OC.13.2 Prevalence and Clinical Significance of Antibodies Anti-Ifi 16 in Inflammatory Bowel Diseases (original) (raw)
Biological markers in inflammatory bowel disease: Practical consideration for clinicians
Gastroenterologie Clinique Et Biologique - GASTROEN CLIN BIOL, 2009
The biomarkers are important in the Inflammatory Bowel Disease (IBD) to gain an objective measurement of disease activity and severity, as well as prognostic indicator and outcome of therapy. And they can be helpful to avoid invasive procedures. The ideal biomarker does not exist for IBD and it is likely that more than one biomarker will be needed. Biological markers potentially useful in IBD include acute-phase proteins, fecal markers, several antibodies and novel genetic determinants. The C-reactive protein (CRP) is the most studied and has been shown to be an objective marker of inflammation. CRP is a good marker of measuring disease activity in Crohn's disease (CD) and its levels can be used to guide therapy. The fecal markers (calprotectin and lactoferrin) may be helpful in differentiating patients with IBD from those with functional disorders and to predict clinical relapse. The panel of serologic markers (anti-Saccharomyces cerevisiae antibody, perinuclear anti-neutrophil cytoplasmic antibody, anti-OmpC and anti-I2 and antiglycan antibodies) for IBD can be used to stratify IBD patients into more homogeneous subgroups with respect to disease progression. Correlating serologic markers with genotypes and clinical phenotypes should enhance our understanding of the pathophysiology of IBD. The development of biomarkers in IBD will be very important in the future with the increasing utilization of novel methodological approaches like genomics and proteomics.Le rôle des marqueurs biologiques est important dans les maladies inflammatoires chroniques intestinales (MICI), à la fois pour essayer de mesurer objectivement l’activité et de la sévérité de la maladie, comme indicateurs pronostiques, ou encore pour évaluer la réponse au traitement. Ils sont aussi susceptibles d’éviter de réaliser des examens complémentaires invasifs. Dans les MICI, le biomarqueur idéal n’existe pas, et plusieurs marqueurs utilisés au même moment sont souvent nécessaires. Les marqueurs potentiellement utiles sont les protéines inflammatoires, des marqueurs fécaux, certains anticorps (sérologies), ainsi éventuellement que de nouveaux marqueurs génétiques. La protéine C-réactive (CRP) a été la plus étudiée. C’est est un marqueur objectif de l’état inflammatoire, corrélé à l’activité de la maladie dans la maladie de Crohn, et aidant parfois à guider son traitement. Les marqueurs fécaux (calprotectine et lactoferrine) peuvent être utiles pour différencier les MICI de malades ayant un trouble fonctionnel intestinal, et sont susceptibles de prédire le risque de rechute. L’éventail des sérologies disponibles (anticorps anti-Saccharomyces cerevisiae, anti-cytoplasme des polynucléaires neutrophiles de localisation péri-nucléaire, anti-OmpC, anti-I2, et anti-glycanes) peuvent être utilisés pour essayer de mieux stratifier les MICI dans des sous-groupes plus homogènes concernant leur profil évolutif. Leur corrélation avec les caractéristiques génotypiques et le phénotype clinique des malades devrait améliorer la compréhension de la physiopathologie des MICI. Il est enfin possible que l’utilisation croissante à l’aide d’outils de génomique et/ou de protéomique fonctionnelle de plus en plus performants, permette l’identification de nouveau biomarqueurs d’intérêt dans les MICI.
PLOS ONE, 2015
Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.
A simple method for assessing intestinal inflammation in Crohn's disease
Gut, 2000
Background and aims-Assessing the presence and degree of intestinal inflammation objectively, simply, and reliably is a significant problem in gastroenterology. We assessed faecal excretion of calprotectin, a stable neutrophil specific marker, as an index of intestinal inflammation and its potential use as a screening test to discriminate between patients with Crohn's disease and those with irritable bowel syndrome.
Journal of Research in Medical Sciences, 2012
BACKGROUND: Symptoms consistent with irritable bowel syndrome (IBS) are common among patients with inflammatory bowel disease (IBD) in remission phase, and clinicians have difficulties in interpreting such symptoms as an ongoing disease activity or a coexistent IBS. We investigated if the assessment of fecal calprotectin (FC) could be helpful in this regard. METHODS: The study population consisted of 42 IBD patients in remission that fulfilled the IBS diagnostic criteria (Rome III), 24 IBS patients and 30 healthy controls. Clinical remission was determined based on physician's assessments, not using corticosteroids or biological agents within the preceding six months and activity indices. The FC and C-reactive protein (CRP) levels were investigated and compared among the groups. RESULTS: FC levels were significantly higher in patients with IBD (142.9 ± 216.5 µg/g) than those with IBS (24.9 ± 27.8 µg/g) and controls (17.9 ± 14.8 µg/g) (p < 0.001). CRP levels were also higher in IBD than IBS patients [3.9 (SE = 0.5) vs. 2.1 (SE = 0.5), p = 0.030]. However, FC levels were not significantly correlated with CRP levels or with severity of symptoms in IBD and IBS patients (p > 0.05). CONCLUSIONS: The presence of IBS-like symptoms in IBD patients in clinical remission may reflect an ongoing activity of IBD, which is undetectable by current activity indices. Serum CRP levels are not specific enough in such situation, and FC is a more accurate and specific test for investigating mucosal inflammation in this regard.
