Biomarkers in sepsis and other severe infections
Author
Summary, in English
The aim with this thesis was to study the cellular immune response with phenotypical assays, in patients with severe infections with focus on sepsis. We assessed if our findings could serve as biomarkers and provide valuable diagnostic and possible also therapeutic information.
In the first part (paper I) we examined surface markers on white blood cells from patients with severe infections. In some instances our analysis could differentiate between infections of bacterial and viral origin. In the second part (paper II-IV) we examined the incidence and nature of the immune alterations found in patients with sepsis and septic shock. We identified a protein (Wnt5a) that inhibited differentiation of monocytes to monocyte-derived myeloid dendritic cells (Mo-mDC), which may play a role in the DC depletion often seen in sepsis. Also, as indicated by cell surface phenotype, a large inter-individual variation of immune activation and immunosuppression was detected in patients with sepsis, with a dominance of immunosuppression in patients with septic shock. Finally, different types of immature myeloid immunosuppressive cells, myeloid-derived suppressor cells (MDSCs) were found in patients with sepsis; Mo-MDSCs were preferentially expanded in patients with gram-negative sepsis, whereas granulocytic MDSCs (PMN-MDSCs) accumulated in patients with gram-positive sepsis.
We conclude that the immune response during severe infections shows large inter-individual variations and biomarker guided therapy could be useful in individualised treatment.
Department/s
- Infectious Diseases Research Unit
Publishing year
2014
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2014:50
Full text
- Available as PDF - 10 MB
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Document type
Dissertation
Publisher
Department of Clinical Sciences, Lund University
Topic
- Clinical Medicine
Keywords
- immunosuppression
- myeloid-derived suppressor cells
- T cells
- dendritic cells
- monocytes
- sepsis
- Biomarkers
Status
Published
Research group
- Infectious Diseases Research Unit
Supervisor
- Karin Leandersson
- Marlene Wullt
- Anders Bredberg
- Tomas Leanderson
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-87651-76-2
Defence date
16 May 2014
Defence time
13:00
Defence place
The main lecture hall, Pathology Building, Skåne University Hospital, Malmö
Opponent
- Tomas Vikerfors