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Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy.

ABSTRACT: Humans have circulating antibodies against diverse glycans containing N-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the CMAH gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a drug containing polyclonal IgG glycoproteins commonly used as an immunosuppressant in human transplantation and autoimmune diseases. In type-1 diabetes patients, infusion of Neu5Gc-glycosylated ATG caused increased global anti-Neu5Gc response. Here, for the first time we explore changes in anti-Neu5Gc IgG repertoire following the immunization elicited by ATG, compared with the basal antibodies repertoire that reflect exposure to dietary-Neu5Gc. We used glycan microarrays with multiple Neu5Gc-glycans and controls to elucidate eventual differences in ATG-elicited repertoire, before/after ATG administration and track their kinetics (0, 1, 18 and 24 months). Response of all basal-pre-existing Neu5Gc-specific antibodies rapidly increased. This response peaked at one month post-ATG, with enhanced affinity, then resolved at 18-24 months. Induced-antibodies showed expanded diversity and de-novo recognition of different Neu5Gc-glycans, including endogenous glycolipids, that was further validated by affinity-purified anti-Neu5Gc antibodies from patients' sera. These findings strongly suggest that ATG-induced anti-Neu5Gc IgGs represent a secondary exposure to this dietary carbohydrate-antigen in humans, with immune memory. Given their modified recognition patterns, ATG-evoked anti-Neu5Gc antibodies could potentially mediate biological effects different from pre-existing antibodies.

SUBMITTER: Amon R

PROVIDER: S-EPMC5762506 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy.

Amon Ron R Ben-Arye Shani Leviatan SL Engler Limor L Yu Hai H Lim Noha N Berre Ludmilla Le LL Harris Kristina M KM Ehlers Mario R MR Gitelman Stephen E SE Chen Xi X Soulillou Jean-Paul JP Padler-Karavani Vered V

Oncotarget 20171211 68

Humans have circulating antibodies against diverse glycans containing <i>N</i>-glycolylneuraminic acid (Neu5Gc) due to function-loss mutation of the <i>CMAH</i> gene. This xenogenic non-human carbohydrate is abundant in red meat, xenografts and biotherapeutics. Low levels of diet-derived Neu5Gc is also present on normal human endothelial cells, and together with anti-Neu5Gc antibodies could potentially mediate "xenosialitis" chronic-inflammation. Rabbit anti-human thymocyte globulin (ATG) is a d ...[more]

PMID: 29348821

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Project description:MotivationGlycan microarrays are capable of illuminating the interactions of glycan-binding proteins (GBPs) against hundreds of defined glycan structures, and have revolutionized the investigations of protein-carbohydrate interactions underlying numerous critical biological activities. However, it is difficult to interpret microarray data and identify structural determinants promoting glycan binding to glycan-binding proteins due to the ambiguity in microarray fluorescence intensity and complexity in branched glycan structures. To facilitate analysis of glycan microarray data alongside protein structure, we have built the Glycan Microarray Database (GlyMDB), a web-based resource including a searchable database of glycan microarray samples and a toolset for data/structure analysis.ResultsThe current GlyMDB provides data visualization and glycan-binding motif discovery for 5203 glycan microarray samples collected from the Consortium for Functional Glycomics. The unique feature of GlyMDB is to link microarray data to PDB structures. The GlyMDB provides different options for database query, and allows users to upload their microarray data for analysis. After search or upload is complete, users can choose the criterion for binder versus non-binder classification. They can view the signal intensity graph including the binder/non-binder threshold followed by a list of glycan-binding motifs. One can also compare the fluorescence intensity data from two different microarray samples. A protein sequence-based search is performed using BLAST to match microarray data with all available PDB structures containing glycans. The glycan ligand information is displayed, and links are provided for structural visualization and redirection to other modules in GlycanStructure.ORG for further investigation of glycan-binding sites and glycan structures.Availability and implementationhttp://www.glycanstructure.org/glymdb.Supplementary informationSupplementary data are available at Bioinformatics online.

Project description:To explore the factors (including knowledge and attitude) influencing the decision to follow a low-carbohydrate diet (LCD) or not in a sample of the UK population. An online questionnaire was distributed electronically to adults who had either followed LCD or not (February-December 2019). Demographics and self-reported "LCD-status" (current, past and non-follower) were collected. Multivariable linear regression was used with carbohydrate knowledge, dietary guideline agreement and theory of planned behaviour (TPB) constructs (all as predictors) to explain the intention to follow a LCD (outcome). Respondents (n = 723, 71% women, median age 34; 85% white-ethnicity) were either following (n = 170, 24%) or had tried a LCD in the preceding 3 months (n = 184, 25%). Current followers had lower carbohydrate knowledge scores (1-2 point difference, scale - 11 to 11) than past and non-followers. A majority of current LCD followers disagreed with the EatWell guide recommendations "Base meals on potatoes, bread, rice and pasta, or other starchy carbohydrates. Choose whole grains where possible" (84%) and "Choose unsaturated oils and spreads and eat in small amounts such as vegetable, rapeseed, olive and sunflower oils" (68%) compared to past (37%, 10%, respectively) and non-followers (16%, 8%, respectively). Weight-loss ranked first as a motivation, and the internet was the most influencial source of information about LCDs. Among LCD-followers, 71% reported ≥ 5% weight loss, and over 80% did not inform their doctor, nurse, or dietitian about following a diet. Approximately half of LCD followers incorporated supplements to their diets (10% used multivitamin/mineral supplements), despite the restrictive nature of the diet. TPB constructs, carbohydrate knowledge, and guideline agreement explained 60% of the variance for the intention to follow a LCD. Attitude (std-β = 0.60), perceived behavioural control (std-β = 0.24) and subjective norm (std-β = 0.14) were positively associated with the intention to follow a LCD, while higher knowledge of carbohydrate, and agreeing with national dietary guidelines were both inversely associated (std-β = - 0.09 and - 0.13). The strongest primary reason behind UK adults' following a LCD is to lose weight, facilitated by attitude, perceived behavioural control and subjective norm. Higher knowledge about carbohydrate and agreement with dietary guidelines are found among people who do not follow LCDs.

Dataset Information

Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy.

Publications

Glycan microarray reveal induced IgGs repertoire shift against a dietary carbohydrate in response to rabbit anti-human thymocyte therapy.

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