311 Large Scale Validation of a Biomarker for Diarrhea-Predominant Irritable Bowel Syndrome
Gastroenterology, 2015
Diarrhea-predominant irritable bowel syndrome (IBS) is diagnosed through clinical criteria after excluding "organic" conditions, and can be precipitated by acute gastroenteritis. Cytolethal distending toxin B (CdtB) is produced by bacteria that cause acute gastroenteritis, and a post-infectious animal model demonstrates that host antibodies to CdtB cross-react with vinculin in the host gut, producing an IBS-like phenotype. Therefore, we assessed circulating anti-CdtB and anti-vinculin antibodies as biomarkers for D-IBS in human subjects. Subjects with D-IBS based on Rome criteria (n=2375) were recruited from a large-scale multicenter clinical trial for D-IBS (TARGET 3). Subjects with inflammatory bowel disease (IBD) (n=142), subjects with celiac disease (n=121), and healthy controls (n=43) were obtained for comparison. Subjects with IBD and celiac disease were recruited based on the presence of intestinal complaints and histologic confirmation of chronic inflammatory changes in the colon or small intestine. Subjects with celiac disease were also required to have an elevated tTG and biopsy. All subjects were aged between 18 and 65 years. Plasma levels of anti-CdtB and anti-vinculin antibodies were determined by ELISA, and compared between groups. Anti-CdtB titers were significantly higher in D-IBS subjects compared to IBD, healthy controls and celiac disease (P<0.001). Anti-vinculin titers were also significantly higher in IBS (P<0.001) compared to the other groups. The area-under-the-receiver operating curves (AUCs) were 0.81 and 0.62 for diagnosis of D-IBS against IBD for anti-CdtB and anti-vinculin, respectively. Both tests were less specific in differentiating IBS from celiac disease. Optimization demonstrated that for anti-CdtB (optical density2.80) the specificity, sensitivity and likelihood ratio were 91.6%, 43.7 and 5.2, respectively, and for anti-vinculin (OD1.68) were 83.8%, 32.6 and 2.0, respectively. These results confirm that anti-CdtB and anti-vinculin antibodies are elevated in D-IBS compared to non-IBS subjects. These biomarkers may be especially helpful in distinguishing D-IBS from IBD in the workup of chronic diarrhea.
Challenges in IBD Research: Preclinical Human IBD Mechanisms
Inflammatory Bowel Diseases, 2019
Preclinical human IBD mechanisms is part of five focus areas of the Challenges in IBD research document, which also include environmental triggers, novel technologies, precision medicine and pragmatic clinical research. The Challenges in IBD research document provides a comprehensive overview of current gaps in inflammatory bowel diseases (IBD) research and delivers actionable approaches to address them. It is the result of a multidisciplinary input from scientists, clinicians, patients, and funders, and represents a valuable resource for patient centric research prioritization. In particular, the preclinical human IBD mechanisms manuscript is focused on highlighting the main research gaps in the pathophysiological understanding of human IBD. These research gap areas include: 1) triggers of immune responses; 2) intestinal epithelial homeostasis and wound repair; 3) age-specific pathophysiology; 4) disease complications; 5) heterogeneous response to treatments; and 6) determination of disease location. As an approach to address these research gaps, the prioritization of reverse translation studies is proposed in which clinical observations are the foundation for experimental IBD research in the lab, and for the identification of new therapeutic targets and biomarkers. The use of human samples in validating basic research findings and development of precision medicine solutions is also proposed. This prioritization aims to put emphasis on relevant biochemical pathways and humanized in vitro and in vivo models that extrapolate meaningfully to human IBD, to eventually yield first-in-class and effective therapies.
Revista de Gastroenterología del Perú
Background: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. Objective: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. Materials and methods: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. Results: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. ...
• Although several studies propose that routine screening for celiac disease (CD) in subjects with irritable bowel syndrome (IBS) (specifically IBS-D and IBS-M) is justified, recent studies have shown controversial results in relation to this theme. • In this large case–control study (n = 800) using a control population paired by age and sex and a strategy of multiple antibodies (and their combinations) with histologic confirmation, we found that the OR for detecting CD in subjects with IBS was 5.21. • The IBS-D subtype had the highest prevalence of positivity for h-tTG IgA and DGP II IgA, compared with the other subgroups. • According to the multivariable analysis, neither sex, age nor the length of time of symptom progression was associated with an increased risk for CD. Abstract Background The cost-effectiveness for screening for celiac disease (CD) in patients with irritable bowel syndrome (IBS), specifically in the diarrhea (IBS-D) subtype, is beneficial if the prevalence is >1%. However , recent studies have shown controversial results. In this large case–control study, our aim was to determine the prevalence of CD and a panel of related antibodies in patients diagnosed with IBS. Materials and methods Four hundred IBS patients (Rome III) and 400 asymptomatic healthy controls were prospectively evaluated using antihuman tissue transglutam-inase (h-tTG IgA) and deamidated gliadin peptide antibodies (DGP II IgA and DGP II IgG). Duodenal biopsy was performed on the patients that were positive for the h-tTG IgA and/or DGP II IgG anti-bodies. Results The mean age of the population was 44.47 AE 18.01 years and 335 (82%) of the subjects were women. Twenty-one patients and six controls had at least one positive test for CD (5.25% VS 1.5%, p = 0.003, OR 3.63 [95% CI 1.4–9.11]). Eighteen patients were positive for h-tTG and/or DGP-II IgG. Histologic confirmation of CD was 2.5% in the IBS patients vs 0.5% in the controls (p = 0.04, OR 5.21).