Soluble adhesion molecules in inflammatory bowel disease

Impaired iron absorption or increased loss of iron was found to correlate with disease activity and markers of inflammation in inflammatory bowel disease (IBD). Red cell distribution width (RDW) could be a reliable index of anisocytosis with the highest sensitivity to iron deficiency. The importance of RDW in assessment of IBD disease activity is unknown. In this study, we aimed to determine if RDW could be useful in detecting active disease in patients with IBD. A total of 74 patients with ulcerative colitis (UC) and 22 patients with Crohn's disease (CD) formed the study group with 20 age- and sex-matched healthy volunteers as the control group. CD activity index higher than 150 in patients with CD was considered to indicate active disease. Patients with moderate and severe disease according to the Truelove-Witts scale were accepted as having active UC. In addition to RDW, serum C-reactive protein (CRP) and fibrinogen levels, erythrocyte sedimentation rates (ESR), leukocyte, and platelet counts were measured. Fourteen (63.6%) of the patients with CD and 43 (58.1%) of the patients with UC had active disease. RDW, fibrinogen, CRP, ESR, and platelet counts were all significantly elevated in patients having active IBD compared with those without active disease and controls (P < 0.05). The study subjects were further classified into two subgroups: cases with active and inactive UC and those with active and inactive CD. A subgroup analysis indicated that for an RDW cutoff of 14, the sensitivity for detecting active UC was 88% and the specificity was 71% (area under curve [AUC] 0.81, P = 0.0001). RDW was the most sensitive and specific parameter indicating active UC. However, the same was not true for CD since CRP at a cutoff of 0.54 mg/dl showed a sensitivity of 92% and a specificity of 63% (AUC 0.92, P = 0.001), whereas RDW at a cutoff of 14.1 showed 78% sensitivity and 63% specificity to detect active CD. Among the laboratory tests investigated, including fibrinogen, CRP, ESR, and platelet counts, receiver operating characteristic (ROC) curve analysis indicated RDW to be the most significant indicator of active UC. For CD, CRP was an important marker of active disease.

Single-Cell Analyses of Colon and Blood Reveal Distinct Immune Cell Signatures of Ulcerative Colitis and Crohn’s Disease

Cytokines serve a central function as key factors in the regulation of the intestinal immune response and mediation of tissue damage in inflammatory bowel disease (IBD). Abnormalities in the expression of immunoregulatory cytokines such as IL-2, IL-4, IL-10 and interferon-gamma (IFN-gamma) may indicate a dysregulation of intestinal immunity probably associated with pathogenic events. Therefore, cytokine mRNA concentrations were determined in the mucosa of patients with IBD at sites of active (n = 13) and inactive (n = 12) ulcerative colitis (UC), active (n = 11) and inactive (n = 11) Crohn's disease (CD) and in control patients (n = 14) using quantitative RT-PCR. IL-10 mRNA concentrations were significantly increased in patients with both active UC (P < 0.001) and active CD (P < 0.005) compared with control patients. IFN-gamma mRNA concentrations were also significantly increased both in patients with active UC (P < 0.02) and active CD (P < 0.05) compared with control patients, whereas IL-2 mRNA levels were significantly (P < 0.02) increased only in active CD. IL-4 mRNA expression in the intestinal mucosa was frequently below the detection limit. Our results demonstrate that chronic intestinal inflammation in patients with CD is characterized by an increase of Th1-like cytokines. Furthermore, the increased IL-10 mRNA expression at sites of active IBD suggests that IL-10 is an important regulatory component involved in the control of the inflammatory response in inflammatory bowel disease.

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.

Fibroblast growth factor 21 (FGF21) is a stress-inducible hormone that regulates nutrient and metabolic homeostasis. Inflammatory state is one of the stimulators of FGF21 secretion. The aim of the study was to assess correlations between serum FGF21 level and inflammatory markers as well as nutritional status indicators in patients with inflammatory bowel disease (IBD). Fasting serum FGF21 level was measured using ELISA test in 105 IBD patients and 17 healthy controls. There were 31 subjects with active ulcerative colitis (UC), 16 with inactive UC, 36 with active Crohn's disease (CD), and 22 with inactive CD. Clinical and endoscopic activity of IBD was evaluated based on validated scales and indices. Fecal calprotectin, serum CRP, and selected parameters of nutritional status were tested in all patients. Serum FGF21 level was characterized by fluctuations depending on the IBD activity. FGF21 level was significantly higher in both active UC and CD compared to inactive phases of the diseases and to the controls. A correlation between FGF21 and fecal calprotectin levels was also found in UC and CD. Additionally, in CD, FGF21 level positively correlated with CRP level. In both UC and CD, a negative correlation was noted between FGF21 level and nutritional status parameters including cholesterol, protein, albumin levels, and BMI. The intensity of intestinal inflammation is related to FGF21 level, which correlates negatively with nutritional status indicators in IBD. The disturbances in FGF21 secretion may contribute to the multifactorial pathogenesis of malnutrition and weight loss in IBD patients.

