Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases.
OBJECTIVE
There is an unmet need for novel blood-based biomarkers that offer timely and accurate diagnostic and prognostic testing in inflammatory bowel diseases (IBD). We aimed to investigate the diagnostic and prognostic utility of serum calprotectin (SC) in IBD.


METHODS
A total of 171 patients (n=96 IBD, n=75 non-IBD) were prospectively recruited. A multi-biomarker model was derived using multivariable logistic regression analysis. Cox proportional hazards model was derived to assess the contribution of each variable to disease outcomes.


RESULTS
SC correlated strongly with current biomarkers, including fecal calprotectin (FC) (n=50, ρ=0.50, P=1.6 × 10-4). SC was the strongest individual predictor of IBD diagnosis (odds ratio (OR): 9.37 (95% confidence interval (CI): 2.82-34.68), P=4.00 × 10-4) compared with other markers (C-reactive protein (CRP): OR 8.52 (95% CI: 2.75-28.63), P=2.80 × 10-4); albumin: OR 6.12 (95% CI: 1.82-22.16), P=0.004). In a subset of 50 patients with paired SC and FC, the area under receiver operating characteristic discriminating IBD from controls was better for FC than for SC (0.99, (95% CI 0.87-1.00) and 0.87 (95% CI:0.78-0.97), respectively; P=0.01). At follow-up (median 342 days; interquartile range: 88-563), SC predicted treatment escalation and/or surgery in IBD (hazard ratio (HR) 2.7, 95% CI: 1.1-4.9), in particular Crohn's disease (CD) (HR 4.2, 95% CI 1.2-15.3). A model incorporating SC and either CRP or albumin has a positive likelihood ratio of 24.14 for IBD. At 1 year, our prognostic model can predict treatment escalation in IBD in 65% of cases (95% CI: 43-79%) and 80% (95% CI: 31-94%) in CD if ≥2 blood marker criteria are met.


CONCLUSIONS
A diagnostic and prognostic model that combines SC and other blood-based biomarkers accurately predicts the inflammatory burden in IBD and has the potential to predict disease and its outcomes. Our data warrant further detailed exploration and validation in large multicenter cohorts.
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Rahul
R
Kalla
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Nicholas A
NA
Kennedy
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Nicholas T
NT
Ventham
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.|Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Ray K
RK
Boyapati
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Alex T
AT
Adams
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Elaine R
ER
Nimmo
Metabolic Bone Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Micaela R
MR
Visconti
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Hazel
H
Drummond
Centre for Inflammation Research, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Gwo-Tzer
GT
Ho
Department of Clinical Chemistry, Western General Hospital, NHS Lothian, Edinburgh, UK.
Rebecca J
RJ
Pattenden
Child Life and Health, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.
David C
DC
Wilson
Gastrointestinal Unit, Centre for Molecular Medicine, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
Jack
J
Satsangi
D000328:Adult; D019540:Area Under Curve; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D003424:Crohn Disease / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012709:Serum Albumin / Q000378:metabolism; D055815:Young Adult
D039841:Leukocyte L1 Antigen Complex; D012709:Serum Albumin; D002097:C-Reactive Protein