Marker For Inflammatory Bowel Disease Research Articles

Evaluation of Serum Calprotectin Levels in Patients with Inflammatory Bowel Disease.

Fecal calprotectin has been proposed as a useful biomarker of disease activity in inflammatory bowel disease (IBD). However, the role of calprotectin in systemic circulation is not well established. Thus, this study aimed to quantify serum calprotectin levels to identify a potential inflammatory marker for IBD. Ninety-eight patients with ulcerative colitis (UC) and 105 patients with Crohn's disease (CD) were prospectively enrolled and clinically scored. Ninety-two healthy, age-matched subjects served as controls. Blood samples from UC and CD patients and controls were analyzed for serum calprotectin levels and routine laboratory parameters. Disease activity was assessed by partial Mayo score and Harvey-Bradshaw index for UC and CD, respectively. Serum calprotectin levels were higher in CD and UC patients than in controls and were higher during active disease than during inactive disease in CD but not in UC. In UC, serum calprotectin levels were correlated with C-reactive protein (CRP) but not with other laboratory parameters or disease activity. In CD, serum calprotectin levels were positively correlated with disease activity, serum CRP, and platelet count. In UC and CD, serum calprotectin and CRP levels increased during the acute phase and decreased towards remission. Serum calprotectin is an inflammatory marker in IBD but might be more effective in evaluating patients with CD than those with UC. Further studies are needed to confirm these findings and to better determine the specific uses of serum calprotectin in routine practice.

Cytomegalovirus Infection Exacerbates Experimental Colitis by Promoting IL-23 Production.

Many studies have demonstrated an association between cytomegalovirus (CMV) infection and inflammatory bowel disease (IBD). Moreover, CMV infection is more common in patients with severe or steroid-refractory IBD. However, it is not clarified whether CMV worsens IBD or if it is merely a surrogate marker for IBD. Here, we used the dextran sodium sulfate (DSS)-induced colitis model to investigate if CMV infection exacerbates colitis. The mice were injected intraperitoneally with 10 MOI of murine CMV (MCMV) and thereafter, chronic colitis was induced by one cycle of DSS exposure. Anti-IL-23R mAb at 20 μg/mice and pyrrolidine dithiocarbamate (PDTC), an effective NF-κB inhibitor, at 50 mg/kg were administrated to the mice. The MCMV-infected mice had a shorter colon length and a higher histopathology score than the mock inoculum-treated mice, while anti-IL-23R mAb administration ameliorated the pathological changes. Expression of IL-23, phospho-NF-κB p65, and phospho-IκBα was upregulated in colon tissues of the MCMV-infected mice compared to mock inoculum-treated mice, while treatment with PDTC attenuated colonic IL-23 production. These data demonstrated that CMV infection could accelerate IBD development. This effect may be due to its activation on NF-κB signaling pathway and subsequently IL-23 production.

Faecal calprotectin as a diagnostic marker of inflammatory bowel disease in patients with gastrointestinal symptoms: meta-analysis.

Colonoscopy is the standard medical procedure to identify inflammatory bowel disease (IBD) in patients with gastrointestinal symptoms. Noninvasive measurement of faecal calprotectin concentration may replace colonoscopy in this indication. The study aimed to assess efficacy of faecal calprotectin as a diagnostic marker of IBD in patients with symptoms suggestive of such diagnosis. Meta-analysis of diagnostic accuracy studies was performed. Cochrane, EMBASE and MEDLINE databases were searched until December 2018. Inclusion criteria comprised experimental and observational studies, adults with gastrointestinal symptoms, calprotectin as index and colonoscopy as reference test, presence of data on/enabling the calculation of diagnostic accuracy parameters. For each study, sensitivity and specificity of faecal calprotectin were analysed as bivariate data. Nineteen studies were identified. The total number of patients was 5032. Calculated pooled sensitivity and specificity were 0.882 [95% confidence interval (CI), 0.827-0.921] and 0.799 (95% CI, 0.693-0.875), respectively. Following faecal calprotectin incorporation in the diagnostic work-up of 100 people with suspected IBD, 18 non-IBD patients will have a colonoscopy performed and one patient with the disease will not be referred for this examination. Faecal calprotectin concentration measurement is a useful screening test to rule out IBD, at the same time reducing the need for colonoscopy by 66.7%.

