Dataset Information

Decreased IgG core fucosylation, a player in antibody-dependent cell-mediated cytotoxicity, is associated with autoimmune thyroid diseases

ABSTRACT: Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins (Igs) and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells (PBMCs) glycosylation with AITD and the influence of genetic background. The study revealed an inverse association of IgG core fucosylation with TPOAb and PBMCs antennary α1,2 fucosylation with AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity (ADCC) associated with TPOAb levels

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood

SUBMITTER: Marta Ząbczyńska

LAB HEAD: Ewa Pocheć

PROVIDER: PXD015684 | Pride | 2020-02-14

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	1stbiologicalreplication.dat	Other
	1stbiologicalreplication.mzid	Mzid
	2ndbiologicalreplication.dat	Other
	2ndbiologicalreplication.mzid	Mzid
	3rdbiologicalreplication.dat	Other

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Publications

Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases.

Martin Tiphaine C TC Šimurina Mirna M Ząbczyńska Marta M Martinic Kavur Marina M Rydlewska Magdalena M Pezer Marija M Kozłowska Kamila K Burri Andrea A Vilaj Marija M Turek-Jabrocka Renata R Krnjajić-Tadijanović Milena M Trofimiuk-Müldner Małgorzata M Ugrina Ivo I Lityńska Anna A Hubalewska-Dydejczyk Alicja A Trbojevic-Akmacic Irena I Lim Ee Mun EM Walsh John P JP Pocheć Ewa E Spector Tim D TD Wilson Scott G SG Lauc Gordan G

Molecular & cellular proteomics : MCP 20200205 5

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear ...[more]

PMID: 32024769

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Project description:BACKGROUND: Novel biomarkers are urgently needed to distinguish between benign and malignant thyroid nodules and detect thyroid cancer in the early stage. The associations between serum IgG N-glycosylation and thyroid cancer risk have been revealed. We aimed to explore the potential of IgG N-glycan traits as biomarkers in the differential diagnosis of thyroid cancer.METHODS: Plasma IgG N-glycome analysis was applied to a discovery cohort followed by independent validation. IgG N-glycan profiles were obtained using a robust quantitative strategy based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. IgG N-glycans were relatively quantified, and classification performance was evaluated based on directly detected and derived glycan traits.RESULTS: Four directly detected glycans were significantly changed in thyroid cancer patients compared to that in non-cancer controls. Derived glycan traits and a classification glycol-panel were generated based on the directly detected glycan traits. In the discovery cohort, derived trait BN (bisecting type neutral N-glycans) and the glyco-panel showed potential in distinguishing between thyroid cancer and non-cancer controls with AUCs of 0.920 and 0.917, respectively. The diagnostic potential was further validated. Derived trait BN and the glycol-panel displayed “accurate” performance (AUC>0.8) in discriminating thyroid cancer from benign thyroid nodules and healthy controls in the validation cohort. Meanwhile, derived trait BN and the glycol-panel also showed diagnostic potential in detecting early-stage thyroid cancer.CONCLUSIONS: IgG N-glycome analysis revealed N-glycomic differences that allow classification of thyroid cancer from non-cancer controls. Our results suggested that derived trait BN and the classification glyco-panel rather than single N-glycans may serve as candidate biomarkers for further validation.