Calprotectin Concentrations Research Articles

Zinc-binding metallophores protect Pseudomonas aeruginosa from calprotectin-mediated metal starvation.

Pseudomonas aeruginosa is known to exhibit considerable resistance to the antimicrobial activity of the metal-sequestering protein calprotectin (CP). In this study, we demonstrate that although CP induces zinc deficiency in P. aeruginosa, a strain unable to import zinc through the two most important metal acquisition systems, namely ZnuABC and ZrmABCD, maintains significant growth capacity in the presence of high concentrations of CP. Furthermore, we have shown that nicotianamine, a molecule structurally similar to the metallophore pseudopaline, can favor the acquisition of the metal even in the presence of CP. To gain insights into the mechanisms through which metallophores can promote zinc acquisition, we analyzed the effect of nicotianamine on the activity of the metallo-β-lactamase VIM-1. Our data suggest that metallophores released by bacteria in response to zinc deficiency can extract the protein-bound metal. The ability to interfere with the binding of metals to proteins, as well as favoring the acquisition of zinc, may contribute to increasing the resistance of P. aeruginosa to the antimicrobial action of CP.

Verification of the fCAL turbo immunoturbidimetric assay for measurement of the fecal calprotectin concentration in dogs and cats.

The concentration of calprotectin in feces (fCal) is a clinically useful marker of chronic gastrointestinal inflammation in humans and dogs. No commercial assay is widely available to measure fCal in small animal medicine, to date. Thus, we verified the immunoturbidimetric fCAL turbo assay (Bühlmann) of fCal for canine and feline fecal extracts by determining linearity, spiking and recovery, and intra-assay and inter-assay variability. We determined RIs, temporal variation over 3 mo, and effect of vaccination and NSAID treatment. Observed:expected (O:E) ratios (x̄ ± SD) for serial dilutions of feces were 89–131% (106 ± 9%) in dogs and 77–122% (100 ± 12%) in cats. For spiking and recovery, the O:E ratios were 90–118% (102 ± 11%) in dogs and 83–235% (129 ± 42%) in cats. Intra- and inter-assay CVs for canine samples were ≤19% and ≤7%, and for feline samples ≤22% and ≤21%. Single-sample RIs were <41 μg/g for dogs and <64 μg/g for cats. With low reciprocal individuality indices, using population-based fCal RIs is appropriate, and moderate fCal changes between measurements (dogs 44.0%; cats: 43.2%) are considered relevant. Cats had significant (but unlikely relevant) fCal increases post-vaccination. Despite individual fCal spikes, no differences were seen during NSAID treatment. The fCAL turbidimetric assay is linear, precise, reproducible, and sufficiently accurate for measuring fCal in dogs and cats. Careful interpretation of fCal concentrations is warranted in both species during the peri-vaccination period and for some patients receiving NSAID treatment.

Impact of Preanalytical Factors on Calprotectin Concentration in Stool: A Multiassay Comparison.

Measuring calprotectin concentration in stool is increasingly important in monitoring disease activity and treatment response in inflammatory bowel disease. This study evaluates the impact of preanalytical storage conditions on reliability of calprotectin testing using 5 different calprotectin immunoassays. Aliquots of homogenized fresh fecal samples in untreated or extracted form were stored at room temperature or 4°C. Calprotectin concentration was measured day 0 to 4 and 8. Five different immunoassays and accompanying extraction buffers were used (CALiaGold, Phadia EliA, Bühlmann fCal turbo, ELISA Bühlmann, Inova Quanta Flash). Repeated measurements of change from baseline calprotectin levels over time were analyzed using a mixed model analysis. Calprotectin concentrations declined over time under all preanalytical conditions with all assays, except for extracted feces stored at 4°C. The rate of decline was greatest in untreated stool kept at room temperature, reaching significant difference from baseline already after 1 day (P &lt; 0.001). In extracted feces kept at room temperature, significant difference from baseline was reached after 2 days, and in untreated feces at 4°C, after 4 days. However, the results differed significantly between assays. After 4 days of storage at room temperature, the mean calprotectin decline from baseline differed between 30% and 60%, dependent on the assay used. Fecal calprotectin concentration in stool samples declines over time, and the rate of decline is greater at higher temperatures. In extracted feces stored at 4°C, calprotectin is most stable. It is assay-dependent how long extracted feces stored at 4°C give reliable test results.