T-cell activation in Crohn's disease. Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells.

Background Individuals with inflammatory bowel disease (IBD) experience mental health disorders at a rate of 1.5 to 2 times higher than the general population. With the rising incidence of IBD, many people are affected by the disease during significant life stages such as pregnancy. Research on the impact of IBD on anxiety and depression in pregnant people is limited. Aims To assess the impact of active IBD on anxiety and depression during pregnancy. Methods This retrospective survey study analyzed data from patients seen at the ‘Preconception and Pregnancy in IBD’ clinic at Mount Sinai Hospital who conceived prior to January 1st, 2022. Standardized pre-visit surveys included validated measures of mental health (General Anxiety Disorder-7 for anxiety; Patient Health Questionnaire-9 for depression) and IBD disease activity (pMayo6 for ulcerative colitis (UC); mHBI for Crohn’s disease (CD)). Demographic data was also collected (age, marital status, occupational status, smoking habits, alcohol use, cannabis use, previous diagnosis of anxiety and/or depression, IBD type, IBD surgical history, and medication use). Linear regression models were used to assess associations between disease activity and anxiety/depression, adjusting for medication type and stratified by trimester and IBD subtype. Results A total of 94 patients were included in this study, 42 patients had UC (44.7%), and 52 patients had CD (55.3%). The median age for the UC group was 32 (IQR 31-35.8), and the median age for the CD group was 32.7 (IQR 30-35.2). Active CD in the second trimester was significantly associated with higher anxiety (p = 0.024) and depression scores (p = 0.021) compared to those in remission. For CD, 6 patients (35.3%) in trimester 1, 8 patients in trimester 2 (25.8%), and 8 patients (26.7%) in trimester 3 had a GAD-7 score of ≥ 5; 5 patients (29.4%) in trimester 1, 6 patients (19.4%) in trimester 2, and 7 patients (23.3%) in trimester 3 had a PHQ-9 score of ≥ 5. Active UC in the second trimester was associated with significantly higher anxiety (p = 0.034) and depression (p = 0.022) scores compared to inactive UC. In the third trimester, this pattern persisted, with active UC again associated with elevated anxiety (p = 0.030) and depression (p = 0.027) scores. For UC, 4 patients (33.3%) in trimester 1, 9 patients (30%) in trimester 2, and 9 patients (31.0%) in trimester 3 had a GAD-7 score of ≥ 5; 4 patients in trimester 1, 4 patients in trimester 2, and 7 patients in trimester 3 had a PHQ-9 score of ≥ 5. Conclusions Active IBD during pregnancy is significantly associated with increased anxiety and depression, therefore, a multidisciplinary approach including mental health support is imperative for pregnant people with IBD. Funding Agencies None

