Scandinavian Journal of Gastroenterology. 2015; Early Online, 1–2
LETTER TO THE EDITOR
Correspondence: fecal calprotectin and cut-off levels in inflammatory bowel disease
Scand J Gastroenterol Downloaded from informahealthcare.com by East Carolina University on 04/20/15 For personal use only.
VENDEL KRISTENSEN1,2 & BJØRN MOUM2,3 1
Department of Medicine, Unger-Vetlesens Institute, Lovisenberg Diakonale Hospital, Oslo, Norway, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and 3Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
2
Dear Editor, We read with interest the review article of Sipponen et al. discussing fecal calprotectin (FC) in diagnosis and clinical assessment of inflammatory bowel disease (IBD) [1]. Their conclusion is that FC cut-off levels differentiating grades of mucosal inflammation in IBD are non-existent and probably difficult to achieve. In a table of proposed cut-off levels, they nicely demonstrate the diversity in FC cut-off levels found to predict relapse in IBD patients in clinical remission. We believe that some of this substantial variation in cut-off levels may be due to different ELISA manufacturers used in these studies. We have recently demonstrated that the optimal FC cut-off level differentiating endoscopically active from inactive ulcerative colitis (UC) depends on the ELISA assay used for FC analysis [2]. Sipponen et al. refer to two different studies investigating FC cut-off levels differentiating endoscopically active IBD from IBD in endoscopical remission. One of these studied only Crohn’s disease (CD) patients and found 100 mg/g FC as the optimal cut-off level using an ELISA assay from Calpro AS, Oslo, Norway [3], a level corresponding very well with our findings using the same assay from Calpro AS, but in UC patients, namely 110 mg/g FC [2]. The other reference investigated both UC and CD patients and concluded with a cut-off level of 250 mg/g FC [4]. This may be considered a conflicting result, but the latter study used an ELISA assay from Genova Diagnostics, Asheville, North Carolina,
USA, which may not be comparable to the Calpro assay. In our study, we investigated an assay manufactured by Bühlmann Laboratories, Schönenbuch, Switzerland, where the cut-off level differentiating endoscopically active UC from inactive was 259 mg/g FC [2]. We also demonstrated that even a discrete mucosal inflammation affected the levels of FC, resulting in lower cut-off levels (Calpro 61 mg/g FC and Bühlmann 96 mg/g) if only Mayo 0 (i.e., normal endoscopy) was accepted as endoscopical remission. Therefore, one should investigate whether histological inflammation in an endoscopically normal mucosa would contribute to elevated FC, and consider if adding histopathology as a variable might improve diagnostic accuracy. Future studies evaluating clinical outcome in IBD patients and FC cut-off levels should therefore consider which assay has been used, as FC cut-off levels must be tailored and validated for each ELISA assay individually. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Sipponen T, Kolho KL. Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease. Scand J Gastroenterol 2015;50:74–80.
Correspondence: Vendel Kristensen, Department of Medicine, Unger-Vetlesens Institute, Lovisenberg Diakonale Hospital, Oslo 0440, Norway. E-mail: vendel@vikenfiber.no
(Received 26 February 2015; accepted 28 February 2015) ISSN 0036-5521 print/ISSN 1502-7708 online 2015 Informa Healthcare DOI: 10.3109/00365521.2015.1025830
2
V. Kristensen & B. Moum
Scand J Gastroenterol Downloaded from informahealthcare.com by East Carolina University on 04/20/15 For personal use only.
[2] Kristensen V, Klepp P, Cvancarova M, Roseth A, Skar V, Moum B. Prediction of endoscopic disease activity in ulcerative colitis by two different assays for faecal calprotectin. J Crohns Colitis 2014. [Epub ahead of print]. [3] Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Farkkila M. Crohn’s disease activity assessed by fecal
calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis 2008;14:40–6. [4] D’Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2218–24.