Plasma calprotectin – preanalytical stability and interference from hemolysis

As an activation product of neutrophil granulocytes, calprotectin has been widely used in fecal samples for diagnosis and monitoring of patients with inflammatory bowel disease. However, fecal sample collection is cumbersome, and pre-analytical sources of error are plentiful. Therefore, plasma calprotectin is being investigated as a promising new biomarker. To utilize any biomarker, pre-analytical factors such as stability and susceptibility to interference from hemolysis must be established. We present precision estimates, stability results as well as interference study on plasma calprotectin in EDTA-plasma using the Thermo Fischer Phadia 250 EliATM Calprotectin immunoassay. Precision was estimated by the use of patient pools as well as internal quality controls provided by the manufacturer. Coefficients of variance were below 6.9% for patient samples. Calprotectin was stable in EDTA plasma after storage at 5–8 °C for up to 4 days, as well as after long-term storage at −20 °C. Susceptibility to interference from hemolysis was high, especially for low concentrations of calprotectin (<50 ng/mL) where hemoglobin levels above 0.02 mmol/L lead to false increase in calprotectin concentrations of up to 100%.

Keratinocyte-derived S100A9 modulates neutrophil infiltration and affects psoriasis-like skin and joint disease

ObjectivesS100A9, an alarmin that can form calprotectin (CP) heterodimers with S100A8, is mainly produced by keratinocytes and innate immune cells. The contribution of keratinocyte-derived S100A9 to psoriasis (Ps) and psoriatic...

Calprotectin may be positively associated with the severity of acne vulgaris

Background and objective: Acne vulgaris (AV) is a common skin disease of sebaceous hair follicles. Many factors are associated with the occurrence and severity of acne, while the exact etiology remains incompletely understood. The current study was aimed to investigate the association between the severity of acne and serum zinc, copper, and calprotectin. Methods: Fifty patients with AV were recruited in the study as well as 25 healthy age and sex-matched individuals as controls. The acne severity was classified into mild (n=21), moderate (n=16), and severe acne (n=14) according to the global acne grading system (GAGS). Serum levels of zinc, acne and calprotectin were evaluated by enzyme-linked immunosorbent assay (ELISA). The gained data were analyzed using GraphPad Prism software. Results: Insignificant difference was found in zinc and copper levels between controls and AV patients, except in severe AV, where the patients displayed significant elevation in serum copper level (p&lt;0.05) as compared to that of mild AV. The calprotectin concentration was significantly higher (p&lt;0.001) in all AV patients, when compared with healthy subjects, which was positively correlated with the disease severity. No gender difference was noted for all measured biomarkers. Conclusions: Our study suggests a possible association between calprotectin and acne inflammation, which requires validation in large-scale studies.

Understanding anti-TNF treatment failure: does serum triiodothyronine-to-thyroxine (T3/T4) ratio predict therapeutic outcome to anti-TNF therapies in biologic-naïve patients with active luminal Crohn's disease?

SummaryBackgroundDuring illness, adaptations of the hypothalamic–pituitary‐thyroid axis reduce energy expenditure, protein catabolism and modulate immune responses to promote survival. Lower serum free triiodothyronine‐to‐thyroxine (fT3/fT4) ratio has been linked to non‐response to treatment in a range of diseases, including in biologic‐treated patients with inflammatory bowel disease.AimTo assess whether baseline serum fT3/fT4 ratio predicted primary non‐response (PNR) and non‐remission to infliximab and adalimumab in patients with Crohn's diseaseMethodsThyroid function tests were undertaken in stored serum from biologic‐naïve adult patients with active luminal Crohn's disease immediately prior to treatment with infliximab (427 originator; 122 biosimilar) or adalimumab (448) in the Personalised Anti‐TNF Therapy in Crohn's Disease study (PANTS).ResultsBaseline median [IQR] fT3/fT4 ratios were lower in women than men (0.30 [0.27–0.34] vs 0.32 [0.28–0.36], p < 0.001), in patients with more severe inflammatory disease, and in patients receiving corticosteroids (0.28 [0.25–0.33] vs. 0.32 [0.29–0.36], p < 0.001). Multivariable logistic regression analysis demonstrated that fT3/fT4 ratio was independently associated with PNR at week 14 (odds ratio [OR] 0.51, 95% confidence interval [CI] 0.31–0.85, p = 0.009), but not non‐remission or changes in faecal calprotectin concentrations at week 54. The optimal threshold to determine PNR was 0.31 (area under the curve 0.57 [95% CI 0.54–0.61], sensitivity 0.62 [95% CI 0.41–0.74], and specificity 0.53 [95% CI 0.42–0.73]).ConclusionsLower baseline serum fT3/fT4 ratio was associated with female sex, corticosteroid use and disease activity. It predicted PNR to anti‐TNF treatment at week 14, but not non‐remission at week 54.

