New serological biomarkers of inflammatory bowel disease

Division of Gastroenterology, Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Ave, 918 Ross Research Bldg, Baltimore, MD 21205, United States.
World Journal of Gastroenterology (Impact Factor: 2.37). 10/2008; 14(33):5115-24.
Source: PubMed


Serological biomarkers in inflammatory bowel disease (IBD) are a rapidly expanding list of non-invasive tests for objective assessments of disease activity, early diagnosis, prognosis evaluation and surveillance. This review summarizes both old and new biomarkers in IBD, but focuses on the development and characterization of new serological biomarkers (identified since 2007). These include five new anti-glycan antibodies, anti-chitobioside IgA (ACCA), anti-laminaribioside IgG (ALCA), anti-manobioside IgG (AMCA), and antibodies against chemically synthesized (Sigma) two major oligomannose epitopes, Man alpha-1,3 Man alpha-1,2 Man (SigmaMan3) and Man alpha-1,3 Man alpha-1,2 Man alpha-1,2 Man (SigmaMan4). These new biomarkers serve as valuable complementary tools to existing biomarkers not only in differentiating Crohn's disease (CD), ulcerative colitis (UC), normal and other non-IBD gut diseases, but also in predicting disease involvement (ileum vs colon), IBD risk (as subclinical biomarkers), and disease course (risk of complication and surgery). Interestingly, the prevalence of the antiglycan antibodies, including anti-Saccharomyces cerevisiae antibodies (ASCA), ALCA and AMCA, was found to be associated with single nucleotide polymorphisms (SNPs) of IBD susceptible genes such as NOD2/CARD15, NOD1/CARD4, toll-like receptors (TLR) 2 and 4, and beta-defensin-1. Furthermore, a gene dosage effect was observed: anti-glycan positivity became more frequent as the number of NOD2/CARD15 SNPS increased. Other new serum/plasma IBD biomarkers reviewed include ubiquitination factor E4A (UBE4A), CXCL16 (a chemokine), resistin, and apolipoprotein A-IV. This review also discusses the most recent studies in IBD biomarker discovery by the application of new technologies such as proteomics, fourier transform near-infrared spectroscopy, and multiplex enzyme-linked immunosorbent assay (ELISA)'s (with an emphasis on cytokine/chemokine profiling). Finally, the prospects of developing more clinically useful novel diagnostic algorithms by incorporating new technologies in serological biomarker profiling and integrating multiple biomarkers with bioinformatics analysis/modeling are also discussed.

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Available from: Xuhang Li, Sep 12, 2014
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    • "Koçer et al.[28]found that the serum level of interleukin-6 (IL-6), a proinflammatory cytokine, was higher in patients with tension-type headache compared to the control group, and they discussed the effect of inflammation on the etiology of tension-type headache. Some studies found that levels of cytokines such as IL-1, IL-6, and IL-8 were higher in patients with Crohn's disease[29,30]. The higher prevalence of headache in CD group in this study may be related to the level of cytokines. However, further studies are needed to explain such a relationship since we did not evaluate the IL levels in our patient group. "
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    ABSTRACT: Objectives . This study is aimed at studying the prevalence and characteristics of different types of headaches in patients with Crohn’s disease. Materials and Methods . 51 patients in Crohn’s disease group (F/M: 26/25) and 51 patients in control group (F/M: 27/24) were involved. Patients in Crohn’s disease group were diagnosed and monitored according to European Crohn’s and Colitis Organization diagnostic criteria. The control group composed of healthy subjects with similar age and sex to Crohn’s disease group. Headache was classified using the International Headache Society II criteria. Results . Headache was reported by 35/51 (68.6%) patients in Crohn’s disease group and 21/51 (41.2%) patients in the control group. The prevalence of headache was statistically high in the group with Crohn’s disease (OR: 3.125 (95% CI: 1.38–7.04); p = 0.01 ). Comparing two groups with respect to their subtypes of headaches resulted in that the tension-type headache was statistically ( p = 0.008 ) higher in Crohn’s disease group (26/51) than in the control group (12/51). However, no significant difference was found in the migraine-type headache ( p = 1 ). Conclusions . This study indicates that the prevalence of headache is high in patients with Crohn’s disease and most commonly associated with the tension-type headache.
    Full-text · Article · Jan 2016 · Gastroenterology Research and Practice
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    • "Anti-glycan antibodies include anti-mannobioside (AMCA), anti-laminaribioside (ALCA) and anti-chitobioside (ACCA) antibodies directed against glycan epitopes corresponding to Man(a1,3)Man(a), Glc(b1,3)Glc(b) and GlcNAc(b1,4)GlcNAc(b), respectively. In CD patients, the prevalence of these markers is approximately 28% for AMCA, 19–38% for ALCA and 21–40% for ACCA (Li et al., 2008 "
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    ABSTRACT: Abstract The etiology of Crohn's disease (CD), an autoimmune, inflammatory bowel disease (IBD) which affects approximately one million people in Europe, is still unclear. Nevertheless, it is widely accepted that CD could result from an inappropriate inflammatory response to intestinal microorganisms in a genetically susceptible host. Most studies to date have concerned the involvement of bacteria in disease progression. In addition to bacteria, there appears to be a possible link between the commensal yeast Candida albicans and disease development. In this review, in an attempt to link the gut colonization process and the development of CD, we describe the different pathways that are involved in the progression of CD and in the host response to C. albicans, making the yeast a possible initiator of the inflammatory process observed in this IBD.
    Full-text · Article · Jul 2013 · Critical Reviews in Microbiology
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    • "Among several serological markers of CD, the anti-glycan response has been shown to be one of the main features of this disease [4,42]. The origin of this response is still unclear although the possible involvement of C. albicans has been proposed [8] and a link has been shown between Candida colonization and ASCA [43]. "
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    ABSTRACT: Background Crohn’s disease (CD) is associated with elevated anti-glycans antibody response in 60% of CD patients, and 25% of healthy first-degree relatives (HFDRs), suggesting a genetic influence for this humoral response. In mice, anti-glucan antibody response depends on the NLRP3 inflammasome. Here, we explored the effect of mutated CARD8, a component of the inflammasome, on anti-glycans antibody response in human. Methods The association between p.C10X mutation (rs2043211) of the CARD8 gene and the levels of anti-glycans antibody response was examined in 39 CD families. The family-based QTDT association test was used to test for the genetic association between CARD8 p.C10X mutation and anti-glycan antibodies in the pedigrees. The difference in antibody responses determined by ELISA was tested in a subgroup of CD probands (one per family) and in a subgroup of HFDRs using the Wilcoxon Kruskal Wallis non-parametric test. Results The QTDT familial transmission tests showed that the p.C10X mutation of CARD8 was significantly associated with lower levels of antibody to mannans and glucans but not chitin (p=0.024, p=0.0028 and p=0.577, for ASCA, ALCA and ACCA, respectively). These associations were independent of NOD2 and NOD1 genetic backgrounds. The p.C10X mutation significantly associated or displayed a trend toward lower ASCA and ALCA levels (p=0.038 and p=0.08, respectively) only in the subgroup of CD probands. Such associations were not significant for ACCA levels in both subgroups of CD probands and of HFDRs. Conclusion Our results show that ASCA and ALCA but not ACCA levels are under the influence of CARD8 genotype. Alteration of CARD8, a component of inflammasome, is associated with lower levels of antibodies directed to mannans and glucans at least in CD patients.
    Full-text · Article · Mar 2013 · BMC Medical Genetics
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