bergmann Lars TITLE=AIMing for survival: The impact of the free and total AIM concentration in septic patients JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1685119 DOI=10.3389/fimmu.2025.1685119 ISSN=1664-3224 ABSTRACT=BackgroundSepsis, a life-threatening condition caused by a dysregulated host response to infection, remains a major cause of mortality worldwide. Identifying reliable biomarkers for prognosis and treatment is urgently needed. This study investigates the role of the Apoptosis Inhibitor of Macrophages (AIM), also known as CD5L, as a potential prognostic biomarker and therapeutic target in sepsis.MethodsWe measured free and total AIM concentrations in 90 septic patients enrolled in SepsisDataNet.NRW cohort (German Clinical Trial Registry No. DRKS00018871; http://www.sepsisdatanet.nrw). Blood samples were collected on days 1, 4, and 8, and AIM levels were quantified using ELISA. Kaplan-Meier analysis and Cox regression were performed to assess the association between AIM levels and 30-day survival. Western blot analysis was performed to detect AIM in human serum IgM and in the IgM-enriched intravenous immunoglobulin IVIG preparation Pentaglobin®.ResultsHigh total AIM concentrations (>85 ng/ml) were significantly associated with improved 30-day survival on day 1 (HR: 3.131, 95% CI: 1.629-6.019, p = 0.009), 4 (HR: 2.525, 95% CI: 1.198-5.322, p = 0.0042), and day 8 (HR: 2.317, 95% CI: 0.8565-6.266, p = 0.0457). Free AIM showed a significant association with survival only on day 8 (HR: 2.374, 95% CI: 0.8721-6.461, p = 0.0393).ConclusionTotal AIM concentration is a significant predictor of a 30-day survival in sepsis, supporting its potential use as a prognostic biomarker. Our findings also suggest that AIM may serve as a valuable prognostic biomarker and a potential target for immune-modulating therapies, including IgM-enriched intravenous immunoglobulins (IVIGs).