Serum Calprotectin - a NET Product - as a Biomarker of Disease Activity in Patients with Systemic Lupus Erythematosus: A Single-Center Case-Control Study from Poland.

BackgroundCalprotectin (S100A8/A9 or myeloid-related protein 8/14) is a heterodimeric S100 complex expressed in leukocytes. Calprotectin participates in development of the inflammatory response by binding to receptors for advanced glycation end-products (RAGE) and Toll-like receptors (TLR). The clinical activity of systemic lupus erythematosus (SLE) is evaluated using the Systemic Lupus International Collaborating Clinics (SLICC) criteria and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). This Polish single-center case-control study aimed to evaluate serum levels of calprotectin as a rapid diagnostic biomarker of SLE (59 patients with SLE were compared with 52 healthy controls).Material/MethodsCalprotectin concentration was measured with the use of enzyme-linked immunosorbent assay (ELISA). The SLE activity of the patients was assessed by the SLEDAI scale. Statistical analysis of the results was carried out using MedCalc 15.8 software. P<0.05 was considered statistically significant.ResultsA significantly higher concentration of calprotectin was found in the study group compared to the control group (medians: 3.11 vs 2.45 ng/ml; P=0.0013). We found that calprotectin has high sensitivity (89.83%) and specificity (53.85%) in differentiating between SLE patients and healthy volunteers. We found that calprotectin has very high sensitivity (100%) and specificity (82.46%) in detection of patients with moderate and severe SLE assessed using SLEDAI.ConclusionsConsistent with previous studies, serum calprotectin level was revealed to have potential as a rapid diagnostic biomarker of disease activity in patients with SLE.

The Effect of Nutritional Intervention with Lactoferrin, Galactooligosacharides and Vitamin D on the Gut Microbiota Composition of Healthy Elderly Women.

Background: Nutritional supplements, such as bovine lactoferrin (bLF), have been studied for their immunomodulatory properties, but little is known of their effect on the gut microbiota composition of the elderly when supplemented alone or combined with other nutritional supplements such as prebiotics and micronutrients. In the present study, fecal samples from a double-blind, placebo-controlled nutritional intervention study were analysed. At baseline (T1), 25 elderly women were distributed into two groups receiving dietary intervention (n = 12) or placebo treatment (n = 13) for 9 weeks. During the first 3 weeks of the study (T2), the intervention group consumed 1 g/day bLF, followed by 3 weeks (T3) of 1 g/day bLF and 2.64 g/day active galactooligosaccharides (GOS), and 3 weeks (T4) of 1 g/day bLF, 2.64 g/day GOS and 20 μg/day of vitamin D. The placebo group received maltodextrin, in dosages matching those of the intervention group. Fecal bacterial composition was profiled using partial 16S rRNA gene amplicon sequencing. Short-chain fatty acids (SCFA) were determined in fecal water as were levels of calprotectin, zonulin, and alpha-1-antitrypsin, as markers of gastrointestinal barrier and inflammation. Results: A significant increase was observed in the relative abundance of the genus Holdemanella (p < 0.01) in the intervention group compared to the placebo at T1. During T2, Bifidobacterium relative abundance increased significantly (p < 0.01) in the intervention group compared to the placebo, and remained significantly higher until the end of the study. No other effect was reported during T3. Furthermore, concentrations of SCFAs and calprotectin, zonulin and alpha-1-antitrypsin did not change during the intervention, although zonulin levels increased significantly within the placebo group by the end of the intervention. Conclusions: We conclude that supplementation of bLF enhanced the relative abundance of Holdemanella in the fecal microbiota of healthy elderly women, and further addition of GOS enhanced the relative abundance of Bifidobacterium.

