N-glycosylation of CD4+ T cell changes with the development in Graves' disease and is sensitive to methimazole treatment

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 8; p. 130824
• Main Authors: Trzos, Sara, Szewczyk, Marta, Link-Lenczowski, Paweł, Sokołowski, Grzegorz, Trofimiuk-Müldner, Małgorzata, Bocian, Katarzyna, Pocheć, Ewa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2025
• Subjects: Adult; Antithyroid Agents - pharmacology; Antithyroid Agents - therapeutic use; Autoimmunity; CD4+ T cells; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Female; Glycosylation - drug effects; Glycosyltransferases; Graves Disease - drug therapy; Graves Disease - immunology; Graves Disease - metabolism; Graves Disease - pathology; Graves' disease; Humans; Male; Methimazole; Methimazole - pharmacology; Methimazole - therapeutic use; Middle Aged; N-glycosylation; Polysaccharides - metabolism; Autoimmunity; Methimazole; CD4+ T cells; Graves' disease; N-glycosylation; Glycosyltransferases; CD4(+) T cells
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130824

Graves' disease (GD) is one of the most common autoimmune disorders. Helper T (Th) cells, whose surface receptors are rich in glycans, are involved in the GD pathomechanism. N-glycosylation is altered during autoimmunity and can be modulated by pharmacotherapy. We hypothesized that changes in Th glycosylation accompany GD, and the glycome of these cells is sensitive to methimazole therapy. The study group consisted of patients with Graves' disease before (GD) and after (GD/T) restoring euthyroidism as a result of methimazole therapy. In the control group, healthy donors were recruited. Th cells were isolated from PBMCs and sorted into a subpopulation of CD4+CD25− cells and those expressing the CD25 late activation marker (CD4+CD25+). MALDI-Tof MS was used for analysis of N-linked glycans, and the expression of glycosyltransferases was determined by RT-qPCR. The N-glycosylation profile of CD4+ cell subpopulations differed in the ratio of the complex-to-oligomannose N-glycans in GD. Complex N-glycans are partially replaced by oligomannose forms, and their structure is shortened by agalactosylation in CD4+CD25− cells from GD. The rearrangement of N-glycans in CD4+CD25+ cells has the opposite direction, namely the ratio is shifted towards complex structures in GD. The changes in the N-glycan profile were reflected partly in MGAT5 and FUT8 expression. Methimazole to some extent normalized the glycosyltransferase levels and affected the N-linked glycans profile. Our study shows N-glycosylation changes in CD4+ T cells in GD development and methimazole therapy for the first time. Further studies are needed to determine the functional aspect of the identified glycosylation changes in thyroid autoimmunity. [Display omitted] •N-glycan structure of CD4+ T CD25− and CD25+ cells is differently rebuilt during GD.•Oligomannose N-glycans are preferred in CD4+CD25− cells in GD.•Complex-type N-gycans are more abundant in CD4+CD25+ cells in GD development.•Methimazole partially reverses N-glycosylation changes in CD4+ T cells.•Reduced FUT8 expression is reflected in the lower level of fucosylated N-glycans.