IRF5 Acts As a Potential Therapeutic Marker in Inflammatory Bowel Disease

Background: Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronically inflammatory disorders. Interferon regulatory factor (IRF) 5 is reported to be involved in the pathogenesis of several inflammatory diseases. However, the exact role of IRF5 in IBD is still obscure. Materials and Methods: IRF5 expression was analyzed in peripheral blood mononuclear cells (PBMCs) and inflamed mucosa of patients with IBD by means of qRT-PCR and immunohistochemistry. Peripheral blood CD4+ T cells were stimulated with inflammatory cytokines, and transfected with lentivirus-expressing IRF5 (LV-IRF5) or LV-sh-IRF5, and then cytokine expression was determined by using Flow cytometry, qRT-PCR and ELISA. Results: IRF5 was significantly increased in PBMCs and inflamed mucosa in patients with active IBD, and was significantly correlated with disease activity. Upregulation of IRF5 not only could promote IBD CD4+ T cells to differentiate into Th1 and Th17 cells through modulation of T-bet and RORC, but also suppressed IL-10 expression via targeting its promoter sites directly, whereas downregulation of IRF5 had the opposite effects. TNF-α upregulated IRF5 expression in CD4+ T cells, and anti-TNF treatment with infliximab (IFX) could significantly decrease IRF5 expression in CD4+ T cells and intestinal mucosa in patients with CD. Conclusions: Our study reveal a novel mechanism in which elevated IRF5 levels in IBD were correlated with disease activity, and might serve as a potential therapeutic marker for the treatment of IBD via promoting Th1/17 cell immune responses and inhibiting IL-10 expression. Funding Statement: This work was supported by grants from the National Natural Science Foundation of China (81800501), the Natural Science Foundation of Shandong Province, China (ZR2018BH004), the key Research and Development Plan of Shandong Province (2018GSF118214), and the PhD Research Startup Foundation of the Affiliated Hospital of Jining Medical University (2017-BS-004). Declaration of Interests: The authors do not have any conflicts of interest. Ethics Approval Statement: This study was approved by the Institutional Review Board for Clinical Research of the Affiliated Hospital of Jining Medical University and the Shanghai Tenth People’s Hospital of Tongji University. Written informed consent was also obtained from all subjects before study.

Inflammatory bowel disease is associated with increased gut-to-blood penetration of short-chain fatty acids: A new, non-invasive marker of a functional intestinal lesion.