INTRODUCTION: Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications in the United States. Some recent studies have suggested that PPIs may have a negative effect on the gut microbiome. Dysbiosis of the gut microbiome has been linked with inflammatory bowel disease (IBD). We hypothesized that PPI use is associated with increased IBD flares and activity. This study was aimed to assess the effect of PPIs on IBD flares and activity. METHODS: We conducted a prospective longitudinal study of Veterans from the IBD clinic at the Michael E. DeBakey VA Medical Center from 2014 to 2018. Our eligibility criteria included patients who were at least 18 years of age, who were diagnosed with Crohn's Disease (CD) or Ulcerative Colitis (UC), and who had at least 1 clinic visit. IBD flare was defined by patient self-report of IBD flare between clinical encounters. IBD activity was quantified using the partial Mayo Score (pMayo) for UC, and the Harvey Bradshaw Index (HBI) for CD. Remission was defined by pMayo &lt;2 for UC and HBI &lt;5 for CD. Exposure of PPI was confirmed by chart review. Associations of PPI use with IBD flare and activity were assessed using T-tests and Chi-squared tests. RESULTS: A total of 132 patients were included in the analysis of which 74 had CD and 58 had UC. 40 patients were PPI users, and IBD flares occurred in 60 patients. No significant association between PPI usage and IBD flares were observed: 42.5% of PPI users developed flares compared to 46.7% of non-PPI users who developed flares, P-value = 0.658. In patients with CD, PPI use was associated with non-remission status (RR 2.53; 95% CI 1.04-6.15). In UC patients, PPI use was not associated with non- remission status (RR 1.10; 95% CI 0.67-1.79). 13 CD patients on PPIs discontinued the PPI between encounters, which was associated with a statistically significant decrease in HBI (3.62- &gt;2.54, P-value = 0.005). Among UC patients who discontinued PPIs, there was a non-significant trend towards decreased pMayo (2.26- &gt;1.59, P-value = 0.069). CONCLUSION: Amongst CD patients, PPI use was not associated with interval flare however, it was associated with non-remission status. Cessation of PPIs was associated with a statistically significant decrease in HBI in CD patients. In UC patients, no significant association between PPI use and flare or activity were observed. Decreasing unnecessary PPI use in patients with CD may decrease disease severity.

Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for monitoring disease activity in inflammatory bowel disease (IBD). The aim of this study was to evaluate its utility in monitoring disease activity. In this retrospective study based on case records between August 2020 and July 2021 at our two centers, we examined the correlation between serum levels of LRG and C-reactive protein (CRP) with disease activity in IBD patients. Background factors related to serum LRG levels were also analyzed. Overall, 47 Crohn's disease (CD) and 123 ulcerative colitis (UC) patients were evaluated. In patients with CD, LRG and CRP levels correlated with Harvey-Bradshaw Index (HBI) and Simple Endoscopic Score for CD (SES-CD) (LRG and HBI, r = 0.397; LRG and SES-CD, r = 0.637; CRP and HBI, r = 0.253; CRP and SES-CD, r = 0.332). In patients with UC, LRG and CRP significantly correlated with the partial Mayo score (PMS) and Mayo endoscopic subscore (MES) (LRG and PMS, r = 0.3; CRP and PMS, r = 0.282; LRG and MES, r = 0.424; CRP and MES, r = 0.459). In CD patients with normal CRP, serum LRG level was significantly higher in those with mucosal inflammation than in those with mucosal healing (16.4 vs. 10.7 μg/ mL). Stenosis was associated with serum LRG levels in CD group using multiple regression analysis. Therefore, LRG is a useful biomarker for monitoring disease activity and mucosal inflammation, and indicates the status of intestinal stenosis in IBD patients.

Background IBD has been recognized as a systemic inflammatory entity and as such, it is anticipated to induce changes exceeding the boundaries of bowel mucosa, being reflected in a broader spectrum of tissues, including blood. Calgranulin c is a calcium binding protein with proinflammatory properties. It has been associated with different diseases of inflammatory origin, including inflammatory bowel disease (IBD). In our present study, the utility of serum calgranulin c as marker for inflammatory bowel disease was tested. Objective is to evaluate the role of serum calgranulin c as a diagnostic and prognostic marker in IBD patients and to correlate it's level with different biochemical, endoscopic and clinical parameters. Patients and Methods Calgranulin c serum levels were determined in 50 patients with ulcerative colitis (UC), 20 patients with Crohn’s disease (CD) and 73 with functional bowel disorder (IBS). Calgranulin c serum concentrations were analysed using double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to assay the level of Human S100 Calcium Binding Protein A12(S100A12) in samples. Results In the present study we found that the mean serum calgranulin c were 723.640±529.055 ng/ml (range: 63-2000) in UC, 759.233±797.963 ng/ml (range: 110-2000) in CD and 80.850±24.416 ng/mL (range: 52-135) in control group. UC and CD patients had significantly higher serum calgranulin c levels compared to IBS patients with p &amp;lt; 0.001 for both. the best cut-off for serum calgranulin c levels in prediction of IBD was &amp;gt;110 ng/Ml with sensitivity 96.67%, specificity 85.00%, and test accuracy was 97.8%. best cut-off for serum calgranulin c levels in prediction of UC was &amp;gt;135 ng/mL. the best cut-off for serum calgranulin c levels in prediction of CD was &amp;gt;110 ng/Ml. Moreover, the best cut-off for serum calgranulin c levels of &amp;gt; 435 ng/mL could predict activity in UC group depend on UCEIS, depend on ACGUCAI and Erosions and ulcers in endoscopy. another cut off level of Serum calgranulin c in prediction of luminal bleeding in endoscopy in UC patients was &amp;gt;625 ng/ml. the best cut off level of Serum calgranulin c in prediction of activity among CD patients depend on CDAI was &amp;gt;437 ng/ml. Conclusion Serum calgranulin c was found to be higher in patients with IBD than with functional bowel disorded (IBS). Levels of serum calgranulin c varied significantly with disease severity in patients with UC and CD. Serum calgranulin c was found to be higher among patients with active CD and UC than those in remission. Serum calgranulin c can be used as a non invasive marker of inflammatory bowel disease. It can distinguish IBD from IBS and can be considered as a maker of activity in IBD patients.

