Antibodies Against Laminaribioside and Chitobioside Are Novel Serologic Markers in Crohn’s Disease

Dotan, Iris; Fishman, Sigal; Dgani, Yaara; Schwartz, Mikael; Karban, Amir; Lerner, Aaron; Weishauss, Oori; Spector, Larissa; Shtevi, Avi; Altstock, Rom T.; Dotan, Nir; Halpern, Zamir

doi:10.1053/j.gastro.2006.04.030

Cited by 217 publications

(220 citation statements)

References 44 publications

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“…These trends are also observed in an independent analysis of the MetaHIT cohort (S11 Fig). research on separate cohorts also found that the community structure of biopsy-associated microbiomes [46][47][48] differed substantially between UC and CD patients, with UC appearing more like controls in the latter two; one study also saw similar trends in functional annotation from shallow shotgun sequencing [46]. UC and CD can also be differentiated serologically, with UC tending to be characterized more by autoantibodies directed at host neutrophils [49] [50], though these may arise through cross-reactivity with microbial proteins like OmpC [51], and CD being characterized more by antibodies against cell-surface glycans [52], Saccharomyces cerevisiae [50], and proteins such as flagellin [53]. This difference in the antigens associated with CD vs. UC may relate in part to biomolecules made and presented by the gut flora.…”

Section: Accurate Metagenome Annotation Clarifies Community Functionamentioning

confidence: 98%

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Nayfach

Bradley

Wyman

et al. 2015

Preprint

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Shotgun metagenomic DNA sequencing is a widely applicable tool for characterizing the functions that are encoded by microbial communities. Several bioinformatic tools can be used to functionally annotate metagenomes, allowing researchers to draw inferences about the functional potential of the community and to identify putative functional biomarkers. However, little is known about how decisions made during annotation affect the reliability of the results. Here, we use statistical simulations to rigorously assess how to optimize annotation accuracy and speed, given parameters of the input data like read length and library size. We identify best practices in metagenome annotation and use them to guide the development of the Shotgun Metagenome Annotation Pipeline (ShotMAP). ShotMAP is an analytically flexible, end-to-end annotation pipeline that can be implemented either on a local computer or a cloud compute cluster. We use ShotMAP to assess how different annotation databases impact the interpretation of how marine metagenome and metatranscriptome functional capacity changes across seasons. We also apply ShotMAP to data obtained from a clinical microbiome investigation of inflammatory bowel disease. This analysis finds that gut microbiota collected from Crohn's disease patients are functionally distinct from gut microbiota collected from either ulcerative colitis patients or healthy controls, with differential abundance of metabolic pathways related to host-microbiome interactions that may serve as putative biomarkers of disease. Author SummaryMicrobial communities perform a wide variety of functions, from marine photosynthesis to aiding digestion in the human gut. Shotgun "metagenomic" sequencing can be used to sample millions of short DNA sequences from such communities directly, without needing to first culture its constituents in the laboratory. Using these data, researchers can survey which functions are encoded by mapping these short sequences to known protein families and pathways. Several tools for this annotation already exist. But, annotation is a multi-step process that includes identification of genes in a metagenome and determination of the type of protein each gene encodes. We currently know little about how different choices of parameters during annotation influences the final results. In this work, we systematically test how several key decisions affect the accuracy and speed of annotation, and based on these results, develop new software for annotation, which we named ShotMAP. We then use ShotMAP to functionally characterize marine communities and gut communities in a clinical cohort of inflammatory bowel disease. We find several functions are differentially represented in the gut microbiome of Crohn's disease patients, which could be candidates for biomarkers and could also offer insight into the pathophysiology of Crohn's. ShotMAP is freely available (https://github.com/sharpton/shotmap).