Predictive value of faecal calprotectin in ulcerative colitis – single centre experience

Objectives Faecal calprotectin is an important biomarker used in the evaluation of inflammatory bowel disease. The aim of this study was to establish the value of faecal calprotectin concentration as a predictor of remission in ulcerative colitis and its correlation with laboratory, endoscopic and clinical findings. Methods The single centre study included 126 adult patients with established diagnosis of ulcerative colitis consecutively visiting our Day clinic from March 2017 to March 2019. We measured serum biomarkers- CRP, haemoglobin, leukocytes and platelets. Faecal calprotectin was determined from stool, and endoscopy was performed with calculation of MAYO endoscopic subscore system (MES 0–1: remission, and MES 2–3: active disease). Clinical assessment was done by using Mayo score for ulcerative colitis (clinical Mayo score <2:remission, >5: active disease).The statistical analysis was performed using an univariate and multivariate model of disease remission prediction using logistic regression. Results According to univariate analysis the increase of faecal calprotectin concentration by 10 ug/g is associated with an 8% decrease in probability of disease remission (OR 0.9921, p < .05). In the multivariate analysis, faecal calprotectin remained a significant predictor of disease remission (OR 0.9948, 95% CI 0.9914–0.9982, p = .0028), however, with a significant contribution of C-reactive protein (OR 0.8340, 95% CI 0.7085–0.9818, p = .0292). According to our model the cut off value for faecal calprotectin was 154 ug/g. Conclusion Our results have shown that faecal calprotectin is an independent predictor of remission in UC patients. The results of our study represent real-life data from a single university centre dealing with FC as a prognostic marker in patients with UC. KEY MESSAGES Faecal calprotectin is an independent predictor of remission in UC patients. Recent studies have suggested that calprotectin correlates well with endoscopic activity of inflammation but correlation of faecal calprotectin in a phase of remission hasn’t been evaluated yet. We have found that other inflammatory biomarkers do not correlate well with either endoscopic or clinical activity in ulcerative colitis.

MO308: Urinary Biomarkers to Predict Acute Kidney Damage and Mortality In COVID-19

BACKGROUND AND AIMSAcute kidney injury (AK) is a frequent condition in patients hospitalized for COVID-19. There are only few reports on the use of urinary biomarkers in COVID-19 and no data comparing the prognostic use of individual biomarkers in the prediction of adverse outcome so far.METHODWe performed a prospective monocentric study on the value of urinary biomarkers to predict the composite endpoint of a transfer to the intensive care unit (ICU), the need for renal replacement therapy (RRT), mechanical ventilation and in-hospital mortality. A total of 41 patients hospitalized for COVID-19 were enrolled in this study. Urine samples were obtained shortly after admission in order to assess neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), calprotectin and vanin-1.RESULTSWe identified calprotectin as a predictor of a severe course of the disease, requiring intensive care treatment (AUC 0.728, P = .016). Positive and negative predictive values were 78.6% and 76.9%, respectively, using a cut-off concentration of 127.8 ng/mL. NGAL tended to predict COVID-19 associated AKI without reaching statistical significance (AUC 0.669, P = .053). The best parameter in the prediction of in-hospital mortality was NGAL as well (AUC 0.674, P = .077). KIM-1 and vanin-1 did not reach significance for any of the investigated endpoints.CONCLUSIONWhile KIM-1 and vanin-1 did not provide prognostic clinical information in the context of COVID-19, this study shows that urinary calprotectin and NGAL concentrations are independent predictors of an adverse course of the disease. Calprotectin and NGAL may thereby constitute helpful adjuncts in the identification of patients at increased risk who may benefit from upcoming antiviral agents to SARS-CoV-2.

