scholarly journals Experimental infectious challenge in pigs leads to elevated fecal calprotectin levels following colitis, but not enteritis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jéssica A. Barbosa ◽  
Lucas A. Rodrigues ◽  
Daniel A. Columbus ◽  
Juan C. P. Aguirre ◽  
John C. S. Harding ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Point Of Care ◽  
Sandwich Elisa ◽  
Fecal Calprotectin ◽  
Field Application ◽  
Dipstick Test ◽  
Fecal Samples ◽  
Brachyspira Hyodysenteriae ◽  
Non Invasive ◽  
Serovar Typhimurium

Abstract Background Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. Results Fecal samples from pigs with colitis (n = 18) were collected from animals experimentally inoculated with B. hyodysenteriae (n = 8) or from sham-inoculated controls (n = 3). Fecal samples from pigs with enteritis (n = 14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium (n = 8) or from sham-inoculated controls (n = 4). For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method. Conclusions Fecal calprotectin levels are increased following the development of colitis, but do not significantly change due to enteritis. While practical, the use of commercially available human kits present sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker of intestinal inflammation.

Evaluation of Human Fecal Calprotectin Detection Kits and Their Potential use as Non-Invasive Intestinal Biomarker of Infectious Enterocolitis in Pigs

2021 ◽  
Author(s):  
Jéssica Barbosa ◽  
Lucas Rodrigues ◽  
Daniel Columbus ◽  
Juan Aguirre ◽  
John Harding ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Point Of Care ◽  
Sandwich Elisa ◽  
Fecal Calprotectin ◽  
Field Application ◽  
Dipstick Test ◽  
Infectious Colitis ◽  
Fecal Samples ◽  
Non Invasive ◽  
Infectious Enterocolitis

Abstract Background: Fecal calprotectin is largely applied as a non-invasive intestinal inflammation biomarker in human medicine. Previous studies in pigs investigated the levels of fecal calprotectin in healthy animals only. Thus, there is a knowledge gap regarding its application during infectious diarrhea. This study investigated the usefulness of fecal calprotectin as a biomarker of intestinal inflammation in Brachyspira hyodysenteriae and Salmonella Typhimurium infected pigs. Results: Fecal samples from pigs with colitis (n=18) were collected from animals experimentally inoculated with B. hyodysenteriae G44 or from sham-inoculated controls. Fecal samples from pigs with enteritis (n=14) were collected from animals inoculated with Salmonella enterica serovar Typhimurium or from sham-inoculated controls. For both groups, fecal samples were scored as: 0 = normal; 1 = soft, wet cement; 2 = watery feces; 3 = mucoid diarrhea; and 4 = bloody diarrhea. Fecal calprotectin levels were assayed using a sandwich ELISA, a turbidimetric immunoassay and a point-of-care dipstick test. Fecal calprotectin levels were greater in colitis samples scoring 4 versus ≤ 4 using ELISA, and in feces scoring 3 and 4 versus ≤ 1 using immunoturbidimetry (P < 0.05). No differences were found in calprotectin concentration among fecal scores for enteritis samples, regardless of the assay used. All samples were found below detection limits using the dipstick method.Conclusions: Fecal calprotectin is a potential non-invasive biomarker of infectious colitis, but it is not suitable for detection of enteritis. While practical, the use of commercially available human presents sensitivity limitations. Further studies are needed to validate the field application of calprotectin as a marker.

scholarly journals Role of Fecal Calprotectin as a Noninvasive Indicator for Ulcerative Colitis Disease Activity

Folia Medica ◽  
2019 ◽  
Vol 61 (2) ◽  
pp. 188-196 ◽  
Author(s):  
Radislav V. Nakov ◽  
Ventsislav N. Nakov ◽  
Vanya A. Gerova ◽  
Lyudmila T. Tankova
Keyword(s):  
Ulcerative Colitis ◽  
Disease Activity ◽  
Intestinal Inflammation ◽  
Point Of Care ◽  
Fecal Calprotectin ◽  
Non Invasive ◽  
Significant Difference ◽  
Endoscopic Score ◽  
Index Of Severity

