Calprotectin Concentration In Patients Research Articles

Urinary calprotectin as a diagnostic tool for detecting significant bacteriuria

Pyuria in dipstick examination serves as the most widespread screening tool for urinary tract infections (UTI). The absence of pyuria, however, does not exclude UTI. We investigated the diagnostic value of urinary calprotectin, a mediator protein of the innate immune system, which is released by leukocytes, for the detection of UTI and compared it with dipstick pyuria. Since even low numbers of leukocytes in the urine significantly increase urinary calprotectin concentrations, calprotectin might be a more sensitive marker than pyuria detected by dipstick. All 162 patients were prospectively included and underwent a urine dipstick, urine culture, quantification of proteinuria and determination of calprotectin in the urine. Urinary calprotectin was determined using an enzyme-linked immunosorbent assay (ELISA). UTI was defined as urine cultures with detection of one or a maximum of two uropathogenic bacteria with ≥ 105 colony-forming units per millilitre (CFU/ml). Exclusion criteria were acute kidney injury, chronic renal insufficiency and tumors of the urinary tract. 71 (43.8%) patients had a UTI. Of the 91 patients without UTI, 23 had a contamination and 19 had evidence of ≥ 105 CFU/ml considered to be asymptomatic bacteriuria. The median calprotectin concentration in patients with UTI and pyuria was significantly higher than in patients with UTI and without pyuria (5510.4 vs. 544.7 ng/ml). In ROC analyses, calprotectin revealed an area under the curve (AUC) of 0.70 for the detection of significant bacteriuria. Pyuria in dipstick examinations provided an AUC of 0.71. There was no significant difference between these AUCs in the DeLong test (p = 0.9). In patients with evidence of significant bacteriuria but without pyuria, a significantly higher calprotectin concentration was measured in the urine than in patients with neither pyuria nor UTI (544.7 ng/ml vs 95.6 ng/ml, p = 0.029). Urinary calprotectin is non-inferior to dipstick pyuria in the detection of UTI.

Plasma calprotectin is extremely high in patients with lysinuric protein intolerance.

Lysinuric protein intolerance (LPI) is a rare autosomal recessive disorder affecting the transport of cationic amino acids. Elevated plasma zinc concentrations have been described in patients with LPI. Calprotectin is a calcium- and zinc-binding protein, produced by polymorphonuclear leukocytes and monocytes. Both zinc and calprotectin have an important role in immune system. In this study, we describe plasma zinc and plasma calprotectin concentrations in Finnish LPI patients. Plasma calprotectin concentration was measured from 10 LPI patients using an enzyme-linked immunosorbent assay (ELISA) and it was remarkably high in all LPI patients (median: 622 338 μg/L) compared to that in healthy controls (608 μg/L). Plasma zinc concentration was measured by photometry and it was normal or only mildly elevated (median: 14.9 μmol/L). All the patients had decreased glomerular infiltration rate (median: 50 mL/min/1.73 m2). In conclusion, we observed extremely high plasma calprotectin concentration in patients with LPI. Mechanism of this phenomenon is unknown.

Circulating calprotectin as a biomarker of laryngeal carcinoma.

Calprotectin is an S100 protein and marker of inflammation found in neutrophils and monocytes; S100 proteins are a family of calcium-modulated proteins. The aim of this study was to determine if the serum concentration of calprotectin is higher in patients with laryngeal carcinoma than in patients with benign laryngeal pathologies and controls. The study included 107 participants. The serum calprotectin concentration was analyzed using the calprotectin ELISA (enzyme-linked immunosorbent assay) kit (Calpo AS, Norway). EDTA-serum for analysis was collected prior to surgery from patients with laryngeal carcinoma (n = 41), those with a benign laryngeal pathology (Reinke's edema, vocal nodules, etc.) (n = 32), and healthy controls (n = 34). The median serum calprotectin concentration was significantly higher in the laryngeal carcinoma group (2179.6μgL-1) than in the benign laryngeal pathology group (727.84μgL-1) and control group (733.73μgL-1) (P < 0.05). The median serum calprotectin concentration in patients with advanced-stage laryngeal cancer (5854.,4μgL-1) was significantly higher than in those with early-stage laryngeal cancer (971.84μgL-1) (P < 0.05); however, there was not a significant difference in the median calprotectin concentration between the control and benign laryngeal pathology groups (P > 0.05). Furthermore, the median serum calprotectin concentration in the patients with early-stage laryngeal cancer (n = 21) (971.84μgL-1) was significantly higher than that in the benign laryngeal pathology and control groups (n = 64) (730.6μgL-1) (P < 0.05). The serum calprotectin concentration was strongly correlated with poor survival and advanced-stage laryngeal carcinoma. Malignant laryngeal cancer patients (n = 4) that died during follow-up had a higher median serum calprotectin concentration (9468.4μgL-1) than those that remained alive (n = 37) (857.78μgL-1) (P < 0.05). The serum calprotectin concentration is higher in patients with laryngeal carcinoma than in those with benign laryngeal pathologies and healthy controls. The present findings show that the serum calprotectin concentration might be used as a marker to discriminate between laryngeal carcinoma and benign laryngeal pathologies. Additional research is needed to further assess the value of this parameter as a useful tumor marker for the diagnosis, treatment, and follow-up of laryngeal carcinoma.