What is the central question of this study? 'Leaky gut' has been found in intestinal and extra-intestinal diseases. However, functional evaluation of intestinal permeability is not widely used as a diagnostic marker, possibly owing to significant limitations of currently used permeability assays. There is an unmet need for development of a new, non-invasive test to assess intestinal function. What is the main finding and its importance? We show that an increased blood-to-stool ratio of the concentration of gut bacteria-produced short-chain fatty acids may be used as a marker of gut permeability. Our findings lay the groundwork for establishing a new, non-invasive, risk-free diagnostic tool in diseases associated with intestinal barrier malfunction, such as inflammatory bowel disease. Intestinal diseases, such as inflammatory bowel disease (IBD), are characterized by an impaired gut-blood barrier commonly referred to as 'leaky gut'. Therefore, functional evaluation of the gut-blood barrier is a promising diagnostic marker. We hypothesized that short-chain fatty acids (SCFAs) produced by gut bacteria might serve as a marker in IBD. Animal experiments were performed on male Sprague-Dawley rats with acetic acid-induced colitis and in sham control animals. The gut-blood barrier permeability was determined by assessing the ratios of the following: (i) portal blood concentration of SCFAs (Cp ) to faecal concentration of SCFAs (Cf ); (ii) systemic blood concentration of SCFAs (Cs ) to faecal concentration of SCFAs (Cf ); and (iii) Cp and Cs of fluorescein isothiocyanate (FITC)-dextran administered into the colon. As a clinical study, we evaluated Cs , Cf and the Cs /Cf ratio of SCFAs in six paediatric patients with IBD, assessed as mild/moderate/severe by the Paediatric Ulcerative Colitis Activity Index (PUCAI) and the Paediatric Crohn's Disease Activity Index (PCDAI) at the time of sample collection, and nine age-matched healthy control subjects. Rats with histologically confirmed IBD had significantly increased ratios of Cp /Cf and Cs /Cf for SCFAs. This was positively correlated with the plasma FITC-dextran concentration. Likewise, IBD patients showed a significantly higher Cs /Cf ratio for SCFAs, including acetic, valeric, isocaproic, caproic and propionic acids, in comparison to control subjects. In conclusion, in the rats and in paediatric patients with IBD we found an increased blood-to-stool ratio of SCFAs, suggesting an increased gut-to-blood penetration of SCFAs. These findings pave the way for a new, non-invasive diagnostic tool in IBD and other diseases accompanied by intestinal barrier malfunction.

Reference Intervals for Fecal Calprotectin in Pregnant Women Using a Particle Enhanced Turbidimetric Assay.

Fecal calprotectin is widely used as a marker for inflammatory bowel diseases (IBD). IBD often affects women during their reproductive years, but there are no established reference intervals during pregnancy. The aim of the present study was to define reference values during pregnancy and in the postpartum period to allow comparisons between patient results and reference values. Fecal samples were collected from 84 healthy females during pregnancy week 26 to 28 and a second sample was collected six months after delivery. The samples were weighed, extracted, and centrifugated to remove debris. The extracted samples were then analyzed on a chemistry analyzer using a particle enhanced turbidimetric immunoassay reagent. The calculated reference interval during pregnancy was < 127 μg/g (90% confidence interval, 90 - 164 μg/g) and the corresponding reference interval during the postpartum period was < 143 μg/g (60 - 226 μg/g). There were no significant statistical differences between F-calprotectin values analyzed at the two sampling times. The reference values are slightly higher than the cutoff values of 50 - 100 μg/g often used as General cutoff for fecal calprotectin.

Peripheral Lymphocytes of Patients with Inflammatory Bowel Disease Have Altered Concentrations of Key Apoptosis Players: Preliminary Results.

Notwithstanding uncertain pathogenesis of inflammatory bowel disease (IBD), deregulation of adaptive immunity is paramount for the development of inflammation. Essential role in the resolution of inflammation is played by apoptosis, deregulated in lymphocytes isolated from inflamed intestine. Despite IBD being a systemic disease, little is known about apoptosis of peripheral lymphocytes. The concentrations of Bcl-2, cytochrome c, p53, and caspase-9 were determined (ELISA) in lymphocyte-enriched fractions of peripheral blood mononuclear cells (LE-PBMCs) from 64 individuals (42 with IBD) and related to IBD phenotype and activity, treatment, and inflammatory and hematological indices. The diagnostic potential of evaluated markers was determined as well. All evaluated molecules were significantly lower in IBD patients, of which cytochrome c and p53 were significantly lower exclusively in patients with Crohn's disease (CD) and cytochrome c differed significantly between CD and ulcerative colitis (UC). Caspase 9 was significantly lower in active IBD and Bcl-2 in active UC whereas cytochrome c was higher in active CD. Treatment with corticosteroids affected the concentrations of cytochrome c and p53. Both positively correlated with hsCRP and the concentrations of all markers were interrelated. As IBD markers, Bcl-2 and caspase-9 displayed good accuracy and, as a panel of markers with cytochrome c, their accuracy was excellent (92%). As CD markers Bcl-2, cytochrome c, and p53 displayed fair accuracy but combined determination of Bcl-2 and cytochrome c improved the accuracy to 85%. Taken together, our results imply diminished intrinsic apoptotic capacity of LE-PBMCs in IBD but an upregulation of proapoptotic features parallel to increasing severity of inflammation. Observed abnormalities in intrinsic pathway of apoptosis are more pronounced in CD. Upon positive validation on a larger set of patients, combined quantification of Bcl-2 and cytochrome c might be considered as an adjunct in differential diagnosis of UC and CD of colon and rectum.