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Section: Accurate Metagenome Annotation Clarifies Community Functionamentioning

confidence: 98%

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Nayfach

Bradley

Wyman

et al. 2015

Preprint

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“…Antibodies specific to N-glycolylneuraminic acid, a glycan generated by non-human cell lines, are reported to comprise up to 0.1-0.2% of circulating IgG in normal humans (37). Antibodies specific to other glycans have been associated with adult and pediatric Crohn's disease progression (38)(39)(40)(41) (Table I).…”

Section: Nature and Characterization Of Pre-existing Reactivity In Admentioning

confidence: 99%

Pre-existing Antibody: Biotherapeutic Modality-Based Review

Gorovits

Clements-Egan

Birchler

et al. 2016

AAPS J

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Abstract. Pre-existing antibodies to biotherapeutic drugs have been detected in drug-naïve subjects for a variety of biotherapeutic modalities. Pre-existing antibodies are immunoglobulins that are either specific or cross-reacting with a protein or glycan epitopes on a biotherapeutic compound. Although the exact cause for pre-existing antibodies is often unknown, environmental exposures to non-human proteins, glycans, and structurally similar products are frequently proposed as factors. Clinical consequences of the pre-existing antibodies vary from an adverse effect on patient safety to no impact at all and remain highly dependent on the biotherapeutic drug modality and therapeutic indication. As such, pre-existing antibodies are viewed as an immunogenicity risk factor requiring a careful evaluation. Herein, the relationships between biotherapeutic modalities to the nature, prevalence, and clinical consequences of pre-existing antibodies are reviewed. Initial evidence for pre-existing antibody is often identified during anti-drug antibody (ADA) assay development. Other interfering factors known to cause false ADA positive signal, including circulating multimeric drug target, rheumatoid factors, and heterophilic antibodies, are discussed.

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“…Comme pour les anticorps anti-mannane on observe leur disparition quasitotale au moment de la dissémination sanguine de la levure, ce qui suggère la formation de complexes in vivo avec des antigènes homologues relargués par C. albicans ou une sidération transitoire de la réponse anticorps. , sont utilisés en complément des ASCA dans le diagnostic sérologique de la MC (Figure 1) [35]. Il était dès lors logique d'explorer, si, au même titre que les ASCA, la synthèse des ALCA et les ACCA pouvait être induite lors d'une infection par C. albicans.…”

Section: éTablissement De Relations Sérologiques Présence D'asca Chezunclassified

Glycannes pariétaux de levures et anticorps spécifiques

et al. 2009

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Une des spécificités « historiques » de la mycologie médi-cale est d'utiliser les anticorps expérimentaux et humains produits contre les molécules fongiques afin de mieux comprendre la biologie des champignons et les processus pathologiques qu'ils induisent, et d'en faciliter le diagnostic [4][5][6]. Chez les champignons, les « glycannes » 1 représentent jusqu'à 80 % de la paroi [1-3] et il n'est donc pas étonnant que pour les espèces impliquées en pathologie humaine, ils soient la cible privilégiée de la réponse immune. Nous proposons dans cette revue une synthèse des données expérimentales et cliniques démontrant tout l'intérêt des anticorps anti-glycannes pour l'exploration des mécanismes physiopathologiques et pour le diagnostic, et nous l'illustrerons dans deux entités cliniques distinctes, les candidoses et la maladie de Crohn.1 Les glycannes comprennent les polysaccharides, les oligosaccharides et les parties saccharidiques des glycoconjugués (où ils sont associés à des protéines ou à des lipides). C. albicans, candidoses et maladie de CrohnCandida et Candidoses C. albicans est un hôte naturel du tube digestif et du vagin humain. Si on ne connaît pas le bénéfice de ce portage, on en connaît en revanche les effets néfastes : les candidoses vaginales affectent 75 % des femmes au moins une fois dans leur existence et les candidoses oro-pharyngées 90 % des patients infectés par le VIH (virus de l'immunodéficience humaine) parvenus au stade SIDA. Ces chiffres attestent l'omniprésence de C. albicans sur les muqueuses humaines. Cette colonisation est également à l'origine d'infections profondes survenant en milieu hospitalier chez des patients affaiblis par leur pathologie primaire et les actes médico-chirurgicaux mis en oeuvre pour la traiter [7]. L'importance et la gravité des candidoses nosocomiales ont été sous estimées jusqu'à ce que les grandes études épi-démiologiques réalisées dans les années 1990 révèlent

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Antibodies Against Laminaribioside and Chitobioside Are Novel Serologic Markers in Crohn’s Disease

Cited by 217 publications

References 44 publications

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Automated and accurate estimation of gene family abundance from shotgun metagenomes

Pre-existing Antibody: Biotherapeutic Modality-Based Review

Glycannes pariétaux de levures et anticorps spécifiques

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