Serum calprotectin--a promising diagnostic marker for adult-onset Still's disease.

Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still’s disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjögren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 ± 18.00 ng/ml), compared to patients with RA (39.17 ± 18.90 ng/ml), pSS (35.31 ± 19.47 ng/ml), SLE (32.21 ± 25.01 ng/ml), OA (19.24 ± 10.67 ng/ml), and HCs (8.46 ± 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1 %, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin-positive patients compared to negative patients in AOSD (103.49 ± 20.21 g/l vs 115.71 ± 15.59 g/l, t = −2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent.

Serum Calprotectin as a Marker for Disease Activity and Severity in Adult-onset Still’s Disease

Calprotectin is a calcium-binding cytosolic protein of the neutrophil, monocyte, and macrophage, and its secretion increases during activation of these cells. Our objective was to measure serum calprotectin concentrations in patients with adult-onset Still's disease (AOSD) and to correlate serum calprotectin with the activity and severity of AOSD. We enrolled 25 patients with AOSD and 30 age- and sex-matched healthy controls. Thirty-one serum samples were obtained from patients with AOSD during active or inactive disease and were assayed for calprotectin by ELISA. Clinical and laboratory data related to disease activity and severity were collected at the same time, and systemic scores for disease severity were calculated. Mean calprotectin levels in patients with AOSD were significantly higher than in controls (57.11 +/- 25.38 ng/ml vs 34.90 +/- 4.85 ng/ml, respectively; p < 0.05). Patients with active AOSD had a significantly higher mean calprotectin level than those with inactive disease (61.26 +/- 25.59 ng/ml vs 35.32 +/- 5.90 ng/ml; p < 0.05). Calprotectin levels decreased significantly after treatment in all 6 patients with AOSD from whom followup samples were obtained (p = 0.028). Serum calprotectin showed strong correlations with serum ferritin (r = 0.686, p < 0.001), lactate dehydrogenase (r = 0.647, p < 0.001), leukocyte count (r = 0.774, p < 0.001), aspartate aminotransferase (r = 0.387, p = 0.042), and C-reactive protein (r = 0.588, p = 0.001), but not with erythrocyte sedimentation rate, arginine aminotransferase, hemoglobin, or platelet count. Serum calprotectin showed a significant correlation with AOSD systemic scores, reflecting disease severity (r = 0.803, p < 0.001). Serum calprotectin increased in patients with AOSD, in close correlation with disease activity and severity. These findings suggest that serum calprotectin can provide a reliable clinical marker for monitoring the disease activity and severity of AOSD.

Fecal calprotectin and lactoferrin for the prediction of inflammatory bowel disease relapse

The purpose of the study was to determine the role of fecal calprotectin and lactoferrin in the prediction of inflammatory bowel disease relapses, both in patients with ulcerative colitis (UC) and Crohn's disease (CD), in a large, long-term, follow-up study. The prospective multicenter study included CD and UC patients who had been in clinical remission for 6 months. At baseline, patients provided a single stool sample for calprotectin and lactoferrin determination. Follow-up was 12 months in patients showing no relapse and until activity flare in relapsing patients. In all, 163 patients (89 CD, 74 UC) were included. Twenty-six patients (16%) relapsed during follow-up. Calprotectin concentrations in patients who suffered a relapse were higher than in nonrelapsing patients (239 +/- 150 versus 136 +/- 158 microg/g; P < 0.001). Relapse risk was higher in patients having high (>150 microg/g) calprotectin concentrations (30% versus 7.8%; P < 0.001) or positive lactoferrin (25% versus 10%; P < 0.05). Fecal calprotectin (>150 microg/g) sensitivity and specificity to predict relapse were 69% and 69%, respectively. Corresponding values for lactoferrin were 62% and 65%, respectively. The area under the receiver operating characteristic curve to predict relapse using calprotectin determination was 0.73 (0.69 for UC and 0.77 for CD). Better results were obtained when only colonic CD disease or only relapses during the first 3 months were considered (100% sensitivity). High fecal calprotectin levels or lactoferrin positivity was associated with clinical relapse in Kaplan-Meier survival analysis, and both fecal tests were associated with relapse in the multivariate analysis. Fecal calprotectin and lactoferrin determination may be useful in predicting impending clinical relapse-especially during the following 3 months-in both CD and UC patients.

