249 Introduction Crohn’s disease (CD) is a chronic inflammatory disease that mainly affects the gastro-intestinal tract and is characterized by an inappropriate and ongoing immune response.1 Most patients suffer from a relapse-remitting disease course that is difficult to predict.2,3 Predicting the disease course is hampered by the poor availability of adequate disease biomarkers or symptoms that forecast a flare of inflammation. Longstanding sub-clinical disease activity increases the risk of various severe complications, such as stricturing or penetrating disease (i.e. fistula or abscess formation).4 Appropriate and prompt treatment of the inflammatory activity lowers the risk of these severe complications, and thus prevents future surgical interventions. Currently, the only reliable approach for diagnosis of CD is an invasive ileo-colonoscopy. However, this procedure has several disadvantages, such as the risk of perforation, bleeding, relatively high costs and, most importantly, a high patient burden. Furthermore, a poor association exists between patient-reported symptoms and the observed endoscopic inflammatory activity. For instance, clinical risk scores, such as the Harvey Bradshaw Index (HBI) or the Crohn’s Disease Activity Index (CDAI), cannot accurately predict active intestinal inflammation.5,6 In clinical practice, fecal calprotectin levels are commonly used as non-invasive biomarker that significantly correlates with inflammatory disease activity and response to therapy.5,7-10 Calprotectin is a 36 kDa calcium- and zinc-binding protein dimer (consisting of S100A8 and S100A9) complex present in the cytosol of neutrophilic granulocytes.11,12 Fecal calprotectin levels are representative of neutrophil migration into the intestinal mucosa that occurs in the process of intestinal inflammation. Despite its proven association with disease activity, the diagnostic accuracy may be further improved by inclusion of additional biomarkers for active inflammation and/or tissue injury in CD.12-14 Many cytokines have been shown to be involved in disease pathogenesis and might give a more accurate representation of the inflammatory activity in CD relapses in combination with fecal calprotectin levels. Ultimately, this may aid in an improved detection of active disease and a more versatile and effective treatment. A Th1-driven immune response with increased Th1-associated cytokines such as IFN-γ and TNF-α plays a pivotal role in the pathogenesis of CD.15 The importance of Th1-responses is also reflected by the clinical use of TNF-α antagonists, such as infliximab, adalimumab and certolizumab, which are effective treatment modalities in CD.16 Previously, quantification of cytokines for diagnosis of disease has been cumbersome due to low serum concentrations of the relevant cytokines, but new techniques enable us to quantify most cytokines in a highly sensitive, reproducible and validated manner.17-19 The aim of this study is to identify potential serum cytokines, chemokines and markers for angiogenesis and vascular injury that might serve as additional biomarkers for inflammatory disease activity in CD. A positive correlation between specific serum biomarkers and fecal calprotectin levels might enhance the diagnostic potential for early recognition of disease exacerbations. Inflammatory proteins in Crohn’s disease
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