Abstract Background: It is essential in clinical management to determine the disease activity in ulcerative colitis (UC) patients. At present, the most accurate way of evaluating the UC severity is endoscopy with biopsy. Fecal calprotectin (FCP) is a non-invasive biomarker that is frequently used for monitoring of intestinal inflammation. Aims: The purpose of our study was to assess the role of FCP as a noninvasive indicator for UC disease activity. Materials and methods: This prospective study enrolled 116 patients with UC (56 with quiescent UC and 60 with active UC) and 36 controls, referred for colonoscopy to our Center. Colonoscopy was performed in all the patients and the findings were graded according to Mayo endoscopic score (EMS) and UC endoscopic index of severity (UCEIS). FCP was analyzed in stool samples by means of point-of-care desk-top Quantum Blue® method. Results: There was no significant difference between mean FCP levels in controls and UC patients in remission (р=0.205). Mean FCP in patients with active UC was significantly higher than that in controls (p<0.001) and in patients in remission (p<0.001). FCP significantly correlated with UCEIS (r = 0.869, p<0.001) and EMS (r = 0.814, p<0.001). Conclusion: The strong correlation with endoscopic disease activity suggests that FCP is a useful biomarker for noninvasive diagnosis and monitoring of disease activity in UC patients.

Fecal Calprotectin In Allogeneic Stem Cell Trasplantation as Surrogate Marker of Gastrointestinal Graft Versus Host Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2327-2327
Author(s):  
Mariana Bastos Oreiro ◽  
Ana Lopez de la Guia ◽  
Jose B Nieto ◽  
Raquel De Paz ◽  
Patricia Baltasar ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Predictive Value ◽  
Intestinal Inflammation ◽  
Intestinal Parasites ◽  
Conditioning Regimen ◽  
Surrogate Marker ◽  
Fecal Calprotectin ◽  
Host Disease ◽  
Graft Versus Host ◽  
Non Invasive

Abstract Abstract 2327 Background: Calprotectin is a major cytosolic protein of neutrophils that have showed to be a sensitive marker of intestinal inflammation. The aim of our study has been to evaluate fecal calprotectin (FC) as a diagnosis tool in patients with acute gastrointestinal graft versus host disease (GI GVHD). Methods: Since March 2009, patients with suspicion of acute GI GVHD were consecutively included. Patients were tested for FC (reference range: 0–30 mg/kg) before starting treatment. Infections by Clostridium difficile, cytomegalovirus, fecal bacteria and intestinal parasites were also excluded. Colonoscopy was performed in all patients and biopsy samples were taken for histopathological examination. Results: To date, eleven patients have been included. The median age was 48.2 (r: 21–67). Indications for transplantation included acute myeloid leukemia (6 patients), myelodysplastic syndrome (2 patients), acute lymphoid leukemia, severe aplastic anemia and refractory follicular lymphoma (1 patient, respectively). Ten patients received myeloablative conditioning and one received reduced intensity conditioning regimen. Five patients were histologically diagnosed with acute GI GVHD. The median for FC in this group was 510.5 (r: 107.4–629). The median of FC in patients without GI GVHD was 117 (r: 13.9–205). Patients with GI GVHD had higher values of FC than patients without GI GVHD (p:≤0,009) For a cut-off point value of 205, sensitivity for the test was 83.3% (IC 61.3–100%), specificity was 100%, positive predictive value was 100%, and negative predictive value was 83.3% (IC 61.3–100%). In 3 patients who were diagnosed with cytomegalovirus enteritis and had no criteria for GI GVHD, the FC values were 15.4, 105, and 100.7. In a patient with Candida spp. infection FC was 13.9. The FC was higher in patients with grade IV GI GVHD, with median of 590 (r: 502–629). Conclusion: FC appears to be a promising non-invasive biomarker of acute GI GVHD. If these findings are confirmed, it may provide a useful non-invasive test for the diagnosis of GI GVHD in patients following allogeneic transplantation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Development and Validation of a Fecal Extraction Procedure for the Assessment of Multiple Fecal Biomarkers of Intestinal Inflammation (P13-025-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Erin Lewis ◽  
Weimin Guo ◽  
Lijun Li ◽  
Dayong Wu ◽  
Gerald Combs ◽  
...  
Keyword(s):  
Intestinal Inflammation ◽  
Agricultural Research ◽  
Sandwich Elisa ◽  
Extraction Procedure ◽  
Predictive Biomarkers ◽  
Healthy Adults ◽  
Tween 20 ◽  
Fecal Samples ◽  
Single Extraction ◽  
Fecal Biomarkers

