Marker For Inflammatory Bowel Disease Research Articles

PMD65 - Faecal Calprotectin as A Diagnostic Marker of Inflammatory Bowel Disease in Patients with Gastrointestinal Symptoms - is It Cost-Effective Procedure in Primary Care in Poland?

PMD65 - Faecal Calprotectin as A Diagnostic Marker of Inflammatory Bowel Disease in Patients with Gastrointestinal Symptoms - is It Cost-Effective Procedure in Primary Care in Poland?

Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis

We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta-analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima-media thickness (CIMT), flow-mediated dilation (FMD%), and carotid-femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [ SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% ( SMD, -0.721%; 95% CI, -1.020 to -0.421; P < .0001), and significantly increased cfPWV ( SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

Subclinical Atherosclerosis in Patients With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.

We evaluated the differences in major markers of cardiovascular (CV) risk between inflammatory bowel diseases (IBDs) and controls by a systematic review and a meta-analysis. We searched PubMed, EMBASE, and Cochrane databases for literature comparing CV risk markers in IBDs and controls. The overall mean carotid intima-media thickness (CIMT), flow-mediated dilation (FMD%), and carotid-femoral pulse wave velocity (cfPWV) difference between patients with IBDs and control groups were calculated. Twenty-eight studies were included in the meta-analysis, including 16 studies with data on CIMT, 7 studies reporting FMD%, and 9 studies on cfPWV. Compared to controls, patients with IBDs showed significantly higher CIMT (standardized mean difference [ SMD]: 0.534 mm; 95% confidence interval [CI], 0.230 to 0.838; P = .001), significantly lower FMD% ( SMD, -0.721%; 95% CI, -1.020 to -0.421; P < .0001), and significantly increased cfPWV ( SMD, 0.849; 95% CI, 0.589 to 1.110; P < .0001). When analyzing subgroups with ulcerative colitis and Crohn disease (CD), all results were still significant except CIMT in CD. Our findings support the current evidence for an elevated CV burden in patients with IBD and support the clinical utility of markers of subclinical atherosclerosis in the management of these patients.

Active cytomegalovirus infection diagnosed by real-time PCR in patients with inflammatory bowel disease: a prospective, controlled observational study

Objective: It is assumed that cytomegaloviral (CMV) infection in inflammatory bowel disease (IBD) is caused by reactivation due to the immunosuppressive therapy, but the role of CMV as a pathophysiological factor and prognostic marker in IBD is unclear. The aim of this study was to investigate CMV infection in IBD, with real-time polymerase chain reaction (PCR) and immunohistochemistry, with emphasis on newly diagnosed disease.Materials and methods: In this prospective, controlled study, 67 patients with IBD and 34 control patients with irritable bowel syndrome (IBS) or rectal bleeding were included. Serology for CMV was analysed along with CMV DNA in plasma, mucosal biopsies, and faeces. Mucosal biopsies were further analysed with histopathology and CMV immunohistochemistry.Results: Detection of CMV IgM was more common in patients with IBD, compared to controls, 21% versus 3%. CMV DNA was found in 16% of patients with newly diagnosed, untreated IBD and in 38% of steroid-treated patients. Four of the five patients that needed urgent surgery were CMV-DNA positive in at least one of three sample types. None of the controls had detectable CMV DNA.Conclusions: Active CMV infection was found in high proportions of newly diagnosed untreated patients with IBD, in patients on immunosuppression and in patients in the need of surgery. Low CMV-DNA levels in non-immunosuppressed patients were not a risk factor for the development of more severe IBD, while the detection of CMV DNA in patients on immunosuppressive therapy may foresee disease progression.

B Cell-Activating Factor as a New Potential Marker in Inflammatory Bowel Disease.

