OC.13.2 Prevalence and Clinical Significance of Antibodies Anti-Ifi 16 in Inflammatory Bowel Diseases (original) (raw)
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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.
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.
Intestinal inflammation markers in inflammatory bowel disease
International Journal Of Community Medicine And Public Health, 2018
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 fluores...
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.
Mediators of Inflammation, 2009
Intestinal alterations in IBD are triggered and maintained by an overexpression of proinflammatory cytokines. Additionally, increased immune activation has been found in the adjacent intestinal areas without displaying any apparent histological alterations, however, the regulatory environment is not well established. Biopsy specimens from patients with ulcerative colitis (UC) and Crohn's disease (CD), from both affected and unaffected areas, and also from a group of colonic biopsies from healthy controls, were included in our study. Cytokines and markers of mucosal damage were analyzed by real-time PCR, and some of the results confirmed by western-blot and ELISA. Levels of IFNγ, TNFα, IL-6, IL-15, IL-18, and IL-23 were increased (above healthy controls) in both affected and unaffected areas from IBD. IL-1β, IL-6, IL-12, and IL-27 were higher in affected areas compared to unaffected ones in UC but not CD. In general, a correlation was observed between mRNA levels of these cytokines and both iNOS and Granzyme B. SOCS-2 and SOCS-3 were also increased in the affected areas. In conclusion, the unaffected areas from IBD show increased levels of a restricted set of cytokines that may exert immune activating roles in these areas without being able to trigger tissue damage.
Scandinavian Journal of Gastroenterology, 2020
Background: It has been proposed that irritable bowel syndrome (IBS) is a low-grade mucosal inflammatory disease. Objective: To characterize the intestinal inflammatory profile in IBS patients with or without fructose intolerance. Design: Patients referred to colonoscopy with IBS complaints were screened for participation. IBS patients diagnosed according to the Rome II criteria and with no organic gastrointestinal disease were included in the study. One subgroup was patients included in a fructose-reduced diet study for 2 months with effects based on VAS symptom scores. Healthy controls were subjects under investigation of colorectal cancer screening with no IBS or other gastrointestinal diseases. All patients included had normal histology from rectum. Mucosal cytokines, chemokines and growth factors were measured by multiplex technology. Results: Of 27 inflammatory markers tested in the mucosal tissue, 13 were significantly increased and none was significantly decreased in IBS as compared to controls. Significantly increased were the proinflammatory cytokines tumor necrosis factor, the typical TH1 markers IFNc, IL-1b, IL-2 and RANTES, the typical TH2 markers IL-5 and IL-9, the TH17 marker IL-17, TNF, the pleiotropic IL-15, and the growth factors bFGF and GM-CSF. In IBS patients with fructose intolerance only IL-5 was significantly increased compared to patients without fructose intolerance. Conclusions: A dysregulated mucosal inflammatory profile with an increased level of TH1, TH2 and TH17 markers, and growth factors were observed in bowel mucosa in of IBS patients when compared to healthy controls.