Manuscript Doi : 10.1093/ecco-jcc/jjv063

Journal of Crohn's and Colitis Advance Access published April 19, 2015

Association of anti-Glycan antibodies and Inflammatory Bowel Disease Course Short title: Anti-Glycan as new surrogate markers of IBD S Paul, PhD1*, G Boschetti, MD2*, M. Rinaudo-Gaujous, MD1, A Moreau, PharmD1, E Del Tedesco, MD3, J. Bonneau, MD1, E. Presles, PhD4, F Mounsef, PhD5, L Clavel, MD3,C

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Genin, MD-PhD1, B Flourié, MD, PhD2 , J-M Phelip, MD, PhD3, S Nancey, MD, PhD2 and X Roblin, MD, PhD3 1

Laboratory of Immunology, University Hospital & GIMAP EA3064 / CIC INSERM 1408

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Université de Lyon, Saint-Etienne, France. 2Department of Gastroenterology, Hospices Civils de Lyon, Lyon-Sud Hospital, Pierre-Benite, France & INSERM U1111, International Center for Research in Infectiology (CIRI), Lyon, France.

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Department of Gastroenterology,

University Hospital, Saint-Etienne, France. 4DRCI-CIC, University Hospital, Saint-Etienne,

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France. 5 Pharmacy, University Hospital, Saint-Etienne, France

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*Coprimary first authors, Equal contribution

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Word count: 5115

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Correspondence to: Xavier Roblin, MD, PhD Department of Gastroenterology Saint-Etienne University Hospital 42 Saint-Etienne, France [email protected]

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Authorship Statement: Guarantor of the article: Stéphane PAUL Specific author contributions: GB, JB, MR, AM, EDT, EP, FM, LC, CG, BF, JMP, SN have performed the research, SN, GB, JB, XR and SP collected and analysed the data, GB and SP designed the research study and wrote the paper. All authors approved the final version of the manuscript.

Abbreviations: Crohn’s disease (CD); Ulcerative colitis (UC); Inflammatory bowel disease (IBD); perinuclear antineutrophil cytoplasmic antibody (pANCA); mannobioside IgG antibodies (AMCA), anti-chitobioside IgA (ACCA), anti-laminaribioside IgG antibodies (ALCA), anti-laminarin (anti-L), anti-chitine (anti-C); Tumor necrosis factor (TNFα); AntiTumor Necrosis Factor (anti-TNF); Positive Predictive Value: PPV; Negative Predictive Value: NPV; Sensibility: Ss; Specificity: Sp.

1 Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: [email protected]

ABSTRACT BACKGROUND & AIMS: The usefulness of anti-glycan antibodies alone or combined with ASCA or pANCA antibodies for diagnosis of inflammatory bowel disease (IBD), differentiation between Crohn’s disease (CD) and ulcerative colitis (UC), disease stratification including IBD phenotype and also for determination of the course of the disease, remain

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unclear.

METHODS: A large panel of serological anti-glycan carbohydrate antibodies, including antimannobioside IgG antibodies (AMCA), anti-chitobioside IgA (ACCA), anti-laminaribioside

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IgG antibodies (ALCA), anti-laminarin (anti-L) and anti-chitine (anti-C) were measured in the serum from a cohort of 195 patients with inflammatory bowel disease (IBD) (107 CD and 88 UC) and the respective accuracy of isolated or combined markers for diagnosis, disease differentiation, and stratification disease phenotype severity of the disease course defined by a

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wide panel of criteria obtained from the past medical history was assessed.

RESULTS: The positivity of at least one anti-glycan antibody was detected in a significant higher proportion of CD and UC compared with healthy controls (p 0.0001 and p 0.0007,

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respectively). Whereas ASCA and ANCA antibody status had the highest efficacy to be associated with CD from UC (AUROC=0.70 for each), the adjunction of anti-laminarin

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antibody substantially improved the differentiation between CD and UC (AUROC=0.77). Titers of ACCA ( 51 U/ml) and anti-laminarin ( 31 U/ml) were significantly linked with a higher association with steroid-dependency (OR=2.0 1.0-4.0 , p=0.03 and OR=2.4 1.1-5.2 ,

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p=0.02, respectively). We further defined the respective performance of anti-glycan antibodies to discriminate between patients with severe or not severe CD and UC course and

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determined the associated optimal cut-off values: severe CD course was significantly more likely in case of AMCA > 77 U/mL (OR=4.3; p=0.002), ASCA > 63 U/mL (OR=3.5; p 50 U/mL (OR=2.8; p 52 U/mL (OR=3.4; p=0.04); ACCA > 25 U/mL (OR=3.0; p

Association of Anti-glycan Antibodies and Inflammatory Bowel Disease Course.

The usefulness of anti-glycan antibodies alone or combined with anti-Saccharomyces cerevisiae [ASCA] or perinuclear antineutrophil cytoplasmic [pANCA]...
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