46 results on '"IBD-BIOM Consortium"'
Search Results
2. Immunoglobulin A Glycosylation Differs between Crohn’s Disease and Ulcerative Colitis
- Author
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Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, IBD-BIOM Consortium, Afd Biomol.Mass Spect. and Proteomics, Biomolecular Mass Spectrometry and Proteomics, and IBD-BIOM Consortium
- Published
- 2023
3. Immunoglobulin A Glycosylation Differs between Crohn's Disease and Ulcerative Colitis.
- Author
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Clerc F, Reiding KR, de Haan N, Koeleman CAM, Hipgrave Ederveen AL, Manetti N, Dotz V, Annese V, and Wuhrer M
- Subjects
- Humans, Glycosylation, Immunoglobulin A, Biomarkers, Crohn Disease diagnosis, Crohn Disease epidemiology, Colitis, Ulcerative diagnosis, Colitis, Ulcerative epidemiology, Inflammatory Bowel Diseases
- Abstract
Inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC), are chronic and relapsing inflammations of the digestive tract with increasing prevalence, yet they have unknown origins or cure. CD and UC have similar symptoms but respond differently to surgery and medication. Current diagnostic tools often involve invasive procedures, while laboratory markers for patient stratification are lacking. Large glycomic studies of immunoglobulin G and total plasma glycosylation have shown biomarker potential in IBD and could help determine disease mechanisms and therapeutic treatment choice. Hitherto, the glycosylation signatures of plasma immunoglobulin A, an important immunoglobulin secreted into the intestinal mucin, have remained undetermined in the context of IBD. Our study investigated the associations of immunoglobulin A1 and A2 glycosylation with IBD in 442 IBD cases (188 CD and 254 UC) and 120 healthy controls by reversed-phase liquid chromatography electrospray-ionization mass spectrometry of tryptic glycopeptides. Differences of IgA O- and N -glycosylation (including galactosylation, bisection, sialylation, and antennarity) between patient groups were associated with the diseases, and these findings led to the construction of a statistical model to predict the disease group of the patients without the need of invasive procedures. This study expands the current knowledge about CD and UC and could help in the development of noninvasive biomarkers and better patient care.
- Published
- 2023
- Full Text
- View/download PDF
4. Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease.
- Author
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Shubhakar A, Jansen BC, Adams AT, Reiding KR, Ventham NT, Kalla R, Bergemalm D, Urbanowicz PA, Gardner RA, Wuhrer M, Halfvarson J, Satsangi J, Fernandes DL, and Spencer DIR
- Subjects
- Humans, Glycomics, Biomarkers, Polysaccharides, Colitis, Ulcerative diagnosis, Crohn Disease complications, Inflammatory Bowel Diseases complications
- Abstract
Biomarkers to guide clinical decision making at diagnosis of inflammatory bowel disease [IBD] are urgently needed. We investigated a composite serum N-glycomic biomarker to predict future disease course in a discovery cohort of 244 newly diagnosed IBD patients. In all, 47 individual glycan peaks were analysed using ultra-high performance liquid chromatography, identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio [HR] 25.9, p = 1.1 × 10-12; 95% confidence interval [CI], 8.52-78.78). Application to an independent replication cohort of 54 IBD patients yielded an HR of 5.1 [p = 1.1 × 10-5; 95% CI, 2.54-10.1]. These data demonstrate the prognostic capacity of serum N-glycan biomarkers and represent a step towards personalised medicine in IBD., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2023
- Full Text
- View/download PDF
5. Serum N-Glycomic Biomarkers Predict Treatment Escalation in Inflammatory Bowel Disease
- Author
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Archana Shubhakar, Bas C Jansen, Alex T. Adams, Karli R. Reiding, Nicholas T. Ventham, Rahul Kalla, Daniel Bergemalm, Paulina A Urbanowicz, Richard A Gardner, IBD-BIOM Consortium, Jonas Halfvarson, Jack Satsangi, Daryl L Fernandes, Manfred Wuhrer, and Daniel I R Spencer
- Abstract
A blood-based prognostic biomarker to guide clinical decision-making at diagnosis of inflammatory bowel disease (IBD) would be immensely helpful. We investigated a composite serum N-glycomic biomarker to predict future disease course in 244 newly diagnosed IBD patients. Forty-seven individual glycan peaks were analysed using ultra-high performance liquid chromatography identifying 105 glycoforms from which 24 derived glycan traits were calculated. Multivariable logistic regression was performed to determine associations of derived glycan traits with disease. Cox proportional hazard models were used to predict treatment escalation from first-line treatment to biologics or surgery (hazard ratio (HR) 25.9, p = 1.1×10− 12; 95% confidence interval (CI), 8.52–78.78). Application to an independent replication cohort of 54 IBD patients yielded a HR of 5.1 (p = 1.1×10− 5; 95% CI, 2.54–10.1). These data demonstrate the predictive capacity of serum N-glycan biomarkers and represent a step towards personalized medicine in IBD.
- Published
- 2021
6. Correction: changes to serum sample tube and processing methodology does not cause inter-individual variation in automated whole serum N-glycan profiling in health and disease.
- Author
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Nicholas T Ventham, Richard A Gardner, Nicholas A Kennedy, Archana Shubhakar, Rahul Kalla, Elaine R Nimmo, IBD-BIOM Consortium, Daryl L Fernandes, Jack Satsangi, and Daniel I R Spencer
- Subjects
Medicine ,Science - Published
- 2015
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- View/download PDF
7. Changes to serum sample tube and processing methodology does not cause Intra-Individual [corrected] variation in automated whole serum N-glycan profiling in health and disease.
- Author
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Nicholas T Ventham, Richard A Gardner, Nicholas A Kennedy, Archana Shubhakar, Rahul Kalla, Elaine R Nimmo, IBD-BIOM Consortium, Daryl L Fernandes, Jack Satsangi, and Daniel I R Spencer
- Subjects
Medicine ,Science - Abstract
Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system.25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual.There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status.The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures.
- Published
- 2015
- Full Text
- View/download PDF
8. Genome-Wide Methylation Profiling in 229 Patients With Crohn's Disease Requiring Intestinal Resection: Epigenetic Analysis of the Trial of Prevention of Post-operative Crohn's Disease (TOPPIC).
