Abstract
Antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) are involved in destruction of thyroid tissue in Hashimoto’s thyroiditis (HT). N-glycosylation of the Fc fragment affects the effector functions of IgG by enhancing or suppressing the cytotoxicity effect. The aim of the present study was to assess the impact of HT-specific IgG glycosylation in ADCC and CDC, using in vitro models. The normal thyroid Nthy-ori 3-1 cell line and thyroid carcinoma FTC-133 cells were used as the target cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors and the HL-60 human promyelotic leukemia cell line served as the effector cells. IgG was isolated from sera of HT and healthy donors and then treated with α2-3,6,8-neuraminidase to cut off sialic acids (SA) from N-glycans. We observed more intensive cytotoxicity in the presence of IgG from HT patients than in the presence of IgG from healthy donors. Removal of SA from IgG N-glycans increased ADCC intensity and reduced CDC. We conclude that the enhanced thyrocyte lysis resulted from the higher anti-TPO content in the whole IgG pool of HT donors and from altered IgG glycosylation in HT autoimmunity.
Highlights
Hashimoto’s thyroiditis (HT), an autoimmune thyroid disease (AITD), is characterized by infiltration of thyroid antigen-reactive T cells and by the presence of autoantibodies against thyroid antigens
A study of an in vitro model consisting of primary human thyroid cells used as the target cells, serum samples from HT, Graves’ disease (GD) and primary myxoedema donors used as autoantibody sources, and Peripheral blood mononuclear cells (PBMCs) serving as the effector cells confirmed the significance of thyroid-specific antibodies in the antibody-dependent cell-mediated cytotoxicity (ADCC) process
TPO surface expression was significantly higher in the FTC-133 cell line (p = 0.03; Figure 2C), raising the question of whether the expected cytotoxic effect in the planned ADCC and complement-dependent cytotoxicity (CDC) assays will depend on TPO surface expression
Summary
Hashimoto’s thyroiditis (HT), an autoimmune thyroid disease (AITD), is characterized by infiltration of thyroid antigen-reactive T cells and by the presence of autoantibodies against thyroid antigens (thyroid peroxidase, TPO; thyroglobulin, Tg). Studies of in vitro models have shown that the mechanisms of thyroid tissue damage in AITD rely on antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) triggered by autoantibodies characteristic for AITD. A study of an in vitro model consisting of primary human thyroid cells used as the target cells, serum samples from HT, Graves’ disease (GD) and primary myxoedema donors used as autoantibody sources, and PBMC serving as the effector cells confirmed the significance of thyroid-specific antibodies in the ADCC process. Pre-incubation of HT IgG with purified TPO significantly decreased specific cell lysis, demonstrating that CDC is mediated by anti-TPO IgG. Effective lysis of thyrocytes by CDC was observed when the cells were incubated with anti-TPO followed by guinea pig serum used as complement source [7]
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