Serum markers of Inflammatory Bowel Disease: A literature review

Background: The diagnosis, prognosis, assessment of disease activity and severity, as well as the outcome of therapy of inflammatory bowel disease (IBD), Crohn’s disease (CD), and ulcerative colitis (UC), remain a challenge for physicians treating this disorder. For each of these aspects, there is no single gold standard test or examination. Endoscopy accompanied by histology examination can confirm the diagnosis of IBD. Laboratory markers have been investigated in IBD for diagnostic and differential diagnostic purposes, assessment of disease activity and risk of complications, prediction of relapse, and for monitoring the effect of therapy. Objective: This article provides a review of the literature regarding IBD with the recommendation of prominent markers that can be used for diagnosing and monitoring the disease. Conclusion: C-reactive protein is an acute phase reactant which is best used to assess inflammation in IBD. Fecal calprotectin and lactoferrin are reliable fecal markers to monitor disease activity. The combination of serological marker P-ANCA and ASCA can be used to diagnose CD. In clinical practice, Crohn's Disease Activity Index (CDAI) is used as the primary tool for evaluating IBD.Â

Extraction, isolation, and concentration of calprotectin antigen (S100A8/S100A9) from granulocytes.

BackgroundCalprotectin is a promising biomarker for granulocyte activation. It is mainly measured in faeces as a marker for inflammatory bowel disease. A limitation is that there is no widely accepted calibrator.AimTo establish a method for purification of calprotectin from human granulocytes that is easily reproducible, reliable, and could contribute to a better agreement between different calprotectin methods.Methods and resultsCalprotectin was purified from granulocyte extracts using ion‐exchange chromatography. The granulocytes were separated from blood bags. The purity was analysed by analysing pixel density of a picture of the sodium dodecyl sulfate polyacrylamide gel electrophoresis and by size exclusion chromatography. The calprotectin concentration of the pure antigen solution was determined using Biuret method. The purity was >95% for 3 preparations, and their concentrations were 1079, 1080, and 1813 mg/L.ConclusionIt is possible to reproducibly prepare highly purified calprotectin antigen from human granulocytes. The preparations can be used for preparing calibrators, controls for immunological calprotectin assays, and immunisation for raising antibodies against human calprotectin in hens.

Diagnostic and clinical role of serum proteinase 3 antineutrophil cytoplasmic antibodies in inflammatory bowel disease.

Proteinase 3 antineutrophil cytoplasmic antibodies (PR3-ANCAs) are well-known serological markers for granulomatosis with polyangiitis, but their role as serological markers for inflammatory bowel disease remains uncertain. The present study aimed to evaluate the diagnostic and clinical role of PR3-ANCAs as markers for inflammatory bowel disease. Using a new methodology with chemiluminescence enzyme immunoassay, serum PR3-ANCA titers were assessed in 102 patients with ulcerative colitis (UC), 67 patients with Crohn's disease (CD), 44 controls with other intestinal diseases, and 66 healthy controls. Associations with clinical data were investigated. The diagnostic role of PR3-ANCAs was evaluated by receiver operating characteristic analysis. Proteinase 3 antineutrophil cytoplasmic antibody titers were significantly higher in patients with UC than in those with CD patients, patients with intestinal diseases (intestinal controls), and healthy controls (all P<0.001). Receiver operating characteristic analysis demonstrated an area under the curve of 0.85 (95% confidence interval: 0.83-0.87) and showed that the manufacturer's cutoff value (3.5U/mL) had a sensitivity of 39.2% and specificity of 96.6% for UC. There was a significant difference between PR3-ANCA-positive and PR3-ANCA-negative patients with regard to disease duration (P<0.05) and disease severity (P<0.01). Proteinase 3 antineutrophil cytoplasmic antibodies were significantly more prevalent in patients with UC than in those with CD and controls. Our results suggested the role of PR3-ANCAs as serological markers for aiding in diagnosing UC and evaluating disease severity. Further prospective studies are needed across multiple populations of patients and ethnic groups.