- Author
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Ventham NT, Kennedy NA, Kalla R, Adams AT, Noble A, Ennis H, Mowat C, Dunlop MG, and Satsangi J
- Subjects
- Adult, Humans, Child, Child, Preschool, DNA Methylation genetics, Genome-Wide Association Study methods, Epigenesis, Genetic, Membrane Proteins genetics, Crohn Disease genetics, Crohn Disease surgery, Inflammatory Bowel Diseases genetics
- Abstract
Background & Aims: DNA methylation alterations may provide important insights into gene-environment interaction in cancer, aging, and complex diseases, such as inflammatory bowel disease (IBD). We aim first to determine whether the circulating DNA methylome in patients requiring surgery may predict Crohn's disease (CD) recurrence following intestinal resection; and second to compare the circulating methylome seen in patients with established CD with that we had reported in a series of inception cohorts., Methods: TOPPIC was a placebo-controlled, randomized controlled trial of 6-mercaptopurine at 29 UK centers in patients with CD undergoing ileocolic resection between 2008 and 2012. Genomic DNA was extracted from whole blood samples from 229 of the 240 patients taken before intestinal surgery and analyzed using 450KHumanMethylation and Infinium Omni Express Exome arrays (Illumina, San Diego, CA). Coprimary objectives were to determine whether methylation alterations may predict clinical disease recurrence; and to assess whether the epigenetic alterations previously reported in newly diagnosed IBD were present in the patients with CD recruited into the TOPPIC study. Differential methylation and variance analysis was performed comparing patients with and without clinical evidence of recurrence. Secondary analyses included investigation of methylation associations with smoking, genotype (MeQTLs), and chronologic age. Validation of our previously published case-control observation of the methylome was performed using historical control data (CD, n = 123; Control, n = 198)., Results: CD recurrence in patients following surgery is associated with 5 differentially methylated positions (Holm P < .05), including probes mapping to WHSC1 (P = 4.1 × 10
-9 , Holm P = .002) and EFNA3 (P = 4.9 × 10-8 , Holm P = .02). Five differentially variable positions are demonstrated in the group of patients with evidence of disease recurrence including a probe mapping to MAD1L1 (P = 6.4 × 10-5 ). DNA methylation clock analyses demonstrated significant age acceleration in CD compared with control subjects (GrimAge + 2 years; 95% confidence interval, 1.2-2.7 years), with some evidence for accelerated aging in patients with CD with disease recurrence following surgery (GrimAge +1.04 years; 95% confidence interval, -0.04 to 2.22). Significant methylation differences between CD cases and control subjects were seen by comparing this cohort in conjunction with previously published control data, including validation of our previously described differentially methylated positions (RPS6KA2 P = 1.2 × 10-19 , SBNO2 = 1.2 × 10-11 ) and regions (TXK [false discovery rate, P = 3.6 × 10-14 ], WRAP73 [false discovery rate, P = 1.9 × 10-9 ], VMP1 [false discovery rate, P = 1.7 × 10-7 ], and ITGB2 [false discovery rate, P = 1.4 × 10-7 ])., Conclusions: We demonstrate differential methylation and differentially variable methylation in patients developing clinical recurrence within 3 years of surgery. Moreover, we report replication of the CD-associated methylome, previously characterized only in adult and pediatric inception cohorts, in patients with medically refractory disease needing surgery., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
9. Changes to Serum Sample Tube and Processing Methodology Does Not Cause Inter-Individual Variation in Automated Whole Serum N-Glycan Profiling in Health and Disease
- Author
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Nicholas T Ventham, Richard A Gardner, Nicholas A Kennedy, Archana Shubhakar, Rahul Kalla, Elaine R Nimmo, IBD-BIOM Consortium, Daryl L Fernandes, Jack Satsangi, and Daniel I R Spencer
- Subjects
Adult ,Male ,Blood Specimen Collection ,Multidisciplinary ,lcsh:R ,Correction ,lcsh:Medicine ,Blood Proteins ,Middle Aged ,Inflammatory Bowel Diseases ,Polysaccharides ,Humans ,Female ,lcsh:Q ,lcsh:Science ,Biomarkers ,Blood Chemical Analysis ,Chromatography, High Pressure Liquid ,Glycoproteins - Abstract
Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system.25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual.There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status.The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures.
- Published
- 2015
10. Plasma N-Glycan Signatures Are Associated With Features of Inflammatory Bowel Diseases.
- Author
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Clerc F, Novokmet M, Dotz V, Reiding KR, de Haan N, Kammeijer GSM, Dalebout H, Bladergroen MR, Vukovic F, Rapp E, Targan SR, Barron G, Manetti N, Latiano A, McGovern DPB, Annese V, Lauc G, and Wuhrer M
- Subjects
- Adult, Biomarkers blood, Case-Control Studies, Colitis, Ulcerative diagnosis, Crohn Disease diagnosis, Disease Progression, Female, Glycosylation, Humans, Logistic Models, Male, Middle Aged, Protein Processing, Post-Translational, Colitis, Ulcerative blood, Crohn Disease blood, Polysaccharides blood
- Abstract
Background & Aims: Biomarkers are needed for early detection of Crohn's disease (CD) and ulcerative colitis (UC) or to predict patient outcomes. Glycosylation is a common and complex posttranslational modification of proteins that affects their structure and activity. We compared plasma N-glycosylation profiles between patients with CD or UC and healthy individuals (controls)., Methods: We analyzed the total plasma N-glycomes of 2635 patients with inflammatory bowel diseases and 996 controls by mass spectrometry with a linkage-specific sialic acid derivatization technique. Plasma samples were acquired from 2 hospitals in Italy (discovery cohort, 1989 patients with inflammatory bowel disease [IBD] and 570 controls) and 1 medical center in the United States (validation cohort, 646 cases of IBD and 426 controls). Sixty-three glycoforms met our criteria for relative quantification and were extracted from the raw data with the software MassyTools. Common features shared by the glycan compositions were combined in 78 derived traits, including the number of antennae of complex-type glycans and levels of fucosylation, bisection, galactosylation, and sialylation. Associations of plasma N-glycomes with age, sex, CD, UC, and IBD-related parameters such as disease location, surgery and medication, level of C-reactive protein, and sedimentation rate were tested by linear and logistic regression., Results: Plasma samples from patients with IBD had a higher abundance of large-size glycans compared with controls, a decreased relative abundance of hybrid and high-mannose structures, lower fucosylation, lower galactosylation, and higher sialylation (α2,3- and α2,6-linked). We could discriminate plasma from patients with CD from that of patients with UC based on higher bisection, lower galactosylation, and higher sialylation (α2,3-linked). Glycosylation patterns were associated with disease location and progression, the need for a more potent medication, and surgery. These results were replicated in a large independent cohort., Conclusions: We performed high-throughput analysis to compare total plasma N-glycomes of individuals with vs without IBD and to identify patterns associated with disease features and the need for treatment. These profiles might be used in diagnosis and for predicting patients' responses to treatment., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
- Full Text
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11. Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
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Ventham NT, Kennedy NA, Adams AT, Kalla R, Heath S, O'Leary KR, Drummond H, Wilson DC, Gut IG, Nimmo ER, and Satsangi J
- Subjects
- Adult, Case-Control Studies, Cohort Studies, Colitis, Ulcerative blood, Crohn Disease blood, Epigenesis, Genetic, Epigenomics methods, Female, Gene Expression Profiling methods, Gene-Environment Interaction, Genotype, Humans, Linkage Disequilibrium, Male, Membrane Proteins genetics, MicroRNAs genetics, Middle Aged, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Protein-Tyrosine Kinases genetics, Colitis, Ulcerative genetics, Crohn Disease genetics, DNA Methylation genetics, Genetic Predisposition to Disease, Quantitative Trait Loci genetics
- Abstract
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8
+ T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression., Competing Interests: N.T.V., Lecture fee(s): MSD, Ferring, N.A.V. Conflict with: speaker fees MSD, Takeda, Falk, Pharmacosmos, Allergan. Shire Travel bursary, D.C.W. Conflict with: Consultant for: Pfizer, Conflict with: MSD investigator grant, MSD speaker fee, and Ferring speaker fee, J.S. Conflict with: Consultant for: Takeda, Conflict with: MSD speaker fees. Shire travelling expenses. The remaining authors declare no competing financial interests.- Published
- 2016
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12. Correction: changes to serum sample tube and processing methodology does not cause inter-individual variation in automated whole serum N-glycan profiling in health and disease.
