scholarly journals Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease

2021 ◽  
pp. 203-211
Author(s):  
Hao-Hua Wang ◽  
Wan-Ying Luo ◽  
Min Lin ◽  
Xiao-Jing Li ◽  
Guang-Da Xiang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Early Stage ◽  
Reactive Hyperemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Model Assessment ◽  
Healthy Individuals ◽  
Brachial Artery Diameter ◽  
Inflammatory Bowel

Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like 4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate. Compare with healthy individuals, plasma CCDC80, erythrocyte sedi¬mentation rate (ESR), C-reactive protein (CRP) levels and homeostasis model assessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin, ANGPTL4 levels and FMD were significantly lower in both UC and CD patients (p < 0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p < 0.05), while plasma asprosin and ANGPTL4 levels were lower (pP < 0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p < 0.05), UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p < 0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p < 0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD.

Abstract 17268: ApoA-I Mimetic Peptide 4F Suppresses the Elevation of Pro-Inflammatory Lipid Mediators in Mouse Models of Inflammatory Bowel Disease

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
David Meriwether ◽  
Carmen Volpe ◽  
Victor Grijalva ◽  
Ellen O’Connor ◽  
Nasrin Dorreh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Mouse Models ◽  
Inflammatory Mediators ◽  
Bowel Disease ◽  
Ex Vivo ◽  
Early Stage ◽  
Lipid Mediators ◽  
Serosal Side ◽  
Ussing Chambers ◽  
Inflammatory Bowel

Introduction: Inflammatory bowel disease (IBD) has been linked to an increased prevalence of early stage vascular disease. ApoA-I mimetic peptides including 4F are potential therapeutic agents for the treatment of inflammatory diseases including atherosclerosis, and their mechanism of action appears localized to the intestine. We have reported that 4F protects against the development of disease in both the piroxicam-accelerated IL10-/- and myeloid COX2-/- mouse models of IBD. Hypothesis: We previously reported that plasma and lesion levels of oxidized products of linoleic and arachidonic acid correlate with disease in mouse models of atherosclerosis, and that 4F protects against disease in these models while inhibiting accumulation of these pro-inflammatory mediators. We thus sought to determine the complete lipid pro-inflammatory mediator profiles of both the COX2- and IL10-dependent models of IBD, while also determining the effect of 4F on the pro-inflammatory lipid profiles. Methods: We developed and validated a LC-ESI-MS/MS method for determining the levels of 40 lipid inflammatory mediators in both intestinal tissue and plasma, and we analyzed the effects of both disease and 4F upon these mediators in both IBD models. We also employed Ussing chambers to investigate ex vivo the direct effect of 4F on the clearance of pro-inflammatory lipid mediators from intestinal explants and serosal-side lipoproteins. Results: Disease in both models correlated with significantly elevated tissue and plasma levels of multiple lipid pro-inflammatory mediators, while the protective effects of 4F correlated with the significant suppression of most of these mediators. Of interest, 4F inhibited the disease dependent increase of 15HETE, 12HETE, 5HETE, 13HODE, LTB4, 6ketoPGF1α, PGF2α, and TXB2 in the COX2-/- model; and 15HETE, 12HETE, 13HODE, LTB4, and LTE4 in the IL10-/- model. Ex vivo, we showed that 4F could directly clear the pro-inflammatory mediators from inflamed intestinal explants, while also mediating their trans-intestinal efflux from serosal-side lipoproteins. Conclusions: 4F appears to protect against IBD in part by inhibiting the accumulation of pro-inflammatory lipid mediators, through a mechanism that involves the intestinal clearance of these mediators from tissue and plasma.

scholarly journals The Clinical Accuracy of the BÜHLMANN fCAL ELISA in the Differentiation of Inflammatory Bowel Disease From Irritable Bowel Syndrome: A Multicenter Prospective Case–Control Study

2019 ◽  
Vol 1 (3) ◽  
Author(s):  
Jeffrey A Berinstein ◽  
Calen A Steiner ◽  
Athos Bousvaros ◽  
Felix P Tiongco ◽  
Eugene Greenberg ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Irritable Bowel Syndrome ◽  
Bowel Disease ◽  
Case Control Study ◽  
Case Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Bowel ◽  
Irritable Bowel ◽  
Control Study ◽  
Prospective Case Control Study

