AG Immunomonitoring

Sepsis and polytrauma - entities with a high prevalence and lethality - are accompanied by a systemic inflammatory response triggered by so-called damage- and pathogen-associated molecular patterns (DAMPs and PAMPs). Here, the "first cellular line of defence" of the innate immune system, the neutrophil granulocytes, are activated excessively. This often leads to immune dysfunction and subsequently multiorgan failure, which further increases the lethality of patients with sepsis and polytrauma. We would like to introduce you to our main research areas in the following.

The spectrum of methods for researching immune dysfunction is based on classical laboratory methods with a focus on cell physiological examinations, for example flow cytometry and other common immunological methods. Within our main focus we try to record changes in the immune status or the inflammatory response within systemic inflammation, such as in patients with sepsis or after severe injuries, precisely, reliably and in a patient-friendly manner. The focus hereby relies on the innate immune response and in particular the interaction of the cellular phase (neutrophil granulocytes) and the fluid phase (complement system). In addition, the cell physiological, phenotypic and functional parameters provide information on the interaction between neutrophil granulocytes and platelets, the so-called platelet-neutrophil complexes. For the modulation of immune cells and platelets, detailed pharmacological characterisations are performed in vitro, ex vivo and in clinical patient studies.

Translational and clinically relevant research: From the clinical problem - to the laboratory bench - back to the patient. According to this principle, clinical-scientific knowledge gaps are identified, experimentally processed and retranslated. This process is implemented through a variety of complex and validated models. In vitro, for example, a high-throughput screening was developed to investigate pharmacological interventions on immune cells and platelets in parallel. Furthermore, the method spectrum includes the development of an animal-free alternative for simulating the complex inflammatory response in human whole blood (ex vivo whole blood model), as well as clinical studies on material from patients with major surgery and extracorporeal circulation, after polytrauma and during sepsis.

The Immunomonitoring working group is actively involved in promoting young scientists. This takes place mainly within the framework of supervised disertations in the fields of medicine, molecular medicine, biochemistry and biology, biotechnology and others. The success of our students is reflected, for example, in first and co-authorships in publications, awards, as well as active participation in congresses.

1. Wohlgemuth L.*, Stratmann A.E.P.*, Münnich F., Bernhard S., Thomaß B.D., Münnich F., Mohamed A.O.K., Mannes M., Schmidt C.Q., Nilsson Ekdahl K., Nilsson B., Fauler M., Föhr K.J., Huber-Lang M., Messerer D.A.C.,2022. Modulation of Neutrophil Activity by Soluble Complement Cleavage Products-An In-Depth Analysis. Cells. https://doi.org/10.3390/cells11203297

2. Stratmann, A.E.P.*,Wohlgemuth, L.*, Erber M. E., Bernhard S., Hug S., Fauler M., Vidoni L., Mohamed A.O.K., Thomaß B.D., Münnich F., Stukan L., Föhr K.J., Mannes M., Huber-Lang M.S., Messerer D.A.C., 2021. Simultaneous Measurement of Changes in Neutrophil Granulocyte Membrane Potential, Intracellular pH, and Cell Size by Multiparametric Flow Cytometry. Biomedicines. https://doi.org/10.3390/biomedicines9111504

3. Hug S., Bernhard S., Stratmann A.E.P, Erber M., Wohlgemuth L., Knapp C.L., Bauer J.M., Vidoni L., Fauler M., Föhr K.J., Radermacher P., Hoffmann A., Huber-Lang M., Messerer D.A.C.,2021. Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis. Front Immunol. https://doi.org/10.3389/fimmu.2021.642867

4. Bernhard S., Hug S., Stratmann A.E.P., Erber M., Vidoni L., Knapp C.L., Thomaß B.D., Fauler M., Nilsson B., Nilsson Ekdahl K., Föhr K., Braun C.K., Wohlgemuth L., Huber-Lang M., Messerer D.A.C., 2021. Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions. J Innate Immun. https://doi.org/10.1159/000514885

Further publications:

• Lisa Wohlgemuth

The working group was founded in the course of the Clinical Scientist Programme by PD Dr. David Messerer in 2019, who is now the head of the Department of Molecular Diagnostics at the Institute of Clinical Transfusion Medicine and Immunogenetics Ulm. Since 2023, the Immunomonitoring working group is led by M. Sc. Lisa Wohlgemuth. In the following, you will find the theses that were conducted in our research group.

