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Due to copyright issues, an electronic copy of the thesis must be ordered from the faculty. For the faculty to have time to process the order, the order must be received by the faculty at the latest 2 days before the public defence. Orders received later than 2 days before the defence will not be processed. After the public defence, please address any inquiries regarding the thesis to the candidate.
Trial Lecture – time and place
See Trial Lecture.
Adjudication committee
- First opponent: Professor Tomas Ganz, University of California, USA
- Second opponent: Associate Professor, Senior Consultant Cecilia Rydén, Lund University, Sweden
- Third member and chair of the evaluation committee: Professor Jens Petter Berg, University of Oslo
Chair of the Defence
Professor II Pål André Holme, University of Oslo
Principal Supervisor
Lars Heggelund, Professor, Senior Consultant, University of Bergen, Vestre Viken HF, Norway
Summary
Iron is indispensable to virtually all living organisms. Consequently, microbes try to exploit human iron to support their expansion, whereas humans aim to restrict the access of iron to invading microbes to prevent infections, a process called “the battle for iron”.
During infections, levels of iron and iron-related proteins in the circulation are known to change profoundly. We used biobank material from a prospective cohort of 267 hospitalized community-acquired pneumonia patients to assess the dynamics of iron and iron-related biomarkers during pneumonia, and to explore the potential of such biomarkers to predict microbial etiology and prognosis.
First, high admission levels of hepcidin (iron regulatory hormone) and ferritin (iron storage protein) were more likely in atypical bacterial infections and low values were more likely in viral infections. High ferritin levels were also more likely in atypical than typical bacterial infections.
Second, lower hepcidin levels at admission were associated with increased 5-year mortality compared to higher values, independent of age, sex, and number of comorbid conditions. There was no association with short-term outcome assessed by a combination of ICU admissions and 30-day mortality.
Third, the performance of two analytical principles of hepcidin measurements was compared. The methods were an LC-MS/MS method measuring the bioactive hepcidin-25 and an immunoassay also recognizing smaller isoforms of hepcidin. Different levels were expected from existing knowledge, but in the samples from the acute phase of the pneumonia, the difference increased with increasing hepcidin values.
According to these findings, iron-related biomarkers may aid assessment of microbial etiology (hepcidin and ferritin) and long-term prognosis (hepcidin). To interpret hepcidin measurements correctly, the characteristics of each analytical method and its expected values must be known, also during infections.
Additional information
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