LETTER TO THE EDITOR
Correspondence: fecal calprotectin and cut-off levels in inflammatory bowel disease
Scand J Gastroenterol Downloaded from informahealthcare.com by East Carolina University on 04/20/15 For personal use only.
VENDEL KRISTENSEN1,2 & BJØRN MOUM2,3 1
Department of Medicine, Unger-Vetlesens Institute, Lovisenberg Diakonale Hospital, Oslo, Norway, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and 3Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
2
Dear Editor, We read with interest the review article of Sipponen et al. discussing fecal calprotectin (FC) in diagnosis and clinical assessment of inflammatory bowel disease (IBD) [1]. Their conclusion is that FC cut-off levels differentiating grades of mucosal inflammation in IBD are non-existent and probably difficult to achieve. In a table of proposed cut-off levels, they nicely demonstrate the diversity in FC cut-off levels found to predict relapse in IBD patients in clinical remission. We believe that some of this substantial variation in cut-off levels may be due to different ELISA manufacturers used in these studies. We have recently demonstrated that the optimal FC cut-off level differentiating endoscopically active from inactive ulcerative colitis (UC) depends on the ELISA assay used for FC analysis [2]. Sipponen et al. refer to two different studies investigating FC cut-off levels differentiating endoscopically active IBD from IBD in endoscopical remission. One of these studied only Crohn’s disease (CD) patients and found 100 mg/g FC as the optimal cut-off level using an ELISA assay from Calpro AS, Oslo, Norway [3], a level corresponding very well with our findings using the same assay from Calpro AS, but in UC patients, namely 110 mg/g FC [2]. The other reference investigated both UC and CD patients and concluded with a cut-off level of 250 mg/g FC [4]. This may be considered a conflicting result, but the latter study used an ELISA assay from Genova Diagnostics, Asheville, North Carolina,
USA, which may not be comparable to the Calpro assay. In our study, we investigated an assay manufactured by Bühlmann Laboratories, Schönenbuch, Switzerland, where the cut-off level differentiating endoscopically active UC from inactive was 259 mg/g FC [2]. We also demonstrated that even a discrete mucosal inflammation affected the levels of FC, resulting in lower cut-off levels (Calpro 61 mg/g FC and Bühlmann 96 mg/g) if only Mayo 0 (i.e., normal endoscopy) was accepted as endoscopical remission. Therefore, one should investigate whether histological inflammation in an endoscopically normal mucosa would contribute to elevated FC, and consider if adding histopathology as a variable might improve diagnostic accuracy. Future studies evaluating clinical outcome in IBD patients and FC cut-off levels should therefore consider which assay has been used, as FC cut-off levels must be tailored and validated for each ELISA assay individually. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. References [1] Sipponen T, Kolho KL. Fecal calprotectin in diagnosis and clinical assessment of inflammatory bowel disease. Scand J Gastroenterol 2015;50:74–80.
Correspondence: Vendel Kristensen, Department of Medicine, Unger-Vetlesens Institute, Lovisenberg Diakonale Hospital, Oslo 0440, Norway. E-mail: vendel@vikenfiber.no
(Received 26 February 2015; accepted 28 February 2015) ISSN 0036-5521 print/ISSN 1502-7708 online 2015 Informa Healthcare DOI: 10.3109/00365521.2015.1025830
2
V. Kristensen & B. Moum
Scand J Gastroenterol Downloaded from informahealthcare.com by East Carolina University on 04/20/15 For personal use only.
[2] Kristensen V, Klepp P, Cvancarova M, Roseth A, Skar V, Moum B. Prediction of endoscopic disease activity in ulcerative colitis by two different assays for faecal calprotectin. J Crohns Colitis 2014. [Epub ahead of print]. [3] Sipponen T, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Farkkila M. Crohn’s disease activity assessed by fecal
calprotectin and lactoferrin: correlation with Crohn’s disease activity index and endoscopic findings. Inflamm Bowel Dis 2008;14:40–6. [4] D’Haens G, Ferrante M, Vermeire S, Baert F, Noman M, Moortgat L, et al. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2218–24.