Abstract Objectives Fecal biomarkers have emerged as an important tool to assess intestinal inflammation and permeability. Commonly measured biomarkers include calprotectin (CP), myeloperoxidase (MPO), alpha-1-antitrypsin (AAT) and neopterin (NEO). We sought to develop a simple, fast and cost-effective single extraction procedure for use in determining all four biomarkers of interest. The applicability and sensitivity of this procedure for use in healthy adults was examined. Methods Sample extraction buffers and methods including sample weight, dilution, homogenization and centrifugation were all considered in the development of a single extraction procedure. An extraction buffer that included phosphate-buffered saline, phenylmethylsulfonyl fluoride, bovine serum albumin and Tween 20 was used to extract fecal samples. To assess the applicability and sensitivity of the single extraction procedure, concentrations of CP, MPO, AAT and NEO were measured using commercially available sandwich ELISA kits, according to manufacturer's instructions. Results CP, MPO and AAT concentrations were measured in fecal samples of healthy adults (aged 50–80 years, n = 85) and found to be comparable to findings of previously published studies in healthy populations. Mean concentrations of CP and AAT were 3.6 ± 3.8 µg/g of wet weight (range 0.14–18.0 µg/g) and 2.3 ± 0.73 µg/g (range 0.76–5.2 µg/g), respectively. Mean fecal MPO concentrations were 135 ± 24 ng/g (range 3–1290 ng/g). NEO concentrations were examined in a subset of healthy adults (n = 10), with mean concentrations of 18 ± 1 ng/g (range 17–20 ng/g). Conclusions We demonstrated the efficacy of a single extraction procedure used to assess multiple fecal biomarkers of intestinal inflammation. This simple, fast and inexpensive extraction method will facilitate the determination of multiple fecal biomarkers which is critical in validating their use as clinical or predictive biomarkers of intestinal inflammation. Funding Sources Supported by the U.S. Department of Agriculture – Agricultural Research Service (ARS), under Agreement No. 58–1950-4–003, the Bill & Melinda Gates Foundation and Canadian Institutes of Health Research Postdoctoral Fellowship.

scholarly journals Calprotectin as a marker of bowel inflammation

2013 ◽  
Author(s):  
Gianluca Terrin ◽  
Andrea Pietravalle
Keyword(s):  
Inflammatory Process ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Functional Gastrointestinal Disorders ◽  
Gastrointestinal Symptoms ◽  
Fecal Calprotectin ◽  
Bacterial Degradation ◽  
Human Neutrophils ◽  
Gastrointestinal Disorders ◽  
Non Invasive