Intestinal inflammation markers in inflammatory bowel disease

During the past few decades, extensive researches were conducted to identify serological markers in patients with inflammatory bowel disease (IBD) that can reliably diagnose and monitor disease activity and help in predicting relapses. To date, several serological markers have been identified. This review will address the different serological markers and their clinical significance and applicability in medical practice. Serological markers include antibodies against microbial antigens, peptide antigens, autoantibodies, and basic inflammatory markers. Some serological markers such as anti-Saccharomyces cerevisiae antibodies (ASCA) and antibodies against exocrine pancreas (PAB) help the confirmation of the diagnosis of IBD to differentiate it from other non-IBD. Perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) and ASCA can distinguish Chron’s disease and ulcerative colitis. Certain markers can aid stratification of Chron’s disease including antibodies to Pseudomonas fluorescens associated sequence I2 (Anti-I2), antibodies to bacterial flagellin (Anti-CBir1), ASCA, and antibodies to outer membrane porin C (Anti-OmpC). ASCA and pANCA can predict disease response to therapeutic agents (e.g. Infliximab). ASCA can also unaffected family members at risk of developing Chron’s disease.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study.

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity.

Accuracy of fecal calprotectin for the prediction of endoscopic activity in patients with inflammatory bowel disease

BackgroundFecal calprotectin is a noninvasive marker of inflammatory bowel disease. AimTo evaluate the accuracy of calprotectin for prediction of endoscopic activity in inflammatory bowel disease. MethodsOne-hundred patients were prospectively included. Quantum Blue® (Bühlmann) kits were used to determine calprotectin. Endoscopic activity was calculated. Various serum markers (platelets, leukocytes, C-reactive protein, and albumin) were recorded. ResultsCalprotectin was higher in patients with endoscopic activity than in those without activity: in ulcerative colitis, with the low- (29 ± 14 vs. 301 ± 174, p < 0.001) and high- (99 ± 727 vs. 617 ± 801, p < 0.001); and in Crohn’s disease, with the low- (29 ± 59 vs. 124 ± 268, p < 0.01) and high-range kit (99 ± 37 vs. 287 ± 607, p < 0.01). Serological marker concentrations did not vary with endoscopic activity. The area under the ROC curve of calprotectin for the prediction of endoscopic activity was 0.9 in ulcerative colitis and 0.8 in Crohn’s disease. The best cut-off points for the detection of activity in ulcerative colitis were 50 for the low- (sensitivity 85%, specificity 79%) and 102 for the high- (sensitivity 85%, specificity 79%); in Crohn’s disease, 54 for the low- (sensitivity 71%, specificity 75%) and 122 for the high-range kit (sensitivity 71%, specificity 75%). ConclusionsFecal calprotectin concentration has good diagnostic accuracy for the detection of endoscopic activity in inflammatory bowel disease and performs better in ulcerative colitis than in Crohn’s disease.

