期刊
GASTROENTEROLOGY
卷 154, 期 5, 页码 1320-+出版社
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1053/j.gastro.2018.01.002
关键词
IBD; Glycans; Glycopeptides; Biomarker
资金
- European Union Seventh Framework Programmes Inflammatory Bowel Disease Biomarkers [305479]
- H grants SYSCID [733100]
- GlySign [722095]
- IMForFuture [721815]
- European Structural and Investment Funds IRI [KK.01.2.1.01.0003]
- Croatian National Centre of Research Excellence in Personalized Healthcare [KK.01.1.1.01.0010]
- Netherlands Genomic Initiative Horizon Programme Zenith project [93511033]
- National Institutes of Health [U01DK062413, P01DK046763, R01HS021747, U01AI067068]
- MRC [G0600237, MC_PC_U127527198, MC_UU_00007/1, G0701898, MC_U127527198, G0600329] Funding Source: UKRI
- AGENCY FOR HEALTHCARE RESEARCH AND QUALITY [R01HS021747] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI067068] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R56DK095820, P01DK046763, U01DK062413] Funding Source: NIH RePORTER
- Cancer Research UK [12076, 18927] Funding Source: researchfish
- Medical Research Council [MC_U127527198, MC_UU_00007/1, G0600237, G0701898, MC_PC_U127527198, G0600329] Funding Source: researchfish
- Worldwide Cancer Research [12-1087] Funding Source: researchfish
- Crohn"
- s and Colitis UK [M16-1] Funding Source: researchfish
BACKGROUND AND AIMS: Causes of inflammatory bowel diseases are not well understood and the most prominent forms, Crohn's disease (CD) and ulcerative colitis (UC), are sometimes hard to distinguish. Glycosylation of IgG has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. We evaluated changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups. METHODS: We analyzed 3441 plasma samples obtained from 2 independent cohorts of patients with CD (874 patients from Italy and 391 from the United States) or UC (1056 from Italy and 253 from the US and healthy individuals [controls]; 427 in Italy and 440 from the United States). IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry. We analyzed associations between disease status (UC vs controls, CD vs controls, and UC vs CD) and glycopeptide traits, and associations between clinical characteristics and glycopeptide traits, using a logistic regression model with age and sex included as covariates. RESULTS: Patients with CD or UC had lower levels of IgG galactosylation than controls. For example, the odds ratio (OR) for IgG1 galactosylation in patients with CD was 0.59 (95% confidence interval [CI], 0.51-0.69) and for patients with UC was 0.81 (95% CI, 0.71-0.92). Fucosylation of IgG was increased in patients with CD vs controls (for IgG1: OR, 1.27; 95% CI, 1.121.44), but decreased in patients with UC vs controls (for IgG23: OR, 0.72; 95% CI, 0.63-0.82). Decreased galactosylation associated with more severe CD or UC, including the need for surgery in patients with UC vs controls (for IgG1: OR, 0.69; 95% CI, 0.54-0.89) and in patients with CD vs controls (for IgG23: OR, 0.78; 95% CI, 0.66-0.91). CONCLUSIONS: In a retrospective analysis of plasma samples from patients with CD or UC, we associated levels of IgG Fc-glycosylation with disease (compared to controls) and its clinical features. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.
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