Abstract Background Fecal calprotectin (fCAL) is a noninvasive biomarker used to differentiate between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). Methods A multicenter prospective case–control study evaluating the BÜHLMANN fCAL enzyme-linked immunosorbent assay (ELISA) was conducted in 478 subjects. Sensitivity, specificity, predictive values, and area under the receiver operator characteristic (AuROC) curve are reported and compared to another device. Results In differentiating IBD from IBS, the BÜHLMANN fCAL ELISA is very sensitive (93.3%) at a cutoff &lt;80 μg/g and balanced sensitivity (84.4%) and specificity (85.4%) at a cutoff &gt;160 μg/g (AuROC 0.933). Conclusions The BÜHLMANN fCAL ELISA demonstrates excellent discriminating between IBD and IBS.

scholarly journals Inflammatory bowel disease-associated ubiquitin ligase RNF183 promotes lysosomal degradation of DR5 and TRAIL-induced caspase activation

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yan Wu ◽  
Yuka Kimura ◽  
Takumi Okamoto ◽  
Koji Matsuhisa ◽  
Rie Asada ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Ubiquitin Ligase ◽  
Bowel Disease ◽  
Early Stage ◽  
Caspase 8 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Death Receptor 5 ◽  
Caspase Activation ◽  
Lysosomal Degradation ◽  
Inflammatory Bowel

AbstractRNF183 is a ubiquitin ligase containing RING-finger and transmembrane domains, and its expression levels are increased in patients with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, and in 2,4,6-trinitrobenzene sulfonic acid-induced colitis mice. Here, we further demonstrate that RNF183 was induced to a greater degree in the dextran sulfate sodium (DSS)-treated IBD model at a very early stage than were inflammatory cytokines. In addition, fluorescence-activated cell sorting and polymerase chain reaction analysis revealed that RNF183 was specifically expressed in epithelial cells of DSS-treated mice, which suggested that increased levels of RNF183 do not result from the accumulation of immune cells. Furthermore, we identified death receptor 5 (DR5), a member of tumour necrosis factor (TNF)-receptor superfamily, as a substrate of RNF183. RNF183 mediated K63-linked ubiquitination and lysosomal degradation of DR5. DR5 promotes TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis signal through interaction with caspase-8. Inhibition of RNF183 expression was found to suppress TRAIL-induced activation of caspase-8 and caspase-3. Thus, RNF183 promoted not only DR5 transport to lysosomes but also TRAIL-induced caspase activation and apoptosis. Together, our results provide new insights into potential roles of RNF183 in DR5-mediated caspase activation in IBD pathogenesis.

scholarly journals Anti-TNF-α Monoclonal Antibody Therapy Improves Anemia through Downregulating Hepatocyte Hepcidin Expression in Inflammatory Bowel Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Weigang Shu ◽  
Zhi Pang ◽  
Chunjin Xu ◽  
Jian Lin ◽  
Gengfeng Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Iron Metabolism ◽  
Bowel Disease ◽  
Caspase 3 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Anemia Of Chronic Disease ◽  
Hepcidin Expression ◽  
Serum Hepcidin ◽  
Inflammatory Bowel

Anemia is one of the most common complications in patients with inflammatory bowel disease (IBD). Hepcidin as a key regulator of iron metabolism is pivotal in mediating the occurrence of anemia of chronic disease. Herein, we analyzed the levels of hepcidin in sera from IBD patients by enzyme-linked immunosorbent assay and investigated its potential role in regulating the anemia in IBD. We observed that the levels of serum hepcidin were increased in active IBD patients compared with those in remitted IBD patients and healthy controls and that serum hepcidin was associated with disease activity, CRP, and ESR, respectively. Importantly, we found that the increased levels of serum hepcidin were positively correlated with the severity of anemia and the imbalance of iron metabolism in anemic UC and CD patients. Proinflammatory factors (e.g., IL-6, IL-17, and TNF-α) were positively correlated with the concentrations of serum hepcidin in IBD patients. Interestingly, hepcidin was found to be decreased in patients with Crohn’s disease after successful therapy with anti-TNF-α mAb (i.e., infliximab), indicating the underlying association between TNF-α and hepcidin expression. To investigate the specific mechanisms involved, we cultured LO2 and HepG2 cell lines in vitro under stimulation with TNF-α and observed that the levels of hepcidin mRNA were markedly upregulated in caspase-3/8- and NF-κB-dependent manners. Therefore, our data suggest that TNF-α stimulates the expression of hepcidin in IBD patients, resulting in aggravated anemia and that blockage of TNF-α or the caspase-3/8 and NF-κB pathways could downregulate hepcidin expression. This study provides inspiration for the therapy and management of anemia in IBD.

