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Sustained elevation of soluble B- and T- lymphocyte attenuator predicts long-term mortality in patients with bacteremia and sepsis
Örebro University, School of Medical Sciences. Department of Infectious Diseases.ORCID iD: 0000-0001-7679-7253
Örebro University, School of Medical Sciences. Department of Infectious Diseases.
Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden.
Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
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(English)Manuscript (preprint) (Other academic)
National Category
Infectious Medicine
Identifiers
URN: urn:nbn:se:oru:diva-81440OAI: oai:DiVA.org:oru-81440DiVA, id: diva2:1427909
Available from: 2020-05-04 Created: 2020-05-04 Last updated: 2020-05-04Bibliographically approved
In thesis
1. SLPI and soluble BTLA as immunological markers in severe bacterial infections
Open this publication in new window or tab >>SLPI and soluble BTLA as immunological markers in severe bacterial infections
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Clinical presentation, and outcome of infections are affected by host-, and etiology- (focus of infection and pathogen) related factors. The immune response is controlled by a network of regulating pathways.

This thesis focuses on Secretory Leukocyte Protease Inhibitor (SLPI), a protease inhibitor with anti-inflammatory properties, and the previously non-studied soluble isoform of B and T lymphocyte attenuator (sBTLA), a membrane-associated regulatory protein. Plasma concentrations of SLPI and sBTLA were assessed in relation to etiology, severity, mortality, and markers of inflammation and immunosuppression, in i) community-acquired pneumonia (CAP) (SLPI), ii) intensive care unit (ICU) treated severe sepsis and septic shock (sBTLA), and iii) dynamically in BSI (SLPI and sBTLA).

Main findings were: higher expression of SLPI in pneumonia, compared to other sources, higher initial concentrations in Streptococcus pneumoniae, and Staphylococcus aureus BSI, compared to Escherichia coli BSI, and higher SLPI concentrations in sepsis compared to non-septic BSI. Interestingly, men with pneumonia had higher plasma levels of SLPI, both in CAP and BSI. Likewise, sBTLA was associated with severity, but preferentially at higher organ failure scores. High sBTLA was associated with increased risk of early death (28 days) in ICU-treated septic patients, and with mortality at 90 days and one year in BSI. In particular, failure to normalize sBTLA on day 7, was indicative of worse long-term outcome. SLPI was associated with decreased monocytic HLA-DR expression, and sBTLA with decreased lymphocyte count, which might indicate a connection to sepsis-associated immunosuppression.

In conclusion, SLPI and sBTLA show association with severity, and markers of immune dysfunction, in sepsis and BSI. SLPI differs depending on etiology, while sBTLA may have prognostic implications. Our results propose that the pathobiological role of sBTLA, and the possible utility of SLPI and sBTLA in sepsis immune-profiling, should be further addressed in future studies.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 82
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 211
Keywords
SLPI, sBTLA, sepsis, bloodstream infection, pneumonia
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-80161 (URN)978-91-7529-335-6 (ISBN)
Public defence
2020-05-29, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2020-02-24 Created: 2020-02-24 Last updated: 2020-05-13Bibliographically approved

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Lange, AnnaCajander, SaraHultgren, Olof

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