Influence of Rectal Ozone Application on the Intensity of Free Radical Destruction of Lipids and Intestinal Proteins in the Dynamics of Experimental Colitis.

We studied clinical status, content of products of LPO, and oxidative modification of proteins (OMP) in the lesion focus of the intestine in experimental colitis under conditions of rectal administration of ozone. Experimental colitis was simulated by two-stage administration of oxazolone; rectal insufflation of ozone in the ozone-oxygen mixture was performed daily. The disease activity index (DAI), the content of calprotectin in the feces, and LPO and OMP products in the intestinal homogenate were assessed. On days 2, 4, and 6 of the pathological process, DAI, concentration of calprotectin in feces, content of primary, secondary, and end-products of LPO in the heptane and isopropanol phases, and content of primary and secondary OMP products progressively increases. Under conditions of ozone application, DAI, concentration of calprotectin in feces, the levels of heptane- and isopropanol-soluble primary, secondary, and end-products of LPO, and the level of primary and secondary products of OMP decreased on days 4 and 6; the level of isopropanol-soluble primary, secondary, end-products of LPO increased on day 2 of experimental colitis. The severity of clinical manifestations weakens as the content of LPO and OMP products in the colon decreases on days 4 and 6 of observation.

Associations among serum insulin, calprotectin, and C-reactive protein concentrations in Miniature Schnauzers with idiopathic hyperlipidemia before and after feeding an ultra-low-fat diet.

BackgroundMiniature Schnauzers (MS) commonly have idiopathic hypertriglyceridemia (HTGL), which is associated with insulin resistance (IR) and a subclinical inflammatory phenotype.ObjectivesDetermine the association between indicators of IR and inflammatory biomarkers in MS with and without HTGL and identify how indicators of IR are affected by dietary intervention in MS with HTGL.AnimalsSeventy MS with HTGL and 79 MS without HTGL. In addition, 15 MS with HTGL were placed on a low‐fat diet.MethodsSerum concentrations of triglycerides, cholesterol, calprotectin, insulin, and glucose were compared between groups.ResultsSerum glucose and calprotectin concentrations (shown to be higher in MS with HTGL than in MS without HTGL) were inversely correlated (ρ = −.28; P < .001). After dietary intervention, median serum insulin concentrations were 8.1 mU/L compared to 20.8 mU/L before dietary intervention (P = .06). Dogs with complete resolution of HTGL after dietary intervention (5 dogs) had significantly lower serum insulin concentrations compared to baseline (P = .03).Conclusion and Clinical ImportanceThe subclinical inflammatory phenotype in MS with HTGL appears to be associated with IR. Resolution of HTGL by dietary intervention is associated with a decrease in serum insulin concentrations. The implication of the increase in serum calprotectin concentrations after resolution of HTGL warrants further study.

Peritoneal calprotectin level in peritoneal dialysis patients.

Calprotectin is an important molecule in the initiation and progression of the inflammatory process. Systemic and local intraperitoneal inflammation are distinct processes and consequences in peritoneal dialysis (PD). We aimed to evaluate dialysate calprotectin levels and its associations with peritonitis and dialysis adequacy in PD patients. Forty-four PD patients were included in this prospective study. Calprotectin concentration was evaluated in 24-h peritoneal drainage fluid. Patients were followed-up for 1 year, and peritonitis episodes were recorded. Dialysate calprotectin levels were compared to dialysis adequacy parameters and peritonitis frequency. The mean age of patients was 54.9±12.7 years. Median PD duration was 54 (23-76) months. Seventeen patients (38.6%) had previous peritonitis episodes. During follow-up, 15 of 44 patients (34.1%) had peritonitis. The median calprotectin concentration was 79.5 (75.2-86.3) ng/ml. The patients were divided into low and high calprotectin groups according to median value. In the high calprotectin group, BMI was found higher (p = 0.04). There was no significant relationship between calprotectin concentration and peritonitis during follow-up (p = 0.29). However, the patients that have had previous peritonitis had higher calprotectin concentrations (p = 0.02). The patients who had higher erythrocyte sedimentation rate (ESR) levels also had higher calprotectin concentrations (p = 0.01). Peritoneal calprotectin concentrations were correlated with higher BMI and ESR, and it was higher in patients with previous peritonitis episodes. To our knowledge, this is the first study to examine the peritoneal calprotectin levels in PD patients. Further studies are needed to determine the use of peritoneal calprotectin as an inflammatory marker in PD.