Normal values for calprotectin in stool samples of infants from the population-based longitudinal born into life study

Faecal calprotectin is a protein used as a diagnostic marker for inflammatory bowel diseases. We determined upper limits for normal calprotectin values for neonatal, 6, 12 and 24 months old children using a turbidimetric immunoassay in a cohort of Swedish children. The advantage of the method is that opposite to previously used enzyme-linked immunosorbent assay (ELISA) method, it enables measuring single samples, and thus, shortens the analysis time significantly. There were 72 samples (41.7% female) collected neonatally, 63 samples (34.9% female) at 6 months, 60 samples (40.0% female) at 12 months and 51 samples (43.1% female) at 24 months. The upper limits for normal values were 233, 615, 136 and 57 µg mg−1 for infants aged 0, 6, 12 and 24 months, respectively.

Stability in metabolic phenotypes and inferred metagenome profiles before the onset of colitis-induced inflammation

Inflammatory bowel disease (IBD) is associated with altered microbiota composition and metabolism, but it is unclear whether these changes precede inflammation or are the result of it since current studies have mainly focused on changes after the onset of disease. We previously showed differences in mucus gut microbiota composition preceded colitis-induced inflammation and stool microbial differences only became apparent at colitis onset. In the present study, we aimed to investigate whether microbial dysbiosis was associated with differences in both predicted microbial gene content and endogenous metabolite profiles. We examined the functional potential of mucus and stool microbial communities in the mdr1a−/− mouse model of colitis and littermate controls using PICRUSt on 16S rRNA sequencing data. Our findings indicate that despite changes in microbial composition, microbial functional pathways were stable before and during the development of mucosal inflammation. LC-MS-based metabolic phenotyping (metabotyping) in urine samples confirmed that metabolite profiles in mdr1a−/− mice were remarkably unaffected by development of intestinal inflammation and there were no differences in previously published metabolic markers of IBD. Metabolic profiles did, however, discriminate the colitis-prone mdr1a−/− genotype from controls. Our results indicate resilience of the metabolic network irrespective of inflammation. Importantly as metabolites differentiated genotype, genotype-differentiating metabolites could potentially predict IBD risk.

Abstract 2700: Intestinal Vitamin D receptor deficiency increases susceptibility for the DSS-induced colon disease

Abstract To investigate the function of the intestinal Vdr gene in inflammatory bowel disease (IBD), in conjunction with the discovery of possible metabolic markers for IBD using intestine-specific Vdr knockout mice. VdrΔIEpC mice were generated, phenotyped and treated with a time-course of 3% dextran sulfate sodium (DSS) to induce colitis. Colitis was diagnosed by evaluating clinical symptoms and intestinal histopathology. Gene expression analysis was carried out. In addition, metabolic markers of IBD were explored by metabolomics. VdrΔIEpC mice showed abnormal body size, colon structures and feces color. Calcium, collagen, and intestinal proliferation-related gene expression were all decreased, and serum alkaline phosphatase was highly increased. In the acute model which was treated with 3% DSS for six days, VdrΔIEpC mice showed a high score of IBD symptoms; enlarged mucosal layer and damaged muscularis layer. In the recovery experiment model, where mice were treated with 3% DSS for four days and water for three days, VdrΔIEpC mice showed a high score of IBD symptoms; severe damage of mucosal layer and increased expression of genes encoding proinflammatory cytokines. Feces metabolomics revealed decreased concentrations of taurine, taurocholic acid, taurodeoxycholic acid and cholic acid in Vdr ΔIEpC mice. In conclusion, disruption of the intestinal Vdr gene showed phenotypical changes. These factors combined may exacerbate IBD. Taken together, the results suggest that VDR may play an important role in IBD. Citation Format: Jung-Hwan Kim, Satoshi Yamaori, Frank J. Gonzalez. Intestinal Vitamin D receptor deficiency increases susceptibility for the DSS-induced colon disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2700. doi:10.1158/1538-7445.AM2017-2700

Serum miRNA signature diagnoses and discriminates murine colitis subtypes and predicts ulcerative colitis in humans