B cell-activating factor (BAFF) has been proposed to be a regulator of B cell and T cell immune responses and be associated with inflammatory processes in autoimmunity and B cell malignancies. No study has reported the role of BAFF in inflammatory bowel disease (IBD). The purpose of this study was to investigate expression and concentrations of BAFF in IBD and determine its value to discriminate patients with IBD. Seventy-eight ulcerative colitis (UC) patients, 37 Crohn's disease (CD) patients, 12 irritable bowel syndrome (IBS) patients and 44 healthy controls were recruited. We examined serum and faecal BAFF levels using enzyme-linked immunosorbent assay. Intestinal BAFF expression was analysed in biopsies obtained from IBD patients. Intestinal mucosa localization of BAFF was conducted by immunofluorescence. The median (25th-75th percentile) serum BAFF concentration (pg/ml) was 1430 (1105-1624) in CD patients, 1472 (1018-1772) in UC patients and 977 (482-1345) in healthy controls. Serum BAFF was 64% sensitive and 93% specific for identifying active IBD from healthy controls. The BAFF expression was significantly increased in biopsy specimens from IBD patients. Fecal BAFF concentration was 369 (326-493) pg/ml in CD patients, 542 (358-1758) pg/ml in UC patients, 294 (287-299) pg/ml in IBS patients and 295 (284-309) pg/ml in healthy controls. Fecal BAFF was 90% sensitive and 96% specific for identifying active IBD from healthy controls and IBS patients. The novel association between BAFF and IBD seems to identify that BAFF might regulate the inflammatory process in these diseases and it appears to be a potential marker of IBD.

185 Novel Stool DNA Markers for Inflammatory Bowel Disease Associated Colorectal Cancer and High Grade Dysplasia: High Specificity Across Three Independent International Populations

185 Novel Stool DNA Markers for Inflammatory Bowel Disease Associated Colorectal Cancer and High Grade Dysplasia: High Specificity Across Three Independent International Populations

P726. TNFAIP6 is a disease activity marker in inflammatory bowel disease

P726. TNFAIP6 is a disease activity marker in inflammatory bowel disease

Application of fecal markers in inflammatory bowel disease

Application of fecal markers in inflammatory bowel disease

A galectin-specific signature in the gut delineates Crohn's disease and ulcerative colitis from other human inflammatory intestinal disorders.

Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gastrointestinal tract including Crohn's disease (CD) and ulcerative colitis (UC). Galectins, defined by shared consensus amino acid sequence and affinity for β-galactosides, are critical modulators of the inflammatory response. However, the relevance of the galectin network in the pathogenesis of human IBD has not yet been explored. Here, we analyzed the expression of relevant members of the galectin family in intestinal biopsies, and identified their contribution as novel mucosal markers in IBD. Colonic biopsies were obtained from 59 IBD patients (22 CD and 37 UC), 9 patients with gut rejection after transplantation, 8 adult celiac patients, and 32 non-IBD donors. Galectin mRNA expression was analyzed by RT-PCR and qPCR using specific primers for individual galectins. A linear discriminant analysis (LDA) was used to analyze galectin expression in individual intestinal samples. Expression of common mucosal-associated galectins (Gal-1, -3, -4, -9) is dysregulated in inflamed tissues of IBD patients compared with non-inflamed IBD or control samples. LDA discriminated between different inflammation grades in active IBD and showed that remission IBD samples were clusterized with control samples. Galectin profiling could not distinguish CD and UC. Furthermore, inflamed IBD was discriminated from inflamed tissue of rejected gut in transplanted patients and duodenum of celiac patients, which could not be distinguished from control duodenum samples. The integrative analysis of galectins discriminated IBD from other intestinal inflammatory conditions and could be used as potential mucosal biomarker.

Neutrophil anti-neutrophil cytoplasmic autoantibody proteins: bactericidal increasing protein, lactoferrin, cathepsin, and elastase as serological markers of inflammatory bowel and other diseases.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract comprising Crohn’s disease and ulcerative colitis. Although the pathogenesis of the disease is not clearly defined yet, environmental, genetic and other factors contribute to the onset of the disease. Apart from the clinical and histopathological findings, several serological biomarkers are also employed to detect IBD. One of the most thoroughly studied biomarker is anti-neutrophil cytoplasmic autoantibody (ANCA). We herein provide an overview of the current knowledge on the use of ANCA and certain ANCA proteins, such as bactericidal increasing protein, lactoferrin, cathepsin G and elastase, as serological markers for IBD and other diseases.

Fecal immunochemical test as a biomarker for inflammatory bowel diseases: can it rival fecal calprotectin?