- Author
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Ventham NT, Gardner RA, Kennedy NA, Shubhakar A, Kalla R, Nimmo ER, Fernandes DL, Satsangi J, and Spencer DI
- Published
- 2015
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13. Inflammatory bowel disease associates with proinflammatory potential of the immunoglobulin G glycome.
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Trbojević Akmačić I, Ventham NT, Theodoratou E, Vučković F, Kennedy NA, Krištić J, Nimmo ER, Kalla R, Drummond H, Štambuk J, Dunlop MG, Novokmet M, Aulchenko Y, Gornik O, Campbell H, Pučić Baković M, Satsangi J, and Lauc G
- Subjects
- Adult, Case-Control Studies, Chromatography, Liquid, Female, Glycosylation, Humans, Immunoglobulin G blood, Immunoglobulin G genetics, Inflammatory Bowel Diseases blood, Inflammatory Bowel Diseases genetics, Logistic Models, Male, Middle Aged, Phenotype, Polysaccharides genetics, Polysaccharides metabolism, ROC Curve, Immunoglobulin G immunology, Inflammatory Bowel Diseases immunology, Polysaccharides immunology
- Abstract
Background: Glycobiology is an underexplored research area in inflammatory bowel disease (IBD), and glycans are relevant to many etiological mechanisms described in IBD. Alterations in N-glycans attached to the immunoglobulin G (IgG) Fc fragment can affect molecular structure and immunological function. Recent genome-wide association studies reveal pleiotropy between IBD and IgG glycosylation. This study aims to explore IgG glycan changes in ulcerative colitis (UC) and Crohn's disease (CD)., Methods: IgG glycome composition in patients with UC (n = 507), CD (n = 287), and controls (n = 320) was analyzed by ultra performance liquid chromatography., Results: Statistically significant differences in IgG glycome composition between patients with UC or CD, compared with controls, were observed. Both UC and CD were associated with significantly decreased IgG galactosylation (digalactosylation, UC: odds ratio [OR] = 0.71; 95% confidence interval [CI], 0.5-0.9; P = 0.01; CD: OR = 0.41; CI, 0.3-0.6; P = 1.4 × 10) and significant decrease in the proportion of sialylated structures in CD (OR = 0.46, CI, 0.3-0.6, P = 8.4 × 10). Logistic regression models incorporating measured IgG glycan traits were able to distinguish UC and CD from controls (UC: P = 2.13 × 10 and CD: P = 2.20 × 10), with receiver-operator characteristic curves demonstrating better performance of the CD model (area under curve [AUC] = 0.77) over the UC model (AUC = 0.72) (P = 0.026). The ratio of the presence to absence of bisecting GlcNAc in monogalactosylated structures was increased in patients with UC undergoing colectomy compared with no colectomy (FDR-adjusted, P = 0.05)., Conclusions: The observed differences indicate significantly increased inflammatory potential of IgG in IBD. Changes in IgG glycosylation may contribute to IBD pathogenesis and could alter monoclonal antibody therapeutic efficacy. IgG glycan profiles have translational potential as IBD biomarkers.
- Published
- 2015
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14. Changes to serum sample tube and processing methodology does not cause Intra-Individual [corrected] variation in automated whole serum N-glycan profiling in health and disease.
- Author
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Ventham NT, Gardner RA, Kennedy NA, Shubhakar A, Kalla R, Nimmo ER, Fernandes DL, Satsangi J, and Spencer DI
- Subjects
- Adult, Biomarkers blood, Blood Chemical Analysis, Blood Proteins isolation & purification, Blood Proteins metabolism, Chromatography, High Pressure Liquid, Female, Glycoproteins isolation & purification, Humans, Inflammatory Bowel Diseases blood, Male, Middle Aged, Polysaccharides isolation & purification, Blood Specimen Collection instrumentation, Glycoproteins blood, Polysaccharides blood
- Abstract
Introduction: Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system., Methods: 25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual., Results: There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status., Conclusions: The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures.
- Published
- 2015
- Full Text
- View/download PDF
15. Challenges in IBD Research 2024: Precision Medicine.
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Syed, Sana, Boland, Brigid S, Bourke, Lauren T, Chen, Lea Ann, Churchill, Laurie, Dobes, Angela, Greene, Adam, Heller, Caren, Jayson, Christina, Kostiuk, Benjamin, Moss, Alan, Najdawi, Fedaa, Plung, Lori, Rioux, John D, Rosen, Michael J, Torres, Joana, Zulqarnain, Fatima, and Satsangi, Jack
- Published
- 2024
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16. Inflammatory bowel disease associates with pro-inflammatory potential of the IgG glycome
- Author
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Akmacic, Irena Trbojevic, Ventham, Nicholas T., Theodoratou, Evropi, Vuckovic, Frano, Kennedy, Nicholas A., Kristic, Jasminka, Nimmo, Elaine, Kalla, Rahul, Drummond, Hazel E., Stambuk, Jerko, Malcolm Dunlop, Novokmet, Mislav, Aulchenko, Yurii, Gornik, Olga, Campbell, Harry, Pucic-Bakovic, Maja, Satsangi, Jack, Lauc, Gordan, and Ibd Biom, Consortium
17. Soluble markers of viral rebound and post-treatment HIV control.
- Author
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Giron LB, Pasternak AO, and Abdel-Mohsen M
- Abstract
Purpose of Review: We focus on the different classes of biological molecules measurable in easily accessible bodily fluids that have the potential to serve as biomarkers for the HIV post-treatment controller (PTC) phenotype and/or the timing of viral rebound after stopping antiretroviral therapy (ART)., Recent Findings: Various viral components and host factors measurable in body fluids can play crucial roles in understanding and predicting the PTC phenotype. We review recent findings linking viral components, the quantitative and qualitative features of antibodies (including autologous HIV-specific antibodies), markers of inflammation and tissue damage, other host proteins (including hormones such as sex hormones), as well as metabolites, extracellular vesicles, and cell-free DNA to HIV control post-ART interruption. Several of these molecules can or have the potential to predict the time and probability of viral rebound after stopping ART and are biologically active molecules that can directly or indirectly (by modulating immune pressures) impact the size and activity of HIV reservoirs during and post-ART interruption., Summary: A comprehensive model combining multiple markers is needed to predict the PTC phenotype. This model can be leveraged to predict and understand the PTC phenotype, which can guide novel curative interventions to replicate this phenotype in post-treatment non-controllers., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2024
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18. Inflammatory Bowel Diseases: An Updated Overview on the Heat Shock Protein Involvement.
