Serum lipopolysaccharide-binding protein and soluble CD14 are markers of disease activity in patients with Crohn's disease.
BACKGROUND
In inflammatory bowel disease (IBD), enhanced inflammatory activity in the gut is thought to increase the risk of bacterial translocation and endotoxemia. In the present study we investigated the association between serum level of lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and clinical disease activity, high-sensitivity C-reactive protein (hs-CRP), antimicrobial serology profile, NOD2/CARD15 status, and clinical phenotype in a large cohort of Hungarian Crohn's disease (CD) patients.


METHODS
In all, 214 well-characterized, unrelated, consecutive CD patients (male/female ratio: 95/119; age: 35.6 ± 13.1 years; duration:8.3 ± 7.5 years) and 110 healthy controls were investigated. Sera were assayed for LBP, sCD14, hs-CRP, ASCA IgG/IgA, anti-OMP IgA, and pANCA antibodies. NOD2/CARD15 and TLR4 variants were tested. Detailed clinical phenotypes were determined by reviewing the patients' medical charts.


RESULTS
Serum LBP level was significantly higher (P < 0.0001 for both), while sCD14 was lower (P < 0.0001) in both active and inactive CD compared to the controls. The accuracy of hs-CRP (area under the curve [AUC] = 0.66), sCD14 (AUC = 0.70), and LBP (AUC = 0.58) was comparable for identifying patients with active disease. There was a significant correlation between LBP (P < 0.001), sCD14 (P = 0.015), and hs-CRP levels but not with antimicrobial seroreactivity or NOD2/CARD15 genotype. In inactive CD, LBP was associated with penetrating disease. In a Kaplan-Meier analysis and a proportional Cox-regression analysis, LBP (P = 0.006), sCD14 (P = 0.007), and previous relapse frequency (P = 0.023) were independently associated with time to clinical relapse during a 12-month follow-up period.


CONCLUSIONS
Serum LBP and sCD14 are markers of disease activity in CD with a similar accuracy as hs-CRP. In addition, LBP, sCD14, and a high frequency of previous relapses were independent predictors for 1-year clinical flare-up. (Inflamm Bowel Dis 2011).
Lakatos
Peter Laszlo
PL
1st Department of Medicine, Semmelweis University, Budapest, Hungary. kislakpet@bel1.sote.hu
Kiss
Lajos Sandor
LS
Palatka
Karoly
K
Altorjay
Istvan
I
Antal-Szalmas
Peter
P
Palyu
Eszter
E
Udvardy
Miklos
M
Molnar
Tamas
T
Farkas
Klaudia
K
Veres
Gabor
G
Harsfalvi
Jolan
J
Papp
Janos
J
Papp
Maria
M
D000209:Acute-Phase Proteins; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D003424:Crohn Disease / Q000097:blood* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics; D011379:Prognosis; D015996:Survival Rate; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D015415:Biomarkers; D002097:C-Reactive Protein; D002352:Carrier Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D053473:Nod2 Signaling Adaptor Protein; D000099231:Lipopolysaccharide-Binding Protein; C429018:NOD2 protein, human