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Genetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative Colitis

2020Journal article Open access
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dc.contributor.authorPereira, Márcia S.
dc.contributor.authorDurães, Cecília
dc.contributor.authorCatarino, Telmo A.
dc.contributor.authorCosta, José L.
dc.contributor.authorCleynen, Isabelle
dc.contributor.authorNovokmet, Mislav
dc.contributor.authorKrištić, Jasminka
dc.contributor.authorŠtambuk, Jerko
dc.contributor.authorConceição-Neto, Nádia
dc.contributor.authorMachado, José C.
dc.contributor.authorMarcos-Pinto, Ricardo
dc.contributor.authorMagro, Fernando
dc.contributor.authorVermeire, Séverine
dc.contributor.authorLauc, Gordan
dc.contributor.authorLago, Paula
dc.contributor.authorPinho, Salomé S.
dc.date.accessioned2021-11-16T15:17:14Z
dc.date.available2021-11-16T15:17:14Z
dc.date.issued2020
dc.description.abstractObjectives: The impact of genetic variants (single nucleotide polymorphisms [SNPs]) in the clinical heterogeneity of ulcerative colitis (UC) remains unclear. We showed that patients with UC exhibit a deficiency in MGAT5 glycogene transcription in intestinal T cells associated with a hyperimmune response. Herein, we evaluated whether MGAT5 SNPs might functionally impact on T cells glycosylation and plasma IgG glycome in patients with UC, as well as in UC clinical outcomes. Methods: Three selected MGAT5 SNPs (rs3814022, rs4953911, and rs1257220), previously associated with severity of autoimmune disease or with plasma glycome composition in healthy individuals, were functionally evaluated in patients with UC through analysis of MGAT5 mRNA levels in colonic (n = 14) and circulating (n = 24) T cells and through profiling the plasma IgG Fc glycosylation (n = 152). MGAT5 SNPs were genotyped in 931 patients with UC from 2 European cohorts and further associated with patients' prognosis. Targeted next-generation sequencing for MGAT5 coding and regulatory regions was also performed. Results: MGAT5 SNPs were shown to be functionally associated with low transcription levels of MGAT5 in colonic and circulating T cells from patients with UC and with agalactosylation of IgGs, often associated with a proinflammatory phenotype. The SNPs rs3814022 and rs4953911 were further associated with the need of biologics. Next-generation sequencing data further revealed a combination of MGAT5 SNPs that stratify patients with UC according to their severity. Discussion: Our results revealed that MGAT5 SNPs have a phenotypic impact on T cells glycosylation and in plasma IgG glycome composition associated with UC pathogenesis. MGAT5 SNPs display a tendency in the association with a worse disease course in patients with UC.pt_PT
dc.description.sponsorshipFinancial support from Portugal: Institute of Molecular Pathology and Immunology of University of Porto (IPATIMUP) integrates the i3S research unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT). This article is a result of the project NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020) under the PORTUGAL 2020 Partnership Agreement through the European Regional Development Fund (ERDF). This work was also funded by 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 projects (POCI-01/0145-FEDER-016601; PTDC/DTP-PIC/0560/2014; POCI-01-0145-FEDER-028772). S.S.P. also acknowledges the European Crohn's and Colitis Organization (ECCO) for ECCO Grant; the Broad Medical Research Program at the Crohn's and Colitis Foundation of America, and the Portuguese Group of Study in IBD (GEDII) for funding. S.S.P. also acknowledges the US Department of Defense, US Army Medical Research Acquisition Activity, FY18 Peer Reviewed Medical Research Program Investigator-Initiated Research Award (award number W81XWH1920053). M.S.P. (SFRH/BD/110148/2015) acknowledges FCT for funding.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPereira MS, Durães C, Catarino TA, et al. Genetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative Colitis. Clin Transl Gastroenterol. 2020;11(4):e00166. doi:10.14309/ctg.0000000000000166pt_PT
dc.identifier.doi10.14309/ctg.0000000000000166pt_PT
dc.identifier.issn2155-384X
dc.identifier.urihttp://hdl.handle.net/10400.16/2565
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWolters Kluwer Healthpt_PT
dc.relation.publisherversionhttps://journals.lww.com/ctg/Fulltext/2020/04000/Genetic_Variants_of_the_MGAT5_Gene_Are.13.aspxpt_PT
dc.titleGenetic Variants of the MGAT5 Gene Are Functionally Implicated in the Modulation of T Cells Glycosylation and Plasma IgG Glycome Composition in Ulcerative Colitispt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPagee00166pt_PT
oaire.citation.titleClinical and Translational Gastroenterologypt_PT
oaire.citation.volume11pt_PT
person.familyNameMarcos-Pinto
person.familyNameLAGO VIEIRA DOS SANTOS
person.givenNameRicardo
person.givenNamePAULA MARIA
person.identifier.ciencia-id5514-3FC4-9C62
person.identifier.orcid0000-0001-9695-8261
person.identifier.ridK-4612-2013
person.identifier.scopus-author-id53984773600
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication7af2c629-e150-47fc-b0e1-69831696045b
relation.isAuthorOfPublicationabe823e2-57bc-45ab-9ab5-a59cfe48dab5
relation.isAuthorOfPublication.latestForDiscovery7af2c629-e150-47fc-b0e1-69831696045b

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