In the last years the need for a non-invasive diagnostic tool that would help to discriminate between organic and functional gastrointestinal disorders directed research towards potential immunological markers. A great number of non-invasive bio-markers has been proposed, including eosinophilic cationic protein, elastase, esterase, myeloperoxidase, lysozyme, lactoferrin, and calprotectin. Compared to other biomarkers, calprotectin (also called MRP8/14, calgranulin A/B , S100 A8/A9) may offer advantages based on its biological characteristics. Calprotectin is a 36.5-kDa, calcium and zinc binding polypeptide which constitutes about 60% of soluble cytosol proteins in human neutrophils. It is also found in monocytes, keratinocytes, muscle tissue and infiltrating tissue macrophages. When bound to calcium it becomes resistant to proteolysis and colonic bacterial degradation. This make is stable for up to 1 week at room temperature and facilitate its determination in feces. Calprotectin is involved in the regulation of the inflammatory process, participate to the early innate immune response and exert antimicrobial, anti-proliferative and apoptotic properties. Fecal calprotectin is a direct measure of mucosal inflammation activity and becomes detectable when intestinal inflammation is still at an insufficient level to cause an increase in serum inflammation markers. In the last decade fecal calprotectin has been proposed as a marker to rule out acute and chronic intestinal inflammatory diseases in children with typical gastrointestinal symptoms. Many studies demonstrated its diagnostic utility in identifying children and adults with inflammatory bowel disease and correlate with the degree of disease activity. The detection of elevated levels of fecal calprotectin in healthy infants during the first few weeks of age, limits their use as screening test for intestinal inflammatory diseases in early life. Despite this evidence, the measurement of calprotectin in the serum has been proposed to identify neonates with necrotizing enterocolitis. Recent studies have shown higher fecal calprotectin levels in infants with irritable bowel syndrome and colics, compared with healthy controls. Additionally, a correlation was found between fecal calprotectin concentration and IBS clinical presentation severity. However, these studies do not provide data on diagnostic accuracy in distinguish between organic and functional gastrointestinal disorders. Despite significant limitations, these evidences suggest the presence of a subtle inflammatory process underlying functional gastrointestinal disorders and open new perspectives on their pathogenesis. Fecal calprotectin may play a role that could be revealed in further, specifically designed, studies. Changes in microflora, permeability, calprotectin excretion and other inflammatory biomarkers, should be investigated to clarify if a continuum exists between inflammatory conditions and intestinal functional diseases.

scholarly journals Calprotectin as a marker of bowel inflammation

2013 ◽  
Author(s):  
Gianluca Terrin ◽  
Andrea Pietravalle
Keyword(s):  
Inflammatory Process ◽  
Intestinal Inflammation ◽  
Inflammatory Diseases ◽  
Functional Gastrointestinal Disorders ◽  
Gastrointestinal Symptoms ◽  
Fecal Calprotectin ◽  
Bacterial Degradation ◽  
Human Neutrophils ◽  
Gastrointestinal Disorders ◽  
Non Invasive

In the last years the need for a non-invasive diagnostic tool that would help to discriminate between organic and functional gastrointestinal disorders directed research towards potential immunological markers. A great number of non-invasive bio-markers has been proposed, including eosinophilic cationic protein, elastase, esterase, myeloperoxidase, lysozyme, lactoferrin, and calprotectin. Compared to other biomarkers, calprotectin (also called MRP8/14, calgranulin A/B , S100 A8/A9) may offer advantages based on its biological characteristics. Calprotectin is a 36.5-kDa, calcium and zinc binding polypeptide which constitutes about 60% of soluble cytosol proteins in human neutrophils. It is also found in monocytes, keratinocytes, muscle tissue and infiltrating tissue macrophages. When bound to calcium it becomes resistant to proteolysis and colonic bacterial degradation. This make is stable for up to 1 week at room temperature and facilitate its determination in feces. Calprotectin is involved in the regulation of the inflammatory process, participate to the early innate immune response and exert antimicrobial, anti-proliferative and apoptotic properties. Fecal calprotectin is a direct measure of mucosal inflammation activity and becomes detectable when intestinal inflammation is still at an insufficient level to cause an increase in serum inflammation markers. In the last decade fecal calprotectin has been proposed as a marker to rule out acute and chronic intestinal inflammatory diseases in children with typical gastrointestinal symptoms. Many studies demonstrated its diagnostic utility in identifying children and adults with inflammatory bowel disease and correlate with the degree of disease activity. The detection of elevated levels of fecal calprotectin in healthy infants during the first few weeks of age, limits their use as screening test for intestinal inflammatory diseases in early life. Despite this evidence, the measurement of calprotectin in the serum has been proposed to identify neonates with necrotizing enterocolitis. Recent studies have shown higher fecal calprotectin levels in infants with irritable bowel syndrome and colics, compared with healthy controls. Additionally, a correlation was found between fecal calprotectin concentration and IBS clinical presentation severity. However, these studies do not provide data on diagnostic accuracy in distinguish between organic and functional gastrointestinal disorders. Despite significant limitations, these evidences suggest the presence of a subtle inflammatory process underlying functional gastrointestinal disorders and open new perspectives on their pathogenesis. Fecal calprotectin may play a role that could be revealed in further, specifically designed, studies. Changes in microflora, permeability, calprotectin excretion and other inflammatory biomarkers, should be investigated to clarify if a continuum exists between inflammatory conditions and intestinal functional diseases.