Effect of chronic and acute enterotoxigenic E. coli challenge on growth performance, intestinal inflammation, microbiome, and metabolome of weaned piglets

Post-weaning enteropathies in swine caused by pathogenic E. coli, such as post-weaning diarrhea (PWD) or edema disease (ED), remain a significant problem for the swine industry. Reduction in the use of antibiotics over concerns of antibiotic resistance and public health concerns, necessitate the evaluation of effective antibiotic alternatives to prevent significant loss of livestock and/or reductions in swine growth performance. For this purpose, an appropriate piglet model of pathogenic E. coli enteropathy is required. In this study, we attempted to induce clinical signs of post-weaning disease in a piglet model using a one-time acute or lower daily chronic dose of a pathogenic E. coli strain containing genes for both heat stable and labile toxins, as well as Shiga toxin. The induced disease state was monitored by determining fecal shedding and colonization of the challenge strain, animal growth performance, cytokine levels, fecal calprotectin, histology, fecal metabolomics, and fecal microbiome shifts. The most informative analyses were colonization and shedding of the pathogen, serum cytokines, metabolomics, and targeted metagenomics to determine dysbiosis. Histopathological changes of the gastrointestinal (GI) tract and tight junction leakage as measured by fecal calprotectin concentrations were not observed. Chronic dosing was similar to the acute regimen suggesting that a high dose of pathogen, as used in many studies, may not be necessary. The piglet disease model presented here can be used to evaluate alternative PWD treatment options.

Plasma Calprotectin Is Predictive for Short-Term Functional Outcomes of Acute Ischemic Stroke.

BackgroundBlood-based prognostic biomarkers of acute ischemic stroke (AIS) are limiting. Calprotectin is suggested to be involved in directing post-stroke inflammatory conditions. However, the pathological alteration of circulating calprotectin in AIS is yet to be thoroughly elucidated. Therefore, this study aimed to investigate the levels and clinical relevance of calprotectin in AIS.MethodsThis study recruited 271 patients with AIS within 24 h since symptom onset and 145 non-stroke healthy controls (HC) from February 1, 2018, to Dec 31, 2020. Patients were followed up for 2 weeks for observation of functional outcomes, as determined by the National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS). Plasma calprotectin concentrations were determined by ELISA.ResultsPlasma calprotectin concentrations were significantly higher in patients with AIS compared with controls [patients vs. control: median (IQR) 54.2 (39.01–99.04) vs. 50.04 (35.42–61.22), p < 0.001]. Besides, patients with poor prognosis, as defined by mRS ≥ 3, had significantly higher calprotectin levels than patients with good prognosis [poor prognosis patients vs. good prognosis patients: median (IQR) 61.99 (47.52–108) vs. 43.36 (33.39–60.2), p < 0.001]. Plasma calprotectin levels were positively associated with the disease severity of AIS, as reflected by infarction volume and NIHSS score at baseline. Furthermore, baseline calprotectin was found to be independently associated with poor prognosis [odds ratio (OR): 1.02, 95% CI: 1.01–1.03] and disease progression (OR: 1.03, 95% CI: 1.02–1.04) of AIS during a 2-week follow-up, with adjustment of possible confounding factors.ConclusionPlasma calprotectin is associated with short-term functional outcomes of AIS.

Evaluation of a faecal calprotectin method using the OC-SENSOR PLEDIA.