Inflammatory bowel disease (IBD), which consists of Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder of the intestine. The etiology is heterogeneous and multifactorial, including genetic susceptibility, immune-mediated tissue damage, and changes of lumen microenvironment, especially short-chain fatty acid (SCFA) producing bacteria. Several studies reported a decrease in SCFA concentration in both CD and UC. In fact, SCFAs has important roles in accelerating disease remission. This systematic review aimed to evaluate the changes in SCFA concentration, the composition of SCFA-producing bacteria, and SCFA metabolism in IBD. A literature search was conducted via PubMed, Scopus, and CENTRAL by selecting studies according to inclusion and exclusion criteria. The quality and risk of bias assessment were performed using the Newcastle-Ottawa Scale (NOS). Overall, 160 UC and 127 CD patients from 5 studies were reviewed. The SCFA concentration was significantly reduced (p &lt;0.05) in both PC and UC. Moreover, there was a decrease in major SCFA-producing bacteria. Clostridium coccoides were significantly decreased in the feces of active UC (p = 0.015) and CD (p = 0.04). Clostridium leptum was decreased on intestinal mucosal biopsy of active CD and UC (p &lt;0.0001). Faecalibacterium prausnitzii were decreased in active CD faeces (p &lt;0.0001) and UC (p = 0.0001). Butyrate oxidation rate was also reported to decrease in UC compared to control (p&lt;0.0001). In conclusion, the ability of major SCFA-producing bacterial production in IBD was diminished, which implies a decreased protective and anti-inflammatory effect of SCFA that altered its metabolism.

Neutrophil gelatinase-associated lipocalin (NGAL) is a multi-potent 25-kDa protein mainly secreted by neutrophils. In inflammatory bowel disease (IBD), overexpression of NGAL in colon epithelium has been previously shown. This is the first study analyzing serum and urinary NGAL levels in IBD patients, with regard to specific characteristics of patients and disease. Serum and urinary NGAL levels were determined in 181 patients with IBD, 93 with ulcerative colitis (UC), and 88 with Crohn's disease (CD), 82 healthy controls (HC), and 41 patients with irritable bowel syndrome (IBS). Serum NGAL levels were elevated in IBD patients (88.19 ± 40.75 ng/mL) compared with either HC (60.06 ± 24.18 ng/mL) or IBS patients (60.80 ± 20.30 ng/mL), P < 0.0001. No significant difference was shown between UC (86.62 ± 35.40 ng/mL) and CD (89.92 ± 46.05 ng/mL). Significantly higher levels of serum NGAL were observed in patients with active (120.1 ± 38.46) versus inactive IBD (61.58 ± 15.98), P < 0.0001. Serum NGAL displayed a strong ability to distinguish active IBD from inactive disease, healthy controls, or IBS patients with a sensitivity of 100, 95, and 95% and a specificity of 68, 83, and 79%, respectively, performing better than erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in the assessment of disease activity in both UC and CD. Urinary NGAL levels showed neither significant difference among patients and controls nor correlation with disease activity. Serum NGAL is elevated particularly in active IBD and correlates with established markers of inflammation and disease activity, implicating its role in the pathophysiology of IBD.