scholarly journals The usefulness of fecal calprotectin testing in pediatric gastroenterology clinical practice

2020 ◽  
Author(s):  
Eliza Lężyk-Ciemniak ◽  
Magdalena Tworkiewicz ◽  
Dominika Wilczyńska ◽  
Anna Szaflarska-Popławska ◽  
Aneta Krogulska
Keyword(s):  
Gastrointestinal Tract ◽  
Intestinal Inflammation ◽  
Fecal Calprotectin ◽  
Diagnostic Methods ◽  
Delay In Diagnosis ◽  
Number Of Children ◽  
Non Invasive ◽  
Course Of Action ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Abstract Gastrointestinal tract symptoms such as abdominal pain, constipation, diarrhea, and fever are frequent causes of visits to the pediatrician. The increasing prevalence of chronic gastrointestinal tract diseases, and the falling median age of their onset, indicate the need to identify new diagnostic methods that can differentiate inflammatory bowel diseases from other gastrointestinal tract conditions. A promising non-invasive and useful marker of intestinal inflammation is fecal calprotectin. The manuscript summarizes currently available information on the use of fecal calprotectin in the diagnosis and monitoring of inflammatory bowel disease in children. It also attempts to determine the effect of concentration on its course of action. Incorporating fecal calprotectin (FC) testing within the framework of primary medical care can decrease the number of children unnecessarily referred for endoscopic or radiologic examination. FC screening benefits patients by reducing any delay in diagnosis and avoiding unnecessary exposure to endoscopy, and benefits physicians by reducing pressure on endoscopy testing and assisting the decision. The present paper emphasizes the role of fecal calprotectin as a non-invasive marker for monitoring disease activity and efficacy of therapy, and predicting postoperative relapses, primarily in patients with IBD.

Use of faecal immunochemical testing as an alternative to faecal calprotectin in children

2021 ◽  
pp. 000456322198935
Author(s):  
Kirn Sandhu ◽  
Sandhia Naik ◽  
Ruth M Ayling
Keyword(s):  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Paediatric Population ◽  
Mucosal Healing ◽  
Faecal Calprotectin ◽  
Non Invasive ◽  
Three Samples ◽  
Immunochemical Test ◽  
Inflammatory Bowel ◽  
Rule Out

Background Faecal calprotectin has been widely used as a non-invasive marker of intestinal inflammation in children. Measurement of faecal haemoglobin using faecal immunochemical test is well established in adults for detection of colorectal cancer. In adults, faecal haemoglobin has been recommended as a reliable tool to aid identification of those at low risk of significant bowel disease and has also been used in inflammatory bowel disease to assess mucosal healing. Aims We aimed to evaluate the performance of faecal haemoglobin in the paediatric population and compare it with faecal calprotectin. Methods Children being assessed in the paediatric gastroenterology clinic for bowel symptoms had a sample sent for both faecal calprotectin and faecal haemoglobin. Samples were collected over a 10-month period from November 2018 to September 2019. Faecal haemoglobin was measured using an OC-Sensor. Faecal calprotectin was measured using Liason®Calprotectin. Results One hundred forty three samples were returned for faecal haemoglobin and in 107 a paired faecal calprotectin was also available. Faecal haemoglobin correlated with faecal calprotectin, Spearman’s rank coefficient 0.656 ( P < 0.0001). There were 35 patients with faecal haemoglobin >20 μg/g and in 32 of these patients faecal calprotectin was >200 μg/g; 74 patients with faecal haemoglobin and 38 patients with faecal calprotectin underwent colonoscopy. Patients with normal histology had faecal haemoglobin <4 μg/g; faecal haemoglobin >20 µg/g was associated with signification inflammation Conclusion Our study is the first to compare faecal haemoglobin and faecal calprotectin in a paediatric population. Results suggest that faecal haemoglobin correlates with faecal calprotectin and, as in adults, may be useful to rule out significant bowel disease. A faecal haemoglobin >20 μg/g was consistent with significant histological inflammation.

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