The National Institute for Health and Care Excellence recommends faecal calprotectin (f-cal) to help differentiate inflammatory bowel diseases from irritable bowel syndrome. Faecal samples for calprotectin have historically been collected at home by patients into screw-top pots and sent to laboratories where calprotectin is extracted and analysed. Faecal haemoglobin (f-Hb) samples are collected at home into specific collection devices containing stabilising buffer. We evaluated the OC-FCa method for f-cal, developed by Eiken Chemical Co., Ltd. (Japan) that uses the same collection device and analyser as f-Hb. OC-FCa was assessed for limit of blank (LOB), limit of detection (LOD), limit of quantification (LOQ), within and between-run imprecision, linearity, prozone, recovery and carryover. A method comparison against the BÜHLMANN fCAL® turbo (BÜHLMANN Laboratories AG, Switzerland) was performed using patient samples and EQA. The LOB was 3µg calprotectin/g faeces (µg/g), LOD 8μg/g and LOQ 20μg/g. Within and between-run imprecision was <5%; linearity was good (R2>0.99); prozone was appropriately detected; recovery was 99.6%; no observed carryover. OC-FCa showed a strong positive bias compared with BÜHLMANN fCAL® turbo (Z=-5.3587, p<0.001). When categorised using our local pathway, which interprets calprotectin concentrations and need forfurther investigation, Cohen's Kappa demonstrates substantial agreement at <50μg/g (κ=0.80) and >150μg/g (κ=0.63) and fair agreement (κ=0.22) in the borderline category 50-150μg/g. The OC-FCa method performed well in the evaluation. With the lack of standardisation for f-cal a clinical study is required to evaluate the positive bias and establish suitable cut-off levels.

Fecal Calprotectin in Children Can Differentiate Between Different Gastrointestinal Diseases

BACKGROUND: Calprotectin is a 36 kDa member of the S100 family of proteins. It is derived predominantly from neutrophils and has direct antimicrobial effects and a role within the innate immune response. Calprotectin is found in various body fluids in proportion to the degree of any existing inflammation and its concentration in feces is about 6 times that of plasma. Measurement of fecal calprotectin is a useful surrogate marker of gastrointestinal inflammation. It has a high negative predictive value in ruling out inflammatory bowel disease (IBD) in undiagnosed, symptomatic patients and high sensitivity for diagnosing the disease making it useful as a tool for prioritizing endoscopy. In patients with known IBD, fecal calprotectin can be a useful tool to assist management, providing evidence of relapse or mucosal healing to enable therapy to be intensified or reduced. AIM: The present study aimed to discuss the use of calprotectin for the diagnosis of IBD and some of the other ways in which the test may be useful in the management of gastroenterology patients. METHODS: A cross-sectional study on children with significant gastrointestinal diseases attending to pediatric department at Menoufia University, with a total number of 180 patients in addition to 30 normal children as control according to sample size calculation. The children are allocated into seven groups according to the final diagnosis to Group (1): 30 patients with IBD, Group (2): 20 patients with eosinophilic colitis, Group (3): 30 patients with Helicobacter pylori infection, Group (4): 40 patients with functional constipation, Group (5): 30 patients with cow milk allergy, Group (6): 30 patients with Celiac disease, and Group (7): 30 normal children as control. RESULTS: In cow milk protein allergic patients with marked GI presentation in the form of bloody diarrhea and/or abdominal distension, the mean fecal calprotectin (FC) was 1260 ± 625 μg/g. FC has decreased after 2−4 weeks of elimination of cow milk products to 420 ± 190 μg/g. Patient with inflammatory bowel disease had mean FC 4640 ± 850 μg/g, decreased after medical treatment and resolution of symptoms to 1360 ± 520 μg/g. In H. pylori infection detected by upper GI endoscopy and histopathology with positive stool antigen the mean FC was 78.9 ± 25.1 μg/g. Celiac disease patients had mean fecal calprotectin 456 ± 123 μg/g. Eosinophilic esophagitis had mean fecal calprotectin 4.2 ± 2.9 μg/g. Functional constipation patients had mean fecal calprotectin 23.6 ± 21.8 μg/g. Normal control children had mean fecal calprotectin 4.1 ± 6.9 μg/g. CONCLUSION: According to the results of previous studies, fecal calprotectin can be considered as a biomarker to differentiate between IBS and organic gastrointestinal disorders. However, due to the limitations of pre-analysis, a low fecal calprotectin concentration may not necessarily be considered as the reason for the absence of IBD.