Supervision M.Sc. Lisa Wohlgemuth / Prof. Dr. Markus Huber-Lang:

• Timo Westermann, Medical Dissertation, Focus on immunophenotypic analysis of neutrophil granulocytes in patients with DAMP- or PAMP-driven systemic inflammation
• Julia Altvater, Master Thesis, Focus on validation of the pharmacological influence of EMA/FDA approved drugs on neutrophil granulocytes in patients with systemic inflammation
• Hanna Bessler, Medical Dissertation, Focus on immunological changes as an early warning system for Sepsis-Induced Acute Kidney failure (SAKI)

Supervision PD Dr. David Messerer

• Pascal Lessing, Medical Dissertation, Focus on functional changes of neutrophil granulocytes in patients during major cardiac surgery
• Dominik Hüsken, Medical Dissertation, Focus on testing flow cytometry-based immunomonitoring in patients undergoing major cardiac surgery
• Alexander Koller, Medical Dissertation, Focus on drug repurposing in sepsis
• Paul Müller, Medical Dissertation, Focus on immune dysfunction in sepsis
• Bertram Thomaß, Medical Dissertation, Focus on analysis of large datasets of immune cells during sepsis and polytrauma
• Simon Lauer, Medical Dissertation, Focus on immune dysfunction in polytrauma
• Laura Stukan, Medical Dissertation, Focus on thromboinflammation in sepsis
• Frederik Münnich, Medical Dissertation, Focus on immune dysfunction in sepsis
• Larissa Höpfer, Medical Dissertation, Focus on neutrophil granulocyte dysfunction in cystic fibrosis
• Adam Mohamed, Medical Dissertation, Focus on ex-vivo modelling of polytrauma
• Christiane Knapp, Medical Dissertation, Focus on the role of platelet activating factor (PAF) in thromboinflammatory activity of neutrophil granulocytes
• Alexander Stratmann, Medical Dissertation, Focus on C5a-induced neutrophil granulocyte dysfunction

Alumni

• Andrea Tuchan, Master Thesis, "Drug repurposing in sepsis"
• Finn Münnich, Mathematics research assistant
• Stefan Bernhard, Medical Dissertation, Dissertation: "Interleukin 8 induced changes in the intracellular pH of neutrophil granulocytes", Publikation: "Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions"
• Stefan Hug, Medical Dissertation, Dissertation: "Experimental sepsis impairs neutrophil granulocyte activation by platelet-activating factor", Publikation: "Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis"
• Lukas Keßling, Medical Dissertation, "Judgement agreement between student and medical examiners"
• Rebecca Traut, Master Thesis, "Monitoring of Thromboinflammation as Immunomonitoring Method in Experimental and Clinical Sepsis"
• Leonard Schöbel, Master Thesis, "The Cellular Response capacity of neutrophils as a novel immunomonitoring method – a proof of concept study"
• Laura Vidoni, Master Thesis, "Definition of a sepsis-like immunophenotype of neutrophil granulocytes in a human ex vivo whole blood model"
• Maike Erber, Master Thesis, "Electrophysiological phenotype of neutrophil granulocytes during systemic inflammation"
• Bertram Thomaß, Bachelor Thesis, "Development of an analysis method for the distribution patterns of human granulocytes in flow cytometry"

• BioLAGO e.V. – The health network
• Dr. E. Chteinberg (Institute of Human Genetics, University Medical Center Ulm)
• Prof. Dr. F. Gebhard (Department of Orthopedic Trauma, Hand-, Plastic- and Reconstructive Surgery, University Medical Center Ulm)
• Dr. B. Hagemann (Institute for Medical Microbiology and Hygiene, University Medical Center Ulm)
• Prof. Dr. A. Liebold (Department of Cardiothoracic and Vascular Surgery, University Medical Center Ulm)
• PD Dr. D. Messerer (Department of Molecular Diagnostics, Molecular Therapy and Experimental Transplantation, Institute of Clinical Transfusion Medicine and Immunogenetics Ulm)
• Prof. Dr. B. Nilsson (Department of Immunology, Genetics and Pathology, University Uppsala, Schweden)
• Prof. Dr. K. Nilsson Ekdahl (Department of Immunology, Genetics and Pathology, University Uppsala, Linnæus Center of Biomaterials Chemistry, Schweden)
• PD Dr. C. Schmidt (Institute of Pharmacology of Natural Products and Clinical Pharmacology, Ulm University)
• Prof. Dr. M. Weiß, Prof. Dr. E. Barth (Department of Anaesthesiology and Intensive Care Medicine, University Medical Center Ulm)