scholarly journals Expression of interleukin 1β and interleukin 1β converting enzyme by intestinal macrophages in health and inflammatory bowel disease

Gut ◽  
1998 ◽  
Vol 42 (2) ◽  
pp. 214-219 ◽  
Author(s):  
M E McAlindon ◽  
C J Hawkey ◽  
Y R Mahida
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Colonic Mucosa ◽  
Peripheral Blood Monocyte ◽  
Interleukin 1Β ◽  
Enzyme Linked Immunosorbent Assay ◽  
Normal Colonic Mucosa ◽  
Converting Enzyme ◽  
Inflammatory Bowel ◽  
Targeted Inhibition

Background—In the lipopolysaccharide (LPS) stimulated peripheral blood monocyte, the precursor form of interleukin 1β (IL-1β, 31 kD) is processed by IL-1β converting enzyme (ICE) to the mature, bioactive form (17 kD). IL-1β is a proinflammatory cytokine which is likely to have a role in the pathogenesis of inflammatory bowel disease (IBD).Aims—To investigate the expression and processing of IL-1β and ICE by tissue macrophages from normal and IBD colonic mucosa.Methods—Mucosal biopsy specimens and lamina propria cells from normal and IBD colons were studied by reverse transcription polymerase chain reaction (RT-PCR), western blot analysis, and ELISA (enzyme linked immunosorbent assay).Results—Normal colonic macrophages synthesised only the precursor form of IL-1β whereas in IBD the mature form was also produced. Similarly, cells from normal colonic mucosa synthesised ICE as the precursor (p45) only, whereas macrophages from IBD colons produced active (p20) ICE. Ac-Tyr-Val-Ala-Asp-CHO, a specific peptide aldehyde inhibitor of ICE, significantly reduced the amount of mature IL-1β released by isolated IBD macrophages (from a median of 1.2 (range 0.78–4.42) ng/ml to 0.43 (0.21–1.6) ng/ml; p<0.01).Conclusions—Exposure of normal colonic macrophages to LPS only induces the production of the precursor form of IL-1β, because the cells fail to activate ICE. In contrast, IBD colonic macrophages are able to activate ICE and hence release mature IL-1β in a manner similar to circulating monocytes. This is consistent with IBD macrophages being recently recruited from the circulating monocyte population. Targeted inhibition of ICE may represent a novel form of therapy in IBD.

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

2015 ◽  
Vol 2015 ◽  
pp. 1-4 ◽  
Author(s):  
Zehra Betül Paköz ◽  
Cem Çekiç ◽  
Mahmut Arabul ◽  
Elif Sarıtaş Yüksel ◽  
Serkan İpek ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Disease Activity ◽  
Bowel Disease ◽  
Active Phase ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Inflammatory Bowel ◽  
The Mean

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 were3837±1436and3752±1274 pg/mL, respectivelyP=0.613. The mean hepcidin serum levels in ulcerative colitis (UC) patients in remission and in the active phase were4285±8623and3727±1176 pg/mL, respectivelyP=0.241. Correlation analysis between inflammatory markers and hepcidin serum levels indicated that there was no correlation between hepcidin levels and IL-6P=0.582or CRPP=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.

scholarly journals Uncoupling of mucosal gene regulation, mRNA splicing and adherent microbiota signatures in inflammatory bowel disease

Gut ◽  
2016 ◽  
Vol 66 (12) ◽  
pp. 2087-2097 ◽  
Author(s):  
Robert Häsler ◽  
Raheleh Sheibani-Tezerji ◽  
Anupam Sinha ◽  
Matthias Barann ◽  
Ateequr Rehman ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Bowel Disease ◽  
Healthy Individuals ◽  
Transcript Levels ◽  
Molecular Approaches ◽  
Human Inflammatory Bowel Disease ◽  
Tissue Differences ◽  
Inflammatory Bowel