Inflammatory bowel disease (IBD) is difficult to diagnose due to nonspecific and variable symptoms, and lack of reliable diagnostic tests. Current methods are invasive, non-sensitive, non-predictive, and do not easily discriminate between its two main forms. Consequently, there remains a great need for reliable serum markers for IBD. Here, using a longitudinal study of various mouse models of colitis, we identified a serum miRNA signature that indicated the development of colitis and discriminated between inflammations of various origins (colitis from arthritis). Unlike the existing biomarkers, the newly identified signature also serves to distinguish individuals at risk, predict the type of inflammation, and evaluate the response to therapeutics. Moreover, the miRNA signature identified in mice predicted ulcerative colitis with 83.3% accuracy. In future, the signature identified herein could play a central role in monitoring inflammatory disorders and therapeutic responses in patients, thereby paving the way for personalized medicine.

Serum Cyclophilin A Correlates with Increased Tissue MMP-9 in Patients with Ulcerative Colitis, but Not with Crohn's Disease.

Cyclophilin A (CyPA) is an immunomodulatory protein, high expression of which correlates with poor outcome of patients with inflammatory diseases. However, its role in inflammatory bowel disease (IBD) has not been studied. This study analyzes the correlation between cyclophilin A, matrix metalloproteinase (MMP)-9, and tissue inhibitor of MMP (TIMP)/MMP-9 complexes in the inflamed and non-inflamed colon mucosa of UC and CD patients. Serum and biopsy specimens from inflamed and non-inflamed colonic mucosa of 38 patients with IBD (19 with UC and 19 with CD) and 16 controls were included in our study. We measured serum and tissue level of CyPA, and tissue level of TNF-α, MMP-9, TIMP-1/MMP-9, and TIMP-2/MMP-9 using ELISA method. Our results indicated that serum, but not tissue CyPA is increased in UC, rather than in CD patients, compared to the control. The increase correlated with higher tissue concentration of MMP-9 and TNF-α, especially in the UC group. Moreover, we observed significantly higher level of TIMP-1/MMP-9 in UC and CD group, which overlapped with the change in MMP-9. There was no change in TIMP-2/MMP-9 in the analyzed groups. The current study suggests that serum CyPA may be an independent additional marker of IBD, especially of UC. Higher CyPA level may be followed by increased MMP-9 in those patients. However, further studies are necessary to verify the role of CyPA in IBD development.

Association between psychological measures with inflammatory anddisease-related markers of inflammatory bowel disease

Objective: This study aimed at investigating the associations between inflammatory mediators, symptoms and psychological disturbances in inflammatory bowel disease (IBD) patients.Methods: IBD patients and patient controls were examined during a single visit to a gastroenterology clinic. Disease activity was assessed using the Mayo index for ulcerative colitis (UC), inflammatory bowel disease questionnaire (IBDQ), Crohn’s disease activity index (CDAI) and Crohn’s disease endoscopic index of severity (CDEIS). Gene expression of inflammatory mediators were measured in intestinal biopsies and whole blood samples along with circulating concentrations of interleukin (IL)-6, interferon (IFN)γ, C-reactive protein (CRP), kynurenine and tryptophan. Validated depression, anxiety and quality of life scores were used to assess psychological well-being.Results: Patients who were symptomatic had the highest depression and anxiety scores, together with increased intestinal expression of IL-1β, IL-6 and matrix metalloproteinase-9, increased circulating IL-6 and CRP, and an increased circulating kynurenine:tryptophan ratio. Increased Hamilton depression (HAM-D) scores in IBD patients were observed independent of the psychological impact of acute symptoms.Conclusions: Active IBD is associated with symptoms of depression and anxiety and with a raised circulating inflammatory mediator profile. Patients with active IBD exhibiting psychological symptoms should undergo psychological evaluation to ensure the psychological aspects of the condition are considered and addressed.

Clinical application prospects of serum markers for inflammatory bowel disease

Clinical application prospects of serum markers for inflammatory bowel disease