A comparison of high-mobility group-box 1 protein, lipopolysaccharide-binding protein and procalcitonin in severe community-acquired infections and bacteraemia: a prospective study.
BACKGROUND
High-mobility group box-1 protein (HMGB1) has been known as a chromosomal protein for many years. HMGB1 has recently been shown to be a proinflammatory cytokine with a role in the immunopathogenesis of sepsis. Lipopolysaccharide-binding protein (LBP) has a central role in the innate immune response when the host is challenged by bacterial pathogens. Procalcitonin (PCT) has been suggested as a marker of severe bacterial infections and sepsis. The aim of the present study was to investigate levels of HMGB1, LBP and PCT in a well-characterised sepsis cohort. The study plan included analysis of the levels of the inflammatory markers in relation to the severity of infection, to the prognosis and to the ability to identify patients with bacteraemia.


METHODS
Patients suspected of having severe infections and admitted to a department of internal medicine were included in a prospective manner. Demographic data, comorbidity, routine biochemistry, microbiological data, infection focus, severity score and mortality on day 28 were recorded. Plasma and serum were sampled within 24 hours after admission. Levels of all studied markers (HMGB1, LBP, PCT, IL-6, C-reactive protein, white blood cell count and neutrophils) were measured with commercially available laboratory techniques.


RESULTS
A total of 185 adult patients were included in the study; 154 patients fulfilled our definition of infection. Levels of HMGB1, LBP and PCT were higher in infected patients compared with a healthy control group (P < 0.0001). Levels of HMGB1, LBP and PCT were higher in the severe sepsis group compared with the sepsis group (P < 0.01). No differences were observed in levels of the inflammatory markers in fatal cases compared with survivors. Levels of all studied markers were higher in bacteraemic patients compared with nonbacteraemic patients (P < 0.05). PCT performed best in a receiver-operator curve analysis discriminating between bacteraemic and nonbacteraemic patients (P < 0.05). HMGB1 correlated to LBP, IL-6, C-reactive protein, white blood cell count and neutrophils (P < 0.001). LBP correlated to PCT, IL-6 and C-reactive protein (P < 0.001).


CONCLUSIONS
Levels of HMGB1, PCT and LBP were higher in infected patients compared with those in healthy controls, and levels were higher in severe sepsis patients compared with those in sepsis patients. Levels of all studied inflammatory markers (HMGB1, LBP, PCT, IL-6) and infection markers (C-reactive protein, white blood cell count, neutrophils) were elevated among bacteraemic patients. PCT performed best as a diagnostic test marker for bacteraemia.
Gaïni
Shahin
S
Department of Infectious Diseases, Odense University Hospital, Søndre Boulevard 29, DK-5000 Odense C, Denmark. shahin.gaini@ouh.regionsddanmark.dk
Koldkjaer
Ole G
OG
Møller
Holger J
HJ
Pedersen
Court
C
Pedersen
Svend S
SS
D000209:Acute-Phase Proteins; D000368:Aged; D016470:Bacteremia / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D002352:Carrier Proteins / Q000097:blood*; D017714:Community-Acquired Infections / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D003718:Denmark / Q000453:epidemiology; D005260:Female; D024243:HMGB1 Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012720:Severity of Illness Index; D016019:Survival Analysis; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D015415:Biomarkers; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide; D002352:Carrier Proteins; D024243:HMGB1 Protein; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D000099231:Lipopolysaccharide-Binding Protein; C000606589:CALCA protein, human