Serum Calprotectin: A Novel Diagnostic and Prognostic Marker in Inflammatory Bowel Diseases

IntroductionThere 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.MethodsA 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.ResultsSC correlated strongly with current biomarkers including faecal calprotectin (FC) (n=50, rho= 0.50, p=1.6x10-437 ). SC was the strongest individual predictor of IBD diagnosis (odds ratio (OR): 9.37(95%CI: 2.82-34.68), p=4.00×10-438 ) compared with other markers (CRP: OR 8.52(95%CI: 2.75-28.63), p=2.80×10-439 ); 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 SC (0.99, (95% CI 0.87-1.00) and 0.87 (95% CI:0.78-0.97) respectively; p=0.01).43 At follow up (median 342 days; IQR: 88-563), SC predicted treatment escalation and/or44 surgery in IBD (HR 2.7, 95% CI: 1.1-4.9), in particular CD (HR 4.2, 95% CI 1.2-15.3).Page 2 of 73ScholarOne, 375 Greenbrier Drive, Charlottesville, VA, 22901American Journal of GastroenterologyFor Peer Review3A model incorporating SC and either CRP or albumin has a positive likelihood 45 ratio of 24.1446 for IBD. At 1 year, our prognostic model can predict treatment escalation in IBD in 65% of47 cases (95% CI: 43-79%) and 80% (95% CI: 31-94%) in CD if 2 or more blood marker48 criteria are met.49 Conclusions50 A diagnostic and prognostic model that combines SC and other blood-based biomarkers51 accurately predicts the inflammatory burden in IBD and has the potential to predict disease52 and its outcomes. Our data warrants further detailed exploration and validation in large multi53centre cohorts.