Glycosylation of Anti-Thyroglobulin IgG1 and IgG4 Subclasses in Thyroid Diseases

Abstract

<b><i>Objective:</i></b> Thyroglobulin antibodies (TgAb), principally comprising immunoglobulin G (IgG), are frequently found in healthy individuals. Previously, we showed that the glycosylation levels of TgAb IgG differed across various thyroid diseases, suggesting an important role of glycosylation on antibodies in the pathogenesis of thyroid diseases. Since IgG1 and IgG4 are the primary TgAb IgG subclasses, this study aimed to investigate the glycosylation of TgAb IgG1 and IgG4 subclasses in thyroid diseases. <b><i>Methods:</i></b> TgAb IgG was purified by affinity chromatography from the serum of patients with Hashimoto’s thyroiditis (HT) (<i>n</i> = 16), Graves’ disease (GD) (<i>n</i> = 8), papillary thyroid carcinoma (PTC) (<i>n</i> = 6), and PTC with histological lymphocytic thyroiditis (PTC-T) (<i>n</i> = 9) as well as healthy donors (<i>n</i> = 10). TgAb IgG1 and IgG4 concentrations were determined by enzyme-linked immunosorbent assay, and a lectin microassay was used to assess TgAb IgG1 and IgG4 glycosylation. <b><i>Results:</i></b> Significantly elevated mannose, sialic acid, and galactose levels on TgAb IgG1 were found in HT and PTC patients compared to GD patients and healthy controls (all <i>p</i> &#x3c; 0.05). The mannose, sialic acid, and core fucose levels on TgAb IgG1 in PTC-T patients were higher than in healthy controls (all <i>p</i> &#x3c; 0.05). Additionally, TgAb IgG1 from PTC-T patients exhibited lower sialylation than that from patients with PTC and higher fucosylation than that from patients with HT (both <i>p</i> &#x3c; 0.05). However, TgAb IgG4 glycosylation did not differ among the five groups (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> Our study describes different distributions of TgAb IgG1 glycosylation in various thyroid diseases. The aberrantly increased glycosylation levels of TgAb IgG1 observed in HT, PTC, and PTC-T might be indicative of immune disorders and participate in the pathogenesis of these diseases.