Accurate evaluation of disease activity is essential for choosing an appropriate treatment and follow-up plan for patients with inflammatory bowel disease (IBD). Endoscopy is required for accurately evaluating disease activity, but the procedures are sometimes invasive and burdensome to patients. Therefore, alternative non-invasive methods for evaluating or predicting disease activity including mucosal status are desirable. Fecal calprotectin (Fcal) is the most widely used fecal marker for IBD, and many articles have described the performance of the marker in predicting disease activity, mucosal healing (MH), treatment efficacy, and risk of relapse. Fecal immunochemical test (FIT) can quantify the concentration of hemoglobin in stool and was originally used for the screening of colorectal cancer. We recently reported that FIT is also a useful biomarker for IBD. A direct comparison between the use of Fcal and FIT showed that both methods predicted MH in ulcerative colitis equally well. However, in the case of Crohn's disease, FIT was less sensitive to lesions in the small intestine, compared to Fcal. FIT holds several advantages over Fcal in regards to user-friendliness, including a lower cost, easy and clean handling, and the ability to make rapid measurements by using an automated measurement system. However, there is insufficient data to support the application of FIT in IBD. Further studies into the use of FIT for evaluating the inflammatory status of IBD are warranted.

Inflammatory bowel disease severity and activity are correlated to thyroid gland nodularity, chronic nonthyroidal illness, and thyroid autoantibodies but not thyroid dysfunction

Introduction An association between inflammatory bowel disease (IBD) and autoimmune thyroid disease (AITD) exists. The aim of the present study was to evaluate thyroid nodules, function, and antibodies in patients with IBD. Patients and materials The study included 50 patients with established diagnosis of IBD either ulcerative colitis (UC) or Crohn’s disease and 25 healthy controls. They were classified into two groups: group I included 25 patients with UC, and group II included 25 patients with Crohn’s disease; the control group included 25 healthy individuals. They were subjected to history taking, complete physical examination, and laboratory investigations that included evaluation of erythrocyte sedimentation rate (ESR), C-reactive protein, fecal calprotectin, free T3, free T4, thyroid-stimulating hormone, antithyroid peroxidase (TPO), antithyroglobulin (TG), and TSH receptor antibodies. Ileocolonoscopic and histopathological examination with assessment of IBD activity and thyroid ultrasonography were carried out. Results There were no statistically significant differences between the three groups as regards anti-TG antibodies (P=0.075), anti-TPO (P=0.190), AITD assessed serologically or by means of ultrasound (P=1.000), or as regards thyroid status (P=0.528). IBD patients had significantly more thyroid nodules compared with controls (P<0.001), and there was a positive correlation between IBD markers of activity (ESR and fecal calprotectin) and the presence of nodules. A significant negative correlation existed between free T3 and fecal calprotectin, ESR, and C-reactive protein, as well as between free T4 and ESR and fecal calprotectin. A significant positive correlation between anti-TG antibodies and fecal calprotectin as well as between anti-TPO antibodies and histological activity assessment of UC patients also existed. We found a significant negative correlation between free T3 and free T4 and several indices of IBD activity/severity. Conclusion AITD and altered thyroid function were the same among IBD patients and controls. However, IBD patients had significantly more nodules; indices of activity/severity of IBD correlated negatively with free T3 and T4, and positively with anti-TPO, anti-TG, and nodularity.

Bacteria-Derived Compatible Solutes Ectoine and 5α-Hydroxyectoine Act as Intestinal Barrier Stabilizers to Ameliorate Experimental Inflammatory Bowel Disease.

Earlier studies showed that the compatible solute ectoine (1) given prophylactically before induction of colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats prevented histological changes induced in the colon and the associated rise in inflammatory mediators. This study was therefore conducted to investigate whether ectoine (1) and its 5α-hydroxy derivative (2) would also be effective in treating an already established condition. Two days after inducing colitis in rats by instilling TNBS/alcohol in the colon, animals were treated orally once daily for 1 week with either 1 or 2 (50, 100, 300 mg/kg). Twenty-four hours after the last drug administration rats were sacrificed. Ulcerative lesions and colon mass indices were reduced by 1 and 2 in a bell-shaped manner. Best results were obtained with 100 mg/kg ectoine (1) and 50 mg/kg 5α-hydroxyectoine (2). The solutes normalized the rise in myeloperoxidase, TNFα, and IL-1β induced by TNBS but did not affect levels of reduced glutathione or ICAM-1, while reducing the level of fecal calprotectin, an established marker for inflammatory bowel disease. The findings indicate that the naturally occurring compatible solutes ectoine (1) and 5α-hydroxyectoine (2) possess an optimum concentration that affords maximal intestinal barrier stabilization and could therefore prove useful for better management of human inflammatory bowel disease.