Objective To investigate the role and significance of miRNA-21 in the pathogenesis and development of inflammatory bowel disease (IBD). Methods The expressions of microRNA-21 (miRNA-21) in colonic mucosa and peripheral blood CD4+ T cells were analyzed by fluorescence quantitative polymerase chain reaction (PCR) in 26 patients with active Crohn's disease (CD), 23 patients with active ulcerative colitis (UC) and 19 healthy controls. The relative expression amount of miRNA-21 in colonic mucosal and peripheral blood CD4+ T cells in 11 patients with CD was compared before and after infliximab (IFX) treatment, and its correlation with tumor necrosis factor(TNF)-α was analyzed. t-test was performed for comparison between groups. The correlation between miRNA-21 expression in peripheral blood CD4+ T cells and serum TNF-α was analyzed by Spearman correlation analysis. Results The expression of miRNA-21 in colonic mucosa of CD patients and UC patients was 4.720±0.397 and 4.993±0.415, respectively, which were both higher than that of healthy control group (1.101±0.284), and the differences were statistically significant (t=7.657 and 8.356, both P<0.01). The expression of miRNA-21 in peripheral blood CD4+ T cells of CD patients and UC patients was 3.254±0.323 and 3.450±0.311, which were both higher than that of healthy control group (0.891±0.220), and the differences were statistically significant (t=6.007 and 7.098, both P<0.01). After 12 weeks of IFX treatment, simple endoscopic score for Crohn's disease (SES-CD) of CD patients was 8.019±0.349, which was lower than that before treatment (21.502±1.185), and the difference was statistically significant (t=10.910, P<0.01). The serum TNF-α level was 61.570±6.252, which was lower than that before treatment (173.500±12.670), and the difference was statistically significant (t=7.926, P<0.01). The results of correlation analysis indicated that serum TNF-α level was positively correlated with miRNA-21 expression in peripheral blood CD4+ T cells (r=0.780 4, P<0.01). Conclusions The increasing of miRNA-21 expression in IBD was closely correlated with the serum TNF-α level and severity of inflammation. miRNA-21 might be a new target for IBD treatment. Key words: miRNA-21; Inflammatory bowel diseases; Crohn disease; Colitis, ulcerative

P120 The concentrations of calprotectin in stool samples vary during the day in patients with active ulcerative colitis

Introduction: Vedolizumab (VDZ), a gut-selective monoclonal anti-integrin antibody, is approved for the treatment of moderate-to-severely active Crohn's disease (CD) and ulcerative colitis (UC) in adults. This study was a systematic review of recently published reports describing real-world effectiveness and safety of VDZ to date. Methods: MEDLINE-, Cochrane-, and Embase-indexed publications, and conference abstracts (n ≥10) were searched from 1 January 2014 to 27 May 2016 for studies reporting VDZ outcomes. Reports for patients < 18 years of age or of off-label VDZ use were excluded. Results: 67 reports were identified (primarily conference abstracts) describing over 7,700 VDZ patients. The majority of VDZ-treated patients had prior exposure to ≥1 anti-tumour necrosis factor (TNF) therapy. Definitions of clinical remission included partial Mayo score, simple clinical colitis activity index, Harvey-Bradshaw index, Crohn's disease activity index, and clinician assessment. In UC, real-world clinical remission rates at week 14 ranged from 24-55% (6 studies). Three UC VDZ studies reported steroid-free clinical remission rates at week 14 ranging from 19-36%. In 3 UC studies not reporting clinical remission rates, marked reductions in disease activity scores (DAIs) from baseline at week 14 were observed. Mucosal healing was observed in 57-69% of patients in 4 UC studies (Table 1). In CD, real-world clinical remission rates at week 14 ranged from 14-38% (7 studies). Three CD studies reported steroid-free clinical remission rates between 19-31% at week 14. In 5 CD studies not reporting clinical remission rates, marked reductions in DAIs from baseline at week 14 were observed. Mucosal healing was observed in 17-63% of patients in 4 CD studies (Table 1). VDZ patients experiencing adverse events (AEs) ranged from 4-42% (15 studies); rates of infection ranged from 4-13% (8 studies). Two studies reported serious AEs in 7-8% of VDZ patients (2-10% of VDZ patients experienced a serious infection).Table 1: Proportion of Vedolizumab Patients with Mucosal Healing in Ulcerative Colitis and Crohn's DiseaseConclusion: Real-world clinical effectiveness and safety data for VDZ confirm treatment benefit and a favourable safety profile for moderate-to-severely active UC and CD in largely anti-TNF-refractory populations. Evidence from larger VDZ cohorts over longer periods are required, especially in patients naive to biologic therapy.