Lipopolysaccharide-Binding Protein:A New Biomarker forInfectious Endocarditis?
and Jens Dreier
Infectious endocarditis (IE) is a bacterialinfection of the endocardium. Diagnosis is based onresults obtained from echocardiography, blood cul-tures, and molecular genetic screening for bacteria andon data for inflammatory markers such as the leuko-cyte (WBC) count and the C-reactive protein (CRP)concentration. The aim of the present study was toevaluatelipopolysaccharide-bindingprotein(LBP)asasupportive biomarker for the diagnosis and therapeu-tic monitoring of IE.
We measured LBP and CRP concentrationsand WBC counts in 57 IE patients at hospital admis-sion, 40 patients with noninfectious heart valve dis-eases (HVDs), and 55 healthy blood donors. The pro-gressionofthese3markersandtheinfluenceofcardiacsurgeryonthemwereevaluatedin29IEpatientsand21control patients.
Serum LBP concentrations were significantly higher in IE patients [mean (SD), 33.41 (32.10) mg/L]compared with HVD patients [6.67 (1.82) mg/L,
0.0001] and healthy control individuals [5.61 (1.20)mg/L]. The progression in the LBP concentration dur-ingtherapyofIEpatientscorrelatedwiththechangesinthe CRP concentration. The 2 markers were equally influenced by antibiotic treatment and surgicalintervention.
SerialLBPmeasurementmayprovideaneffective and useful tool for evaluating the response totherapy in IE patients. We found a strong correlationbetween LBP and CRP concentrations; LBP has a ten-dency to increase earlier in cases of reinfection.
© 2008 American Association for Clinical Chemistry
Infectious endocarditis (IE),
a relatively rare diseasewith an incidence of 30 per million population
, isassociated with high rates of mortality and morbidity.Rapid diagnosis of IE is critical for effective treatment.Diagnosis is based primarily on the results of echocar-diographicexaminationsandbloodculturetests[Dukecriteria
], as well as on the results of serology testsand molecular genetic screening methods for bacteriain cases of heart valve replacement
. The initialdiagnosis of IE can be difficult, however, because of nonspecific clinical symptoms, negative results inblood cultures, and ambiguous echocardiographicfindings. In this context, the availability of biomarkersis of major interest. Several studies have investigatedthe application and usefulness of important laboratory markersforIEdiagnosis
have focused on the clinical usefulness of serum C-reactive protein (CRP), a marker most frequently usedin Europe
, in IE. CRP has been assumed to beprimarily an indicator of local bacterial infections, butincreased CRP concentrations have also been strongly associated with various nonbacterial infectious dis-eases, e.g., rheumatic disorders
. CRP has beenshown to have a limited ability to distinguish betweenbacterial and viral infections
.Lipopolysaccharide-binding protein (LBP), a gly-cosylated 58-kDa protein produced predominantly inhepatocytes,hasrecentlybeendescribedasapromisingnovel diagnostic marker for the diagnosis of local bac-terial infection
. LBP is released constitutively into the bloodstream upon acute-phase stimulation
. It has a high affinity for lipopolysaccharide (LPS)and other bacterial-surface components
. Bindingof LPS to LBP facilitates the transportation of endo-toxin molecules to immune effector cells possessingsurfaceCD14receptorsandfurtheractivatestheproin-flammatory cascade
. Association of the LPS/
Institut fu¨r Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszen-trum Nordrhein-Westfalen, Universita¨tsklinik der Ruhr-Universita¨t Bochum, BadOeynhausen, Germany;
Klinik fu¨r Kardiologie, Herz- und DiabeteszentrumNordrhein-Westfalen, Universita¨tsklinik der Ruhr-Universita¨t Bochum, BadOeynhausen, Germany.* Address correspondence to this author at: Institut fu¨r Laboratoriums- undTransfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Univer-sita¨tsklinik der Ruhr-Universita¨t Bochum, Georgstrasse 11, 32545 Bad Oeyn-hausen, Germany. Fax
49-5731-97-2307; e-mail email@example.com.Received March 4, 2008; accepted August 26, 2008.Previously published online at DOI: 10.1373/clinchem.2008.106195
Nonstandard abbreviations: IE, infectious endocarditis; CRP, C-reactive protein;LBP, lipopolysaccharide-binding protein; LPS, lipopolysaccharide; HVD, nonin-fectious heart valve disease; WBC, leukocyte; CI, confidence interval.
Proteomics and Protein Markers