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Federica, Scalia, Francesco, Carini, Sabrina, David, Marco, Giammanco, Margherita, Mazzola, Francesca, Rappa, Noemi Irma, Bressan, Giorgio, Maida, and Giovanni, Tomasello
- Subjects
INFLAMMATORY bowel diseases ,HEAT shock proteins ,CROHN'S disease ,ULCERATIVE colitis ,GUT microbiome ,MOLECULAR chaperones - Abstract
Inflammatory bowel diseases (IBDs) represent chronic idiopathic disorders, including Crohn's disease (CD) and ulcerative colitis (UC), in which one of the trigger factors is represented by aberrant immune interactions between the intestinal epithelium and the intestinal microbiota. The involvement of heat shock proteins (HSPs) as etiological and pathogenetic factors is becoming of increasing interest. HSPs were found to be differentially expressed in the intestinal tissues and sera of patients with CD and UC. It has been shown that HSPs can play a dual role in the disease, depending on the stage of progression. They can support the inflammatory and fibrosis process, but they can also act as protective factors during disease progression or before the onset of one of the worst complications of IBD, colorectal cancer. Furthermore, HSPs are able to mediate the interaction between the intestinal microbiota and intestinal epithelial cells. In this work, we discuss the involvement of HSPs in IBD considering their genetic, epigenetic, immune and molecular roles, referring to the most recent works present in the literature. With our review, we want to shed light on the importance of further exploring the role of HSPs, or even better, the role of the molecular chaperone system (CS), in IBD: various molecules of the CS including HSPs may have diagnostic, prognostic and therapeutic potential, promoting the creation of new drugs that could overcome the side-effects of the therapies currently used. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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19. Microbial–Immune Crosstalk in Elderly-Onset Inflammatory Bowel Disease: Unchartered Territory.
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Meng, Guanmin, Monaghan, Tanya M, Duggal, Niharika A, Tighe, Paddy, and Peerani, Farhad
- Published
- 2023
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20. Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2017–2018.
- Author
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Harvey, David J.
- Subjects
MASS spectrometry ,GLYCOCONJUGATES ,CARBOHYDRATES ,GLYCOLIPIDS ,GLYCOPROTEIN analysis ,ION mobility ,DESORPTION - Abstract
This review is the tenth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2018. Also included are papers that describe methods appropriate to glycan and glycoprotein analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, new methods, matrices, derivatization, MALDI imaging, fragmentation and the use of arrays. The second part of the review is devoted to applications to various structural types such as oligo‐ and poly‐saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Most of the applications are presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and highlights the impact that MALDI imaging is having across a range of diciplines. MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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21. Genetic and Epigenetic Etiology of Inflammatory Bowel Disease: An Update.
- Author
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Jarmakiewicz-Czaja, Sara, Zielińska, Magdalena, Sokal, Aneta, and Filip, Rafał
- Subjects
INFLAMMATORY bowel diseases ,DISEASE remission ,DISEASE exacerbation ,ETIOLOGY of diseases ,CROHN'S disease ,EPIGENETICS - Abstract
Inflammatory bowel disease (IBD) is a chronic disease with periods of exacerbation and remission of the disease. The etiology of IBD is not fully understood. Many studies point to the presence of genetic, immunological, environmental, and microbiological factors and the interactions between them in the occurrence of IBD. The review looks at genetic factors in the context of both IBD predisposition and pharmacogenetics. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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22. OC-010 Epigenome-wide dna methylation profiling in inflammatory bowel disease
- Author
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Ventham, NT, Kennedy, NA, Adams, AT, Kalla, R, O’Leary, KR, Wilson, DC, Nimmo, ER, and Satsangi, J
- Published
- 2015
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23. Early Diagnosis, Early Stratification, and Early Intervention to Deliver Precision Medicine in IBD.
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Noor, Nurulamin M, Sousa, Paula, Paul, Stéphane, and Roblin, Xavier
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- 2022
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24. Effects of DNA methylation and its application in inflammatory bowel disease (Review).
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Akanyibah, Francis Atim, Zhu, Yi, Wan, Aijun, Ocansey, Dickson Kofi Wiredu, Xia, Yuxuan, Fang, An-Ning, and Mao, Fei
- Published
- 2024
- Full Text
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25. Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD—What, Why, and How.
- Author
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Fiocchi, Claudio, Dragoni, Gabriele, Iliopoulos, Dimitrios, Katsanos, Konstantinos, Ramirez, Vicent Hernandez, Suzuki, Kohei, and Committee, Scientific Workshop Steering
- Published
- 2021
- Full Text
- View/download PDF
26. ANALYSIS OF CARBOHYDRATES AND GLYCOCONJUGATES BY MATRIX‐ASSISTED LASER DESORPTION/IONIZATION MASS SPECTROMETRY: AN UPDATE FOR 2015–2016.
- Author
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Harvey, David J.
- Subjects
MATRIX-assisted laser desorption-ionization ,MASS spectrometry ,CARBOHYDRATES ,GLYCOLIPIDS ,GLYCOCONJUGATES ,CHEMICAL reactions ,ION mobility ,DESORPTION - Abstract
This review is the ninth update of the original article published in 1999 on the application of matrix‐assisted laser desorption/ionization (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2016. Also included are papers that describe methods appropriate to analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, fragmentation and arrays. The second part of the review is devoted to applications to various structural types such as oligo‐ and poly‐saccharides, glycoproteins, glycolipids, glycosides and biopharmaceuticals. Much of this material is presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and the enormous impact that MALDI imaging is having. MALDI, although invented over 30 years ago is still an ideal technique for carbohydrate analysis and advancements in the technique and range of applications show no sign of deminishing. © 2020 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
27. Serum proteomic profiling at diagnosis predicts clinical course, and need for intensification of treatment in inflammatory bowel disease.
- Author
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Kalla, R, Adams, A T, Bergemalm, D, Vatn, S, Kennedy, N A, Ricanek, P, Lindstrom, J, Ocklind, A, Hjelm, F, Ventham, N T, Ho, G T, Petren, C, Repsilber, D, Söderholm, J, Pierik, M, D'Amato, M, Gomollón, F, Olbjorn, C, Jahnsen, J, and Vatn, M H
- Published
- 2021
- Full Text
- View/download PDF
28. Whole Blood Profiling of T-cell-Derived microRNA Allows the Development of Prognostic models in Inflammatory Bowel Disease.