Clinical utility of the assessment of fecal calprotectin in Leśniowski‑Crohn’s disease

From the epidemiological point of view, Leśniowski-Crohn's disease (CD) has become an important medical problem. It is essential to differentiate CD from functional disorders of the gastrointestinal tract, first of all, from irritable bowel syndrome (IBS). There are no simple, non-invasive tests available which could help to identify patients with common symptoms such as abdominal pain or diarrhea who should be referred for further evaluation, including endoscopy. The aim of this study was to evaluate the diagnostic utility of the assessment of fecal calprotectin concentration in patients with CD. Stool samples were taken from 31 patients of the Gastroenterology, Human Nutrition and Internal Diseases Department of Poznań Medical University who were diagnosed with CD. Patients suffering from IBS served as the control group. Calprotectin concentration was assessed by means of the immunoenzymatic ELISA method. Serum C-reactive protein (CRP) concentration and blood cell count were determined. The clinical activity of CD was assessed by means of Crohn's Disease Activity Index. An appropriate statistical analysis was performed. Mean calprotectin concentration in CD group was 32.01 +/- 22.58 mg/l and it was statistically higher (p <0.0003) than among IBS patients. A concentration of 16.01 mg/l had 67.7% sensitivity and 66.7% specificity in distinguishing between CD and IBS. There was a positive correlation between calprotectin concentration and CRP, and negative--with hemoglobin concentration. The assessment of fecal calprotectin concentration may be useful in differential diagnoses of CD and monitoring patients with CD.

Fecal Calprotectin Concentrations in Patients with Small Intestinal Bacterial Overgrowth

Background/Aims: Small intestinal bacterial overgrowth (SIBO) is defined by any condition in which the proximal part of the small bowel harbors for a long time >10⁵ bacteria/ml of the intestinal juice. No data are currently available about direct or indirect parameters indicating the presence of leukocytes in the gut wall and mucosal neutrophil turnover in patients with SIBO. In our pilot study we evaluate fecal calprotectin concentrations (FCC) in patients with SIBO in order to identify a possible presence of subclinical intestinal inflammation. Methods: 40 consecutive patients with SIBO resulting positive to hydrogen glucose breath test, and 40 adult healthy volunteers were included in the study. FCC were determined by ELISA. Mean FCC were compared by means of the t-test for independent samples. Results: FCC in patients with SIBO were not significantly different compared to controls (p = 0.907). Conclusion: Our study shows for the first time that FCC in patients with SIBO do not significantly differ from controls, suggesting that in SIBO there are no intestinal subclinical inflammatory changes involving principally the neutrophils.

Prophylactic aspirin therapy does not increase faecal calprotectin concentrations

Non-steroidal anti-inflammatory drugs (NSAID) can induce enteropathy. Aspirin ingestion is associated with a lower small-intestinal inflammation than other NSAID. Faecal calprotectin concentrations have recently been proposed as a simple non-invasive test to identify NSAID enteropathy. The aim of our pilot study was to evaluate calprotectin concentrations in patients on treatment with low-dose aspirin. Twenty-two patients on prophylactic treatment with aspirin were recruited. Twenty-five healthy volunteers were enrolled as a control group. Faecal calprotectin concentrations were determined by enzyme-linked immunosorbent assay. Statistical analysis was performed by t-test for unpaired data. The mean faecal calprotectin concentration in patients (57.95+/-44.28 microg/g) did not show significant differences compared with controls (45.76+/-26.45 microg/g; P=0.251). We found that low-dose aspirin does not induce an increase in faecal calprotectin increase.

This month in gastroenterology

This month in gastroenterology

Subclinical intestinal inflammation: an inherited abnormality in Crohn’s disease relatives?

Background & aims: One approach to unraveling the genetics of complex inherited disease, such as Crohn’s disease, is to search for subclinical disease markers among unaffected family members. We assessed the possible presence, prevalence, and inheritance pattern of subclinical intestinal inflammation in apparently healthy relatives of patients with Crohn’s disease. Methods: A total of 49 patients with Crohn’s disease, 16 spouses, and 151 (58%) of 260 available first-degree relatives underwent a test for intestinal inflammation (fecal calprotectin concentration). The mode of inheritance was assessed from 36 index patients (by variance component analysis) when more than 50% of relatives were studied. Results: Fecal calprotectin concentrations in patients with Crohn’s disease (47 mg/L; confidence interval [CI], 27–95 mg/L) and relatives (11 mg/L; CI, 9–14 mg/L) differed significantly ( P < 0.0001) from controls (4 mg/L; CI, 3–5 mg/L), whereas that of the spouses did not (4 mg/L; CI, 3–6 mg/L; P > 0.5). Fecal calprotectin concentration was increased in 49% of all relatives studied. The increased fecal calprotectin concentration among the relatives of the 36 index patients had an inheritance pattern that was most consistent with an additive inheritance pattern. Conclusions: There is a high prevalence of subclinical intestinal inflammation in first-degree relatives of patients with Crohn’s disease that conforms best to an additive inheritance pattern. The genetic basis for this abnormality may represent a risk factor for Crohn’s disease.