Fecal Calprotectin as an Activity Marker of Inflammatory Bowel Disease in Children.

Children constitute 20% of patients with inflammatory bowel diseases (IBD). Still there is asearch for aperfect marker for this group of patients which would help in the diagnosis of the disease, in determinating its activity and in monitoring the treatment. Evaluate the usefulness of the application of calprotectin measurement in stool samples from children with IBD, as amarker of the severity of inflammation. We analysed 156patients: 58 with ulcerative colitis (UC), 67 with Crohn's disease (CD), and 31 from the control group. In all patients the concentration of calprotectin in the sample of feces, markers of inflammation and hemoglobin were measured. Concentration of calprotectin in feces of patients with IBD was above the normal range in all patients with moderate and severe disease and in the majority with mild disease or in remission, but it was normal in all patients from the control group. Elevated concentration of fecal calprotectin (FC) was observed in the majority of patients with IBD, but in none from the control group. The number of patients with elevated FC concentration increased together with the disease activity. FC concentration was higher in patients with severe and moderate disease activity. FC concentration in patients with IBD was associated with the increase of inflammatory markers and decreased haemoglobin. Percentage of laboratory abnormalities in children with Crohn's disease and perianal changes was higher. FC concentration can be anoninvasive marker of disease activity in IBD.

High Incidence of Serologic Markers of Inflammatory Bowel Disease in Asymptomatic Patients with Glycogen Storage Disease Type Ia.

Most patients with glycogen storage disease (GSD) type Ib show features related to inflammatory bowel disease (IBD). The development of IBD seems to be associated with the defect of neutrophil function in GSD Ib. Patients with GSD Ia were not recognized to have similar gastrointestinal complaints until recently and are not associated with a neutrophil defect. Fifty consecutive GSD Ia inpatients over the age of 2 years without a diagnosis of IBD were screened using serologic and genetic markers via the Prometheus IBD sgi Diagnostic test. Eleven patients were tested positive for IBD (22%), with five fitting the pattern for Crohn's disease, five for ulcerative colitis, and one with nonspecific IBD. Only 2 out of the 11 patients had any gastrointestinal complaints. No pattern could be distinguished from individual inflammatory markers, genetics, inflammation antibodies, age, complications, or metabolic control. Of note, 9 out of 11 patients testing positive were female. Patients with GSD Ia were found to have a higher rate of serologically indicated IBD when compared with the general population. While these subjects will need to be followed to determine if these serologic markers correlate with clinical disease, this study supports that IBD may be more common in the GSD Ia population. Further studies are warranted to explain the relationship between IBD and GSD I since it may provide clues regarding the pathogenesis of IBD development in the general population.

An Evaluation of the Correlation between Hepcidin Serum Levels and Disease Activity in Inflammatory Bowel Disease.

Aim. While there are many well-defined serological markers for inflammatory bowel disease (IBD), there is limited evidence that they positively affect clinical outcomes. This study aimed to evaluate the correlation between hepcidin serum levels and disease activity in IBD. Materials and Methods. Eighty-five consecutive IBD patients were enrolled in the study. Hepcidin serum levels were assessed using an enzyme-linked immunosorbent assay (ELISA) and were compared with disease activity as well as the interleukin-6 (IL-6) and C-reactive protein (CRP) levels. Results. The mean hepcidin serum levels in Crohn's disease (CD) patients in remission and in the active phase were 3837 ± 1436 and 3752 ± 1274 pg/mL, respectively (P = 0.613). The mean hepcidin serum levels in ulcerative colitis (UC) patients in remission and in the active phase were 4285 ± 8623 and 3727 ± 1176 pg/mL, respectively (P = 0.241). Correlation analysis between inflammatory markers and hepcidin serum levels indicated that there was no correlation between hepcidin levels and IL-6 (P = 0.582) or CRP (P = 0.783). Conclusion. As an acute-phase protein, hepcidin seems to have a lower efficacy than other parameters in the detection of activation in IBD.