- Author
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Kalla, R, Adams, A T, Ventham, N T, Kennedy, N A, White, R, Clarke, C, Ivens, A, Bergemalm, D, Vatn, S, Lopez-Jimena, B, Consortium, IBD Character, Ricanek, P, Vatn, M H, Söderholm, Johan D, Gomollón, F, Nowak, J K, Jahnsen, J, Halfvarson, J, McTaggart, S, and Ho, G T
- Published
- 2020
- Full Text
- View/download PDF
29. Plasma and antibody glycomic biomarkers of time to HIV rebound and viral setpoint.
- Author
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Giron, Leila B., Papasavvas, Emmanouil, Azzoni, Livio, Xiangfan Yin, Anzurez, Alitzel, Damra, Mohammad, Mounzer, Karam, Kostman, Jay R., Sanne, Ian, Firnhaber, Cynthia S., Tateno, Hiroaki, Qin Liu, Montaner, Luis J., Abdel-Mohsen, Mohamed, Yin, Xiangfan, and Liu, Qin
- Published
- 2020
- Full Text
- View/download PDF
30. The greater inflammatory pathway—high clinical potential by innovative predictive, preventive, and personalized medical approach.
- Author
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Maturo, Maria Giovanna, Soligo, Marzia, Gibson, Greg, Manni, Luigi, and Nardini, Christine
- Abstract
Background and limitations: Impaired wound healing (WH) and chronic inflammation are hallmarks of non-communicable diseases (NCDs). However, despite WH being a recognized player in NCDs, mainstream therapies focus on (un)targeted damping of the inflammatory response, leaving WH largely unaddressed, owing to three main factors. The first is the complexity of the pathway that links inflammation and wound healing; the second is the dual nature, local and systemic, of WH; and the third is the limited acknowledgement of genetic and contingent causes that disrupt physiologic progression of WH. Proposed approach: Here, in the frame of Predictive, Preventive, and Personalized Medicine (PPPM), we integrate and revisit current literature to offer a novel systemic view on the cues that can impact on the fate (acute or chronic inflammation) of WH, beyond the compartmentalization of medical disciplines and with the support of advanced computational biology. Conclusions: This shall open to a broader understanding of the causes for WH going awry, offering new operational criteria for patients' stratification (prediction and personalization). While this may also offer improved options for targeted prevention, we will envisage new therapeutic strategies to reboot and/or boost WH, to enable its progression across its physiological phases, the first of which is a transient acute inflammatory response versus the chronic low-grade inflammation characteristic of NCDs. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
31. GlycA, a Nuclear Magnetic Resonance Spectroscopy Measure for Protein Glycosylation, is a Viable Biomarker for Disease Activity in IBD.
- Author
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Dierckx, Tim, Verstockt, Bram, Vermeire, Séverine, and Weyenbergh, Johan van
- Published
- 2019
- Full Text
- View/download PDF
32. Viewpoint: Toward the Genetic Architecture of Disease Severity in Inflammatory Bowel Diseases.
- Author
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Liefferinckx, Claire and Franchimont, Denis
- Published
- 2018
- Full Text
- View/download PDF
33. N-glycan Characterization by Liquid Chromatography Coupled with Fluorimetry and Mass Spectrometry.
- Author
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Gardner RA, Urbanowicz PA, and Spencer DIR
- Subjects
- Biomarkers, Chromatography, Liquid, Fluorometry, Glycosylation, Humans, Mass Spectrometry, Reproducibility of Results, Polysaccharides chemistry
- Abstract
Human blood plasma and serum have been a source of biomarkers for the indication and progression of many diseases for a few decades now. Human blood plasma is also an excellent source material to enable patients to monitor their health, with a multitude of biomarkers detectable for the assessment of health status. Blood sampling kits are increasingly available for use in the home with no specialist clinical skills required to obtain good quality samples for pathology lab analysis. Many of the proteins that constitute plasma are glycosylated with both N- and O-type glycans. There is increasing interest in the scientific community to identify potential glycan biomarkers or glycan features that are indicative of disease, and in particular disease at an early stage. The quality and reproducibility of glycan analysis data is key in order to identify and utilise glycan-based blood biomarkers with sufficient specificity and sensitivity; hence, the required analytical tools need to be robust. In this chapter, we describe an analytical method for the UHPLC separation of plasma N-glycans which utilizes both glycan reducing terminus fluorophore labeling, to ensure stoichiometric analysis of relative glycan abundance, and online mass spectrometry for glycan identification. Exoglycosidase digestions were employed as example technique to aid and enable structure identification., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2022
- Full Text
- View/download PDF
34. Genome-wide DNA methylation profiling and gut flora analysis in intestinal polyps patients.
- Author
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Liu L, Chen Y, Liu T, Yu J, Ma L, and Wu H
- Subjects
- DNA Methylation, Humans, Intestinal Polyps genetics, Adenoma genetics, Colonic Polyps genetics, Colorectal Neoplasms genetics, Gastrointestinal Microbiome
- Abstract
Background: The intestinal polyp is the precancerous lesion of colorectal cancer. DNA methylation and intestinal microbiota may play an important role in the development of intestinal polyp., Materials and Methods: In this study, we included 10 patients with intestinal polyps who received the colonoscopy examination. We applied the Illumina Human Methylation 850K array to investigate the epigenome-wide DNA methylation patterns. Then, we filtered out the hub genes in the protein-protein interaction networks using functional epigenetic modules analysis. We also analyzed the colonizing bacteria on the surface of polyps compared with those in normal colonic mucosal epithelium with 16S ribosomal DNA sequencing., Results: We identified 323 hypermethylated sites and 7992 hypomethylated sites between intestinal polyps and normal samples. Five hub genes, including CREB1, LPA, SVIL and KRT18, were identified in five modules. Hypomethylation of CREB1 is a candidate marker of colorectal adenoma. Gut microbiota analysis showed that Butyricicoccus was significantly decreased in the intestinal polyp groups., Conclusion: In conclusion, we identified DNA methylation disparities in intestinal polyps compared with normal tissue, of which methylation of CREB1 may hold clinical significance in colorectal cancer progress. Colonizing bacteria in the colonic epithelium might be related to the formation of intestinal polyps., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2021
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- View/download PDF
35. Inflammatory Bowel Disease Meets Systems Biology: A Multi-Omics Challenge and Frontier.
- Author
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Palmieri, Orazio, Mazza, Tommaso, Castellana, Stefano, Panza, Anna, Latiano, Tiziana, Corritore, Giuseppe, Andriulli, Angelo, and Latiano, Anna
- Published
- 2016
- Full Text
- View/download PDF
36. IBD Free Papers.
- Subjects
INTESTINAL diseases ,POLYPS ,DYSPLASIA - Abstract
The article presents abstracts on medical topics which include breath analysis of exhaled volatile organic compound in bowel disease, associated features of inflammatory polyps with malignant progression and low-grade dysplasia (LGD) management in ulcerative colitis patients of Great Britain.
- Published
- 2015
37. Inflammatory Bowel Disease Associates with Proinflammatory Potential of the Immunoglobulin G Glycome.
- Author
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Akmačić, Irena Trbojević, Ventham, Nicholas T., Theodoratou, Evropi, Vučković, Frano, Kennedy, Nicholas A., Krištić, Jasminka, Nimmo, Elaine R., Kalla, Rahul, Drummond, Hazel, Štambuk, Jerko, Dunlop, Malcolm G., Novokmet, Mislav, Aulchenko, Yurii, Gornik, Olga, Campbell, Harry, Baković, Maja Pučić, Satsangi, Jack, and Lauc, Gordan
- Published
- 2015
- Full Text
- View/download PDF
38. Changes to Serum Sample Tube and Processing Methodology Does Not Cause Inter-Individual Variation in Automated Whole Serum N-Glycan Profiling in Health and Disease.