ObjectiveAn inadequate host response to the intestinal microbiota likely contributes to the manifestation and progression of human inflammatory bowel disease (IBD). However, molecular approaches to unravelling the nature of the defective crosstalk and its consequences for intestinal metabolic and immunological networks are lacking. We assessed the mucosal transcript levels, splicing architecture and mucosa-attached microbial communities of patients with IBD to obtain a comprehensive view of the underlying, hitherto poorly characterised interactions, and how these are altered in IBD.DesignMucosal biopsies from Crohn's disease and patients with UC, disease controls and healthy individuals (n=63) were subjected to microbiome, transcriptome and splicing analysis, employing next-generation sequencing. The three data levels were integrated by different bioinformatic approaches, including systems biology-inspired network and pathway analysis.ResultsMicrobiota, host transcript levels and host splicing patterns were influenced most strongly by tissue differences, followed by the effect of inflammation. Both factors point towards a substantial disease-related alteration of metabolic processes. We also observed a strong enrichment of splicing events in inflamed tissues, accompanied by an alteration of the mucosa-attached bacterial taxa. Finally, we noted a striking uncoupling of the three molecular entities when moving from healthy individuals via disease controls to patients with IBD.ConclusionsOur results provide strong evidence that the interplay between microbiome and host transcriptome, which normally characterises a state of intestinal homeostasis, is drastically perturbed in Crohn's disease and UC. Consequently, integrating multiple OMICs levels appears to be a promising approach to further disentangle the complexity of IBD.

scholarly journals P295 Comparative Assessment of Infliximab Trough Levels between Point-of-Care Testing and current Standard of Care (enzyme linked immunosorbent assay) in patients with Inflammatory Bowel Disease

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S325-S325
Author(s):  
D Maniero ◽  
G Lorenzon ◽  
I Marsilio ◽  
A Rigo ◽  
R Cardin ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Whole Blood ◽  
Point Of Care ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Collection ◽  
Point Of Care Testing ◽  
Deming Regression ◽  
Inflammatory Bowel ◽  
Trough Levels

Abstract Background Infliximab (IFX) is a monoclonal antibody that targets cytokine tumor necrosis factor; it is used for the treatment of patients with active inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). IFX induces and maintains remission and mucosal healing in patients with IBD. Measurement of trough levels (TL) of IFX is important to assess if the drug is within its therapeutic concentrationand to explain lack/loss of response. Standard laboratory tests to assess IFX trough levels (enzyme linked immunosorbent assays, ELISA) present some downsides, related to the long turnaround (about 3 hours), and the need of specialized equipment and laboratory personnel. For this reason, point-of care testing (POCT) was developed to provide results within a few minutes from blood collection, leading to a decision-making approach. Aim To determine the degree of analytical correlation between a recently developed POCT (ProciseDx) IFX assay which analyze capillary whole blood and the comparative ELISA from serum. Methods From October 2020 to January 2021, patients (aged≥18 years) taking IFX were recruited at Gastroenterology Unit, Padua University Hospital. In each patient, IFX levels from capillary whole blood collected by finger stick were performed using the ProciseDx IFX assay with reportable range between 1.7-77.2 µg/mL; at the same time, a serum sample from venous blood was collected to carry out Grifols’ Promonitor ELISA test (range 0.035–14.4 µg/mL). A Deming regression test was used to identify the correlation between the two methods. Results Eighty-seven patients were enrolled (63% males; mean age of 44±16), with 52% of them having CD, 45% UC and 3% an undetermined-Inflammatory Bowel Disease. The assessment with ProciseDx POCT was feasible in each patient and only in three cases blood collection from finger prick was repeated. Moreover, from blood collection to results we needed about 3±0.5 minutes, while serum ELISA analysis required the collection of at least 40 samples (around three weeks at our centre) and 3 hours to be performed. 39 patients (59% males; mean age of 44±16) had TL as assessed by ProciseDx IFX assay lower than 1.7 or greater than 14.4 µg/mL, in accordance with ELISA assessment. Among the remaining 48 patients (67% males with mean age of 45±17), The correlation between the two tests was high (the total results showed an R squared of 0.691 (95% CI 0.717-0.902). Conclusion The ProciseDx POCT has good accuracy but was more rapid and easy to be performed in providing the results of Therapeutic Drug Monitoring in outpatients taking IFX. This could lead to a more effective optimization of the biological drug, thus avoiding treatment failure.

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