The role and utility of faecal markers in inflammatory bowel disease.

Crohn's disease and ulcerative colitis are characterized by periods of symptomatic relapse and remission. Diagnosis and assessment of inflammatory bowel disease has so far been based on clinical evaluation, serum parameters, radiology and endoscopy. Faecal markers such as calprotectin or lactoferrin have emerged as new diagnostic tools to detect and monitor intestinal inflammation. This review focuses on their potential clinical applications and limitations in the management of inflammatory bowel disease.

P-049: Reproducibility of serologic antibody activity at diagnosis and after treatment in pediatric ulcerative colitis and Crohn’s disease

P-049: Reproducibility of serologic antibody activity at diagnosis and after treatment in pediatric ulcerative colitis and Crohn’s disease

Elevation of PRKCDBP, a novel transcriptional target of TNF-α, and its downregulation by infliximab in patients with ulcerative colitis.

Protein kinase C delta binding protein (PRKCDBP/Cavin3/hSRBC) is a putative tumor suppressor that is downregulated in many human cancers. Recently, PRKCDBP was identified to be activated by nuclear factor-κB in response to tumor necrosis factor (TNF)-α. To explore the potential of PRKCDBP as a diagnostic or prognostic marker for inflammatory bowel disease, the possible correlation between its expression status and TNF-α signaling was evaluated in ulcerative colitis (UC) patients, both pre- and post-infliximab (IFX) therapy. In total, 31 IFX therapy-naïve patients (13 females; median age, 41 years) with moderate-to-severe UC who had been scheduled for IFX treatment were included. Immunohistochemical analysis of TNF-α and PRKCDBP expression was performed in rectal biopsies. A significant correlation was observed in immunoreactivity between TNF-α and PRKCDBP. IFX therapy reduced immunohistochemical expression of PRKCDBP and TNF-α (P < 0.001 and P = 0.005, respectively). The mean PRKCDBP expression level decreased from 54.5 to 30.2%, and that of TNF-α decreased from 54.5 to 36.2%. The immunohistochemical expression pre- and post-PRKCDBP therapy correlated significantly with TNF-α levels pre- and post-therapy (Spearman's rank correlation test; P = 0.005 and P = 0.001, respectively). These results demonstrate that mucosal expression of PRKCDBP correlated strongly with TNF-α expression in UC patients and that IFX therapy resulted in profound reductions in both PRKCDBP and TNF-α. Thus, these findings support that PRKCDBP expression is tightly controlled by TNF-α, and the anti-inflammatory effect of IFX may in part stem from blockade of the TNF-α-PRKCDBP signaling pathway.

Prevalence of Hepatitis-B Viral Markers in Patients With Inflammatory Bowel Disease in a Hepatitis-B-Endemic Area

There are few data regarding the prevalence of hepatitis-B virus (HBV) markers in inflammatory bowel disease (IBD) patients in Korea, which is a hepatitis-B-endemic area. The aim of this study was to assess the prevalence of HBV markers in IBD patients in comparison with controls. We enrolled 513 IBD patients [241 Crohn's disease (CD) and 272 ulcerative colitis (UC)] whose hepatitis-B surface antigen and anti-HBs levels were evaluated. Anti-HBc was assayed in 357 patients. These markers were compared with those of 1020 sex-matched and age-matched controls. Prevalence of hepatitis-B surface antigen in IBD patients was 3.7% and there was no significant difference between groups (CD 4.1%, UC 3.3%, control 4.4%, P=0.713). The frequency of effective vaccination against HBV (positive anti-HBs, without anti-HBc) was lower in IBD patients less than 30 years old compared with the same-aged controls (CD 43.3%, UC 48.5%, control 61.9%, P=0.002), whereas there was no difference between groups in subjects more than 30 years old. One third of IBD patients were at risk of susceptibility to HBV infection (nonimmune), particularly those less than 30 years old, compared with controls of the same age (CD 43.3%, UC 36.4%, control 21%, P<0.001). In IBD patients, multivariate analysis identified that age less than 30 years was an independent risk factor for nonimmune status. IBD was not a risk factor for HBV infection even in endemic areas. However, many young IBD patients were susceptible to HBV infection. It is crucial to screen for HBV immunity and to implement a meticulous vaccination strategy for young Korean IBD patients.