SLPI and soluble BTLA as immunological markers in
severe bacterial infections
av
Anna Lange
Akademisk avhandling
Avhandling för medicine doktorsexamen i medicinsk vetenskap, inriktning medicin
som kommer att försvaras offentligt fredagen den 29 maj 2020 kl. 09.00, Hörsal C1, Campus USÖ, Örebro Universitet
Opponent: Docent Peter Bergman Karolinska Institutet
Stockholm
Örebro universitet
Institutionen för medicinska vetenskaper 701 82 ÖREBRO
Abstract
Anna Lange (2020): SLPI and soluble BTLA as immunological markers in severe bacterial infections. Örebro Studies in Medicine 211.
Clinical presentation, and outcome of infections are affected by host-, and etiology- (focus of infection and pathogen) related factors. The im-mune 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, com-pared 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 out-come. SLPI was associated with decreased monocytic HLA-DR expres-sion, 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 ad-dressed in future studies.
Keywords: SLPI, sBTLA, sepsis, bloodstream infection, pneumonia
Anna Lange, School of health and Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-70182 Örebro, Sweden, anna.lange@regionorebrolan.se