- Author
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Ventham, Nicholas T., Gardner, Richard A., Kennedy, Nicholas A., Shubhakar, Archana, Kalla, Rahul, Nimmo, Elaine R., null, null, Fernandes, Daryl L., Satsangi, Jack, and Spencer, Daniel I. R.
- Subjects
BLOOD serum analysis ,BIOLOGICAL variation ,GLYCANS ,BIOMARKERS ,INFLAMMATORY bowel diseases ,CHROMATOGRAMS - Abstract
Introduction: Serum N-glycans have been identified as putative biomarkers for numerous diseases. The impact of different serum sample tubes and processing methods on N-glycan analysis has received relatively little attention. This study aimed to determine the effect of different sample tubes and processing methods on the whole serum N-glycan profile in both health and disease. A secondary objective was to describe a robot automated N-glycan release, labeling and cleanup process for use in a biomarker discovery system. Methods: 25 patients with active and quiescent inflammatory bowel disease and controls had three different serum sample tubes taken at the same draw. Two different processing methods were used for three types of tube (with and without gel-separation medium). Samples were randomised and processed in a blinded fashion. Whole serum N-glycan release, 2-aminobenzamide labeling and cleanup was automated using a Hamilton Microlab STARlet Liquid Handling robot. Samples were analysed using a hydrophilic interaction liquid chromatography/ethylene bridged hybrid(BEH) column on an ultra-high performance liquid chromatography instrument. Data were analysed quantitatively by pairwise correlation and hierarchical clustering using the area under each chromatogram peak. Qualitatively, a blinded assessor attempted to match chromatograms to each individual. Results: There was small intra-individual variation in serum N-glycan profiles from samples collected using different sample processing methods. Intra-individual correlation coefficients were between 0.99 and 1. Unsupervised hierarchical clustering and principal coordinate analyses accurately matched samples from the same individual. Qualitative analysis demonstrated good chromatogram overlay and a blinded assessor was able to accurately match individuals based on chromatogram profile, regardless of disease status. Conclusions: The three different serum sample tubes processed using the described methods cause minimal inter-individual variation in serum whole N-glycan profile when processed using an automated workstream. This has important implications for N-glycan biomarker discovery studies using different serum processing standard operating procedures. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
39. Promoter methylation of the MGAT3 and BACH2 genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease
- Author
-
Renata D'Incà, Vlatka Zoldoš, Aleksandar Vojta, Jerko Štambuk, Gordan Lauc, Paula Dobrinić, Nicholas A. Kennedy, Ivana Samaržija, Mirna Šimurina, Genadij Razdorov, Jack Satsangi, Ana M. Dias, Marija Klasić, Dora Markulin, Nicholas T. Ventham, Anna Latiano, Ivan Biruš, Vito Annese, Salomé S. Pinho, Irena Trbojević-Akmačić, and Instituto de Investigação e Inovação em Saúde
- Subjects
Male ,0301 basic medicine ,Candidate gene ,lcsh:Medicine ,Inflammatory bowel disease ,Immunoglobulin G ,Epigenesis, Genetic ,chemistry.chemical_compound ,0302 clinical medicine ,Crohn Disease ,Prospective Studies ,Promoter Regions, Genetic ,Colitis, Ulcerative/genetics ,Genetics (clinical) ,Inflammatory Bowel Diseases/genetics ,biology ,Methylation ,N-Acetylglucosaminyltransferases/genetics ,methylation, inflammatory bowel disease ,3. Good health ,Basic-Leucine Zipper Transcription Factors ,030220 oncology & carcinogenesis ,DNA methylation ,Female ,Glycosylation ,lcsh:QH426-470 ,N-Acetylglucosaminyltransferases ,03 medical and health sciences ,Polysaccharides ,Genetics ,medicine ,Humans ,Polysaccharides/metabolism ,Epigenetics ,Molecular Biology ,Gene ,Crohn Disease/genetics ,lcsh:R ,Basic-Leucine Zipper Transcription Factors/genetics ,Sequence Analysis, DNA ,DNA Methylation ,Inflammatory Bowel Diseases ,medicine.disease ,digestive system diseases ,carbohydrates (lipids) ,lcsh:Genetics ,030104 developmental biology ,chemistry ,Case-Control Studies ,Immunology ,Immunoglobulin G/metabolism ,biology.protein ,Colitis, Ulcerative ,Genome-Wide Association Study ,Developmental Biology - Abstract
Background: Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the BACH2, IL6ST, LAMB1, IKZF1, and MGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Methods: Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively. Results: We found significant differences in the methylation levels in the MGAT3 and BACH2 genes between both Crohn's disease and ulcerative colitis when compared to HC. The same pattern of methylation changes was identified for both genes in CD19 + B cells isolated from the whole blood of a subset of the IBD patients. A correlation analysis was performed between the MGAT3 and BACH2 promoter methylation and individual IgG glycans, measured in the same individuals of the two large cohorts. MGAT3 promoter methylation correlated significantly with galactosylation, sialylation, and bisecting GlcNAc on IgG of the same patients, suggesting that activity of the GnT-III enzyme, encoded by this gene, might be altered in IBD. The correlations between the BACH2 promoter methylation and IgG glycans were less obvious, since BACH2 is not a glycosyltransferase and therefore may affect IgG glycosylation only indirectly. Conclusions: Our results suggest that epigenetic deregulation of key glycosylation genes might lead to an increase in pro-inflammatory properties of IgG in IBD through a decrease in galactosylation and sialylation and an increase of bisecting GlcNAc on digalactosylated glycan structures. Finally, we showed that CpG methylation in the promoter of the MGAT3 gene is altered in CD3 + T cells isolated from inflamed mucosa of patients with ulcerative colitis from a third smaller cohort, for which biopsies were available, suggesting a functional role of this glyco-gene in IBD pathogenesis. The authors would like to thank Stephanie Scott for her organizational and administrational contribution. The study has been funded by the EU FP7 grant European Commission IBD-BIOM (contract # 305479), EU FP7 Regional Potential Grant INTEGRA-Life (contract # 315997), European Structural and Investment Funds grant for the Croatian National Centre of Research Excellence in Personalized Healthcare (contract # KK.01.1.1.01.0010), and Croatian Science Foundation grant EpiGlycoIgG (contract # 3361). Financial support from Portugal (PI: SSP): FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/ Ministério da Ciência, Tecnologia e Inovação in the framework of the project (POCI-01/0145-FEDER-016601; PTDC/DTP-PIC/0560/2014) was received. SSP also acknowledges the European Crohn’s and Colitis Organization (ECCO) and the “Broad Medical Research program at Crohn’s and Colitis Foundation of America-CCFA” for funding. SSP acknowledges the Portuguese Group of Study on IBD (GEDII) for funding. A.M.D. [PD/BD/105982/2014] also acknowledges FCT for funding. IBD-BIOM consortium: Daniel Kolarich (Department of Biomolecular