Fecal calprotectin as an index of intestinal inflammation.

The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques, from measurement of conventional noninvasive acute-phase inflammatory markers in plasma (C-reactive protein and the erythrocyte sedimentation rate) to the direct assessment of disease activity by intestinal biopsy. However, most of these techniques have significant limitations when it comes to assessing functional components of the disease that relate to activity and prognosis. Here we briefly review the value of a novel emerging intestinal function test, fecal calprotectin. Single stool assay of neutrophil-specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4-day fecal excretion of indium-111-labeled white cells. Elevated levels of fecal calprotectin have been demonstrated in patients with NSAID-induced enteropathy and have been used in the diagnosis of colorectal cancer. Fecal calprotectin is increased in over 95% of patients with inflammatory bowel disease (IBD) and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome (IBS). More importantly, at a given fecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated. (c) 2001 Prous Science. All rights reserved.

Non-invasive investigation of inflammatory bowel disease.

The assessment of inflammatory activity in intestinal disease in man can be done using a variety of different techniques. These range from the use of non-invasive acute phase inflammatory markers measured in plasma such as C reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) (both of which give an indirect assessment of disease activity) to the direct assessment of disease activity by intestinal biopsy performed during endoscopy in association with endoscopic scoring systems. Both radiology and endoscopy are conventional for the diagnosis of inflammatory bowel disease (IBD). However these techniques have severe limitations when it comes to assessing functional components of the disease such as activity and prognosis. Here we briefly review the value of two emerging intestinal function tests. Intestinal permeability, although ideally suited for diagnostic screening for small bowel Crohn's disease, appears to give reliable predictive data for imminent relapse of small bowel Crohn's disease and it can be used to assess responses to treatment. More significantly it is now clear that single stool assay of neutrophil specific proteins (calprotectin, lactoferrin) give the same quantitative data on intestinal inflammation as the 4 day faecal excretion of 111Indium labelled white cells. Faecal calprotectin is shown to be increased in over 95% of patients with IBD and correlates with clinical disease activity. It reliably differentiates between patients with IBD and irritable bowel syndrome. More importantly, at a given faecal calprotectin concentration in patients with quiescent IBD, the test has a specificity and sensitivity in excess of 85% in predicting clinical relapse of disease. This suggests that relapse of IBD is closely related to the degree of intestinal inflammation and suggests that targeted treatment at an asymptomatic stage of the disease may be indicated.

Fecal calprotectin concentration in patients with colorectal carcinoma.

The study contained herein was undertaken to investigate fecal calprotectin excretion in a series of patients with colorectal carcinoma and to determine whether the excretion was influenced by localization or stage of the tumor. Furthermore, the effect of surgical treatment on the concentrations was studied. Fecal calprotectin was also compared with plasma concentrations of calprotectin, carcinoembryonic antigen, and C-reactive protein. Fecal calprotectin was measured in 119 consecutive patients admitted for treatment of colorectal carcinoma. In 116 (97.5 percent) patients, resectional surgery was performed. Plasma calprotectin was measured in 90 (76 percent) patients, carcinoembryonic antigen in 88 (74 percent) patients, and C-reactive protein in 82 (69 percent) patients. Median fecal calprotectin concentration in the 119 patients was 50 (range, 2-950) mg/l, which was significantly (P < 0.0001) higher than in 125 control patients (median, 5.2 mg/l). In 23 patients studied also after resection, the excretion fell greatly. There were no significant differences in fecal calprotectin concentration among patients with different tumor stages. Elevated plasma calprotectin concentrations were found in 67 of 90 (73.3 percent) patients with colorectal carcinoma, compared with elevated fecal calprotectin in 111 of 119 (93.3 percent) patients, and there was no significant correlation between plasma and fecal calprotectin concentrations. Plasma calprotectin concentrations were significantly lower in patients with T1 or T2 tumors than in those with more advanced stages (P = 0.0025). Measurement of fecal calprotectin may become a diagnostic tool in detecting colorectal carcinoma. The specificity in relation to colorectal carcinoma has not, however, been completely investigated. Both neoplastic and inflammatory conditions may be associated with elevated values; therefore, it is unlikely that calprotectin can predict specific colonic disorders.