AIMing for Survival: The Impact of the free and total AIM Concentration in Septic Patients

Birte Dyck¹Ulrich Bosch Dos Santos^2,3Corinna Müller²Hartmuth Nowak^1,4Tim Rahmel¹Lars Palmowski¹Matthias Unterberg¹Alexander Wolf¹Alexander von Busch¹Andrea Witowski¹Britta Westhus¹Barbara Sitek¹Katharina Rump¹Christian Putensen⁵Stefan Ehrentraut⁵Alexander Zarbock⁶Dietrich Henzler⁷Nina Babel⁸Martin Eisenacher^10,11,9Katrin Marcus^10,9Björn Ellger¹²Björn Koos¹Michael Adamzik¹Dominik Ziehe^1*Lars Bergmann¹

• ¹Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Bochum GmbH, Bochum, Germany
• ²Biotest AG, Dreieich, Germany
• ³AIMunity GmbH, Bremen, Germany
• ⁴Zentrum für Künstliche Intelligenz, Medizininformatik und Datenwissenschaften, Bochum, Germany, Bochum, Germany
• ⁵Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Bonn, Bonn, Germany
• ⁶Universitatsklinikum Munster Klinik fur Anasthesiologie Operative Intensivmedizin und Schmerztherapie, Münster, Germany
• ⁷Klinik für Anästhesiologie, operative Intensiv-, Rettungsmedizin und Schmerztherapie, Ruhr-Universität Bochum, Klinikum Herford, Herford, Germany
• ⁸Center for Translational Medicine, Medical Clinic I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany
• ⁹Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany; Center for Proteindiagnostics (PRODI), Bochum, Germany
• ¹⁰Medical Proteome Analysis, Ruhr University Bochum, Bochum, Germany
• ¹¹CUBiMed.RUB, Core Unit Bioinformatics, Medical Faculty, Ruhr University Bochum, Bochum, Germany
• ¹²Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Klinikum Westfalen, Dortmund, Germany

Background: Sepsis, 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. Methods: We 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®. Results: High 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). Conclusion: Total 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).