Calprotectin levels in amniotic fluid in relation to intra-amniotic inflammation and infection in women with preterm labor with intact membranes: A retrospective cohort study

ObjectiveTo evaluate the concentrations of calprotectin in amniotic fluid with respect to intra-amniotic inflammation and infection and to assess the presence or absence of bacteria in the amnio-chorionic niche with respect to presence or absence of intra-amniotic inflammation. Study designSeventy-nine women with singleton pregnancies and preterm labor with intact membranes (PTL) were included in the study. Amniotic fluid was collected at the time of admission by amniocentesis and calprotectin levels were analyzed from frozen/thawed samples using ELISA. Interleukin (IL)-6 concentration was measured by point-of-care test. Samples from amniotic fluid and the amnio-chorionic niche (space between amniotic and chorionic membranes) were microbiologically analyzed. Microbial invasion of the amniotic cavity (MIAC) was diagnosed based on a positive PCR result for Ureaplasma species, Mycoplasma hominis, 16S rRNA or positive culture. Intra-amniotic inflammation (IAI) was defined as amniotic fluid point-of-care IL-6 concentration ≥ 745 pg/mL. The cohort of included women was divided into 4 subgroups based on the presence or absence of IAI/MIAC; i) intra-amniotic infection, ii) sterile IAI, iii) intra-amniotic colonization and iv) neither MIAC nor IAI. ResultsWomen with intra-amniotic infection had a significantly higher intra-amniotic calprotectin concentration (median; 101.6 µg/mL) compared with women with sterile IAI (median; 9.2 µg/mL), women with intra-amniotic colonization (median; 2.6 µg/mL) and women with neither MIAC nor IAI (median 4.6 µg/mL) (p = 0.001). Moreover, significantly higher amniotic fluid calprotectin concentration was seen in women who delivered within 7 days (p = 0.003). A significant negative correlation was found between amniotic fluid calprotectin and gestational age at delivery (rho = 0.32, p = 0.003). Relatively more bacteria in the amnio-chorionic niche were found in the sterile IAI group compared with the other groups. ConclusionsCalprotectin concentrations in amniotic fluid were significantly higher in the intra-amniotic infection group compared with the other groups. Moreover, the bacterial presence in the amnio-chorionic niche was higher in IAI group.

A switch from originator-adalimumab to the biosimilar SB5 in patients with Crohn’s disease: an analysis of two propensity score-matched cohorts

Background/aims Originator-adalimumab, an established treatment for patients with Crohn’s disease (CD), showed no difference in efficacy or adverse events versus adalimumab biosimilar SB5 (SB5-adalimumab) over 10 weeks (W) of treatment. To understand the long-term effectiveness of SB5-adalimumab in CD, patients switched from originator-adalimumab to SB5-adalimumab were compared with patients remaining on originator-adalimumab over 104 W. Methods Data on patients aged ≥18 years, diagnosed with CD and treated at ISCARE, were collected prospectively from July 2018 to January 2021. Primary outcome: clinical disease activity at W52, measured by Harvey-Bradshaw index (HBI). Secondary outcomes: C-reactive protein (CRP), faecal calprotectin (FC) and adalimumab concentrations at W10, 26, 52 and 104, and treatment persistence. To ensure comparable cohorts, patients were propensity score (PS)-matched for age, gender and disease activity. Results After matching, 54 patients remained per cohort. At W52, mean (SD) HBI score was 3.2 (2.5) for originator-adalimumab and 4.0 [3.6] for SB5-adalimumab (difference [95% CI] −0.78 [−2.8, 1.3]; n = 18/cohort); no clinically meaningful differences in CRP, FC or drug concentrations were noted. Kaplan–Meier’s estimates (95% CI) of remaining on treatment were originator-adalimumab: 0.870 (0.785–0.965) versus SB5-adalimumab: 0.648 (0.533–0.789) at W52 and significantly lower for SB5-adalimumab versus originator-adalimumab (p < .001) over 104 W. Local skin reaction events/pain was the main reason for treatment discontinuation in the SB5-adalimumab cohort (n = 20/54 [37%]). Conclusions These long-term results of CD patients receiving originator-adalimumab or following nonmedical switch to SB5-adalimumab show similar therapeutic effects on clinical disease activity, biological parameters and pharmacokinetic profile in both cohorts from 52 to 104 W. A separation in persistence was observed beyond W26, mainly due to differences in local reactions at the injection site.