Systems, Max Planck Institute of Colloids and Interfaces, Potsdam, Germany), Manfred Wuhrer (Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands; Division of BioAnalytical Chemistry, VU University Amsterdam, Amsterdam, the Netherlands), Dermot P. B. McGovern (F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles), Iain K. Pemberton (IP Research Consulting SAS, Paris, France), Daniel IR Spencer (Ludger Ltd., Culham Science Centre, Oxford, UK, Daryl L. Fernandes (Ludger Ltd., Culham Science Centre, Oxford, UK), Rahul Kalla, Kate O’Leary, Alex T Adams, Hazel Drummond, Elaine Nimmo, Ray Boyapati, David C Wilson (Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK), Ray Doran (Ludger Ltd., Culham Science Centre, Oxford, UK), Igor Rudan (all, Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK), Paolo Lionetti (Paediatric Gastroenterology Unit, AOU Meyer, Viale Pieraccini, Florence, Italy), Natalia Manetti (Department of Medical and Surgical Sciences, Division of Gastroenterology, University Hospital Careggi, Florence, Italy), Fabrizio Bossa (Department of Medical Sciences, Division of Gastroenterology, IRCCS-CSS Hospital, Viale Cappuccini, Rotondo, Italy), Paola Cantoro, Anna Kohn (Division of Gastroenterology, S. Camillo Hospital, Rome, Italy), Giancarlo Sturniolo (Gastrointestinal Unit, University of Padua, Padua, Italy), Silvio Danese (IBD Unit, Humanitas Research Institute, Rozzano, Milan, Italy), Mariek Pierik (Maastricht University Medical Centre (MUMC), Maastricht, the Netherlands), and David C. Wilson (Centre for Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK). This independent research was generously supported by the following grants: EU FP7 research grant IBD-BIOM (contract # 305479) to JS, VA, GL, and VZ; EU FP7 Regional Potential Grant INTEGRA-Life (contract # 315997) to GL and VZ; European Structural and Investment Funds grant for the Croatian National Centre of Research Excellence in Personalized Healthcare (contract # KK.01.1.1.01.0010) to GL and VZ; Croatian Science Foundation grant EpiGlycoIgG (contract # 3361) to VZ; FEDER COMPETE 2020 POCI, Portugal 2020, and Portuguese funds through FCT (contracts # POCI-01/0145-FEDER-016601 and PTDC/DTP-PIC/0560/2014) to SP; and FTC (contract # PD/BD/105982/2014) to AMD.
- Published
- 2018
40. Do changes in DNA methylation mediate or interact with SNP variation? A pharmacoepigenetic analysis.
- Author
-
Fisher, Virginia A., Wang, Lan, Deng, Xuan, Sarnowski, Chloé, Cupples, L. Adrienne, and Liu, Ching-Ti
- Subjects
DNA methylation ,PHARMACOGENOMICS ,SINGLE nucleotide polymorphisms ,FENOFIBRATE ,TRIGLYCERIDES ,THERAPEUTICS - Abstract
Background: In studies with multi-omics data available, there is an opportunity to investigate interdependent mechanisms of biological causality. The GAW20 data set includes both DNA genotype and methylation measures before and after fenofibrate treatment. Using change in triglyceride (TG) levels pre- to posttreatment as outcome, we present a mediation analysis that incorporates methylation. This approach allows us to simultaneously consider a mediation hypothesis that genotype affects change in TG level by means of its effect on methylation, and an interaction hypothesis that the effect of change in methylation on change in TG levels differs by genotype. We select 322 single-nucleotide polymorphism–cytosine-phosphate-guanine (SNP-CpG) site pairs for mediation analysis on the basis of proximity and marginal genome-wide association study (GWAS) and epigenome-wide association study (EWAS) significance, and present results from the real-data sample of 407 individuals with complete genotype, methylation, TG levels, and covariate data. Results: We identified 3 SNP-CpG site pairs with significant interaction effects at a Bonferroni-corrected significance threshold of 1.55E-4. None of the analyzed sites showed significant evidence of mediation. Power analysis by simulation showed that a sample size of at least 19,500 is needed to detect nominally significant indirect effects with true effect sizes equal to the point estimates at the locus with strongest evidence of mediation. Conclusions: These results suggest that there is stronger evidence for interaction between genotype and methylation on change in triglycerides than for methylation mediating the effect of genotype. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
41. Promoter methylation of the <italic>MGAT3</italic> and <italic>BACH2</italic> genes correlates with the composition of the immunoglobulin G glycome in inflammatory bowel disease.
- Author
-
Klasić, Marija, Markulin, Dora, Vojta, Aleksandar, Samaržija, Ivana, Biruš, Ivan, Dobrinić, Paula, Ventham, Nicholas T., Trbojević-Akmačić, Irena, Šimurina, Mirna, Štambuk, Jerko, Razdorov, Genadij, Kennedy, Nicholas A., Satsangi, Jack, Dias, Ana M., Pinho, Salome, Annese, Vito, Latiano, Anna, D'Inca, Renata, IBD consortium, and Lauc, Gordan
- Subjects
PROMOTERS (Genetics) ,IMMUNOGLOBULIN G ,INFLAMMATORY bowel diseases - Abstract
Background: Many genome- and epigenome-wide association studies (GWAS and EWAS) and studies of promoter methylation of candidate genes for inflammatory bowel disease (IBD) have demonstrated significant associations between genetic and epigenetic changes and IBD. Independent GWA studies have identified genetic variants in the
BACH2 ,IL6ST ,LAMB1 ,IKZF1 , andMGAT3 loci to be associated with both IBD and immunoglobulin G (IgG) glycosylation. Methods: Using bisulfite pyrosequencing, we analyzed CpG methylation in promoter regions of these five genes from peripheral blood of several hundred IBD patients and healthy controls (HCs) from two independent cohorts, respectively. Results: We found significant differences in the methylation levels in theMGAT3 andBACH2 genes between both Crohn's disease and ulcerative colitis when compared to HC. The same pattern of methylation changes was identified for both genes in CD19+ B cells isolated from the whole blood of a subset of the IBD patients. A correlation analysis was performed between theMGAT3 andBACH2 promoter methylation and individual IgG glycans, measured in the same individuals of the two large cohorts.MGAT3 promoter methylation correlated significantly with galactosylation, sialylation, and bisecting GlcNAc on IgG of the same patients, suggesting that activity of the GnT-III enzyme, encoded by this gene, might be altered in IBD. The correlations between theBACH2 promoter methylation and IgG glycans were less obvious, sinceBACH2 is not a glycosyltransferase and therefore may affect IgG glycosylation only indirectly. Conclusions: Our results suggest that epigenetic deregulation of key glycosylation genes might lead to an increase in pro-inflammatory properties of IgG in IBD through a decrease in galactosylation and sialylation and an increase of bisecting GlcNAc on digalactosylated glycan structures. Finally, we showed that CpG methylation in the promoter of theMGAT3 gene is altered in CD3+ T cells isolated from inflamed mucosa of patients with ulcerative colitis from a third smaller cohort, for which biopsies were available, suggesting a functional role of this glyco-gene in IBD pathogenesis. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
42. Protein N-Glycosylation in Cardiovascular Diseases and Related Risk Factors.
- Author
-
Gudelj, Ivan and Lauc, Gordan
- Abstract
Purpose of Review: Protein glycosylation has been observed to associate with different diseases, including cardiovascular diseases (CVDs). Most of these observations are related to O-glycosylation, yet N-glycosylation changes have recently gained more attention.Recent Findings: N-Glycosylation alterations are associated with CVDs and play an important role in disease development: directly and indirectly through risk factors associated with the disease.Summary: The changes of N-glycosylation are a new risk factor for CVDs and have significant biomarker potential for disease development, progression, and therapy monitoring. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
43. OC-010 Epigenome-wide dna methylation profiling in inflammatory bowel disease
- Author
-
KR O’Leary, Nicholas A. Kennedy, Rahul Kalla, Elaine R. Nimmo, J. Satsangi, Alex Adams, Nicholas T. Ventham, and David C. Wilson
- Subjects
business.industry ,CD14 ,Gastroenterology ,Methylation ,Epigenome ,medicine.disease ,Inflammatory bowel disease ,Differentially methylated regions ,CpG site ,DNA methylation ,Immunology ,Medicine ,Epigenetics ,business - Abstract
Introduction Epigenetic alterations including DNA methylation may provide important insights into gene-environment interaction in complex immune diseases such as inflammatory bowel disease (IBD). Whilst whole tissue methylation changes may provide clinically useful biomarkers, epigenetic changes are cell-type specific. This study aimed to characterise the circulating methylome in IBD, and relate changes seen in whole blood to the methylation profile in separated leucocytes, gene expression data, as well as our previous data in childhood-onset disease. 1 Method The Illumina 450k array was used to assess whole blood leucocyte DNA methylation at over 485,000 CpG sites across the genome in 240 patients (121 Crohn’s disease [CD], 119 ulcerative colitis [UC]) and 191 controls. Differentially methylated sites discovered in whole blood were investigated in immunomagnetically separated leucocytes (CD4 + and CD8 + lymphocytes, CD14 + monocytes). Results There were 439 differentially methylated positions (DMPs) meeting epigenome wide significance as defined as a Holm corrected p value of –7 ) in IBD cases versus control. No markers were significantly different between CD and UC. There were 55 differentially methylated regions (DMRs) with unidirectional methylation change in 3 or more adjacent markers each achieving False Discovery Rate significance of p There was significant enrichment of methylation alteration around known susceptibility loci. 2 Linear Discriminant analysis using two CpG sites discriminated IBD cases and controls with high accuracy (area under curve 0.87). Established as well as novel pathways pertinent to disease pathogenesis are strongly implicated. The most significantly DMP in whole blood (RPS6KA2 [corrected p = 1.2 × 10 –16 ] was also hypomethylated in monocytes in UC (uncorrected p = 3.5 × 10 –6 ). The most significant DMR,VMP1/miR21 (most significant probe corrected p = 2 × 10 –14 ) strongly replicates the same finding in our previous study. The gene encoding Beta-2 Integrin (ITGB2) was a hypermethylated DMR in IBD and more specifically CD (most significant probe corrected p = 3.3 × 10 –5 ) compared with controls. Conclusion This is the most detailed characterisation of the epigenome carried out in IBD to date and includes novel data exploring the circulating methylome in UC. The findings strongly validate this approach in complex disease, replicate and expand previous data, and provide clear translational opportunities. Disclosure of interest N. Ventham Grant/Research Support from: EC grant IBD-BIOM, Conflict with: Abbvie, MSD speakers fees, N. Kennedy Grant/Research Support from: Wellcome Trust, Conflict with: Abbvie, MSD, Warner Chilcott, Ferring speakers fees. Shire Travel bursay, A. Adams: None Declared, R. Kalla: None Declared, K. O’Leary: None Declared, IBD BIOM consortium: None Declared, D. Wilson Grant/ Research Support from: MRC, CICRA, and EC grant IBD-BIOM, Consultant for: Pfizer, Conflict with: MSD investigator grant, MSD speaker fee, and Ferring speaker fee, E. Nimmo Grant/ Research Support from: EC grant IBD-BIOM, CSO, J. Satsangi Grant/ Research Support from: EC grant IBD-BIOM, Wellcome, CSO, MRC, Consultant for: Takeda, Conflict with: MSD speaker fees. SHire travelling expenses. References Adams AT, et al . IBD 2014;20(10):1784–93 Jostins L, et al . Nature 2012; 491(7422):119–24
- Published
- 2015
44. Novel Perspectives in Economics of Personalized Medicine and Healthcare Systems
- Author
-
Romina Pržiklas Družeta, PhD and Romina Pržiklas Družeta, PhD
- Subjects
- Precision medicine--Economic aspects
- Abstract
This book represents a valuable interdisciplinary contribution created to fill an existing gap in the field of health economics and healthcare systems. The book brings the latest insights from the growing field of health economics and healthcare systems. It deals with various economic, technological, sociological, ethical, legal and philosophical implications and questions arising from the development and implementation of personalized medicine. It is unprecedented in combining practical guidelines for the use of economic tools and techniques with an analysis of the current process of decision-making in the health service sector. The book also provides several insights into the factors that determine human health, the socioeconomic aspects of population aging and the social implications of the evolving burden of disease. Some contributions are highly innovative and cover extremely relevant branches of medicine such as oncology, neurology and endocrinology. In addition, in a brave, yet professional and sovereign manner, the book covers the issue of biological predictors of health outcomes; though they are currently mainly used as global analytical methods, they are yet to be applied or have only recently been applied in clinical medicine. Further, it provides an example from traditional Korean medicine, a proven and valuable tool for personalized medical healthcare. This edition is unique in the sense that 30 chapters were written by 41 authors, all of them experts in their respective fields of research. The authors hail from Croatia, Hungary, South Korea and the United States. The volume is intended to serve as valuable teaching material for university students, as well as a reference book for research scholars, policymakers, business executives, health managers, physicians and freelance readers.
- Published
- 2022
45. Therapeutic Effects of Resveratrol in Inflammatory Bowel Diseases: Shedding Light on the Role of Cellular and Molecular Pathways
- Author
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Talebi, Marjan, Talebi, Mohsen, Farkhondeh, Tahereh, and Samarghandian, Saeed
- Published
- 2022
- Full Text
- View/download PDF
46. A novel glycosidase plate-based assay for the quantification of galactosylation and sialylation on human IgG
- Author
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Rebello, Osmond D., Gardner, Richard A., Urbanowicz, Paulina A., Bolam, David N., Crouch, Lucy I., Falck, David, and Spencer, Daniel I. R.
- Published
- 2020
- Full Text
- View/download PDF
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