Antibody-dependent cell-mediated cytotoxicity against orbital target cells in thyroid-associated ophthalmopathy and related disorders; close relationship between serum cytotoxic antibodies and parameters of eye muscle dysfunction

Abstract

We have carried out tests for antibody-dependent cell-mediated cytotoxicity (ADCC) against extra ocular muscle (EOM), Müller's muscle, orbital fibroblasts and skeletal muscle in patients with thyroid-associated ophthalmopathy (TAO) and related eye disorders. Cytotoxicity was measured as lactate dehydrogenase (LDH) release and results expressed as % cytotoxicity. Tests were positive, with EOM cells, in 65% of patients with TAO, 75% with ocular myopathy, a variant of TAO in which periorbital inflammation is minimal, 50% with euthyroid Graves' disease defined as ophthalmopathy associated with subclinical thyroiditis and in 50% of patients with stable lid lag and retraction but no other signs of progressive ophthalmopathy, but in only 13% of patients with Graves' hyperthyroidism without ophthalmopathy, 10% with Hashimoto's thyroiditis and 14% of patients with other thyroid disorders. Tests were positive, with Müller's muscle cells, in 40% of patients with TAO, 25% with ocular myopathy, 40% with euthyroid Graves' disease, 44% with lid lag, 19% with Graves'hyperthyroidism, 50% with Hashimoto's thyroiditis and in 37.5% of patients with other thyroid disorders. When skeletal muscle cells were used as target, tests were positive in 13% of patients with TAO, 31% with lid lag, 25% with Graves' hyperthyroidism and in 29% of patients with Hashimoto's thyroiditis, but in no patient with euthyroid Graves' disease or other thyroid disorders. Tests were negative in all patients and normals tested when EOM-derived fibroblasts were used as targets in ADCC. A significant positive correlation between % cytotoxicity against EOM cells and the severity of the eye muscle dysfunction expressed as an eye muscle index, was observed in patients with TAO. There was a significant negative correlation between the duration of eye disease and % cytotoxicity against EOM cells, suggesting higher titers of cytotoxic antibodies in the early stages of TAO. There was no correlation between % cytotoxicity and serum level of anti-TSH receptor antibodies, measured in a radioreceptor assay. These findings suggest that autoimmunity against Müller's muscle may play a role in the pathogenesis of persistent lid lag and retraction. The nature of the EOM and Müller's muscle autoantigens recognized by cytotoxic antibodies in the serum of patients with TAO and related eye disorders is unknown.

Association Between Keratoconus and Thyroid Gland Dysfunction: A Cross-Sectional Case–Control Study

“…The association of thyroid and ophthalmopathy was described in the literature. 15 The results of this study showed that thyroid gland dysfunction prevalence was 5.35% in patients with keratoconus and 1.1% in the control group. Our results for the control group were less than the previous reported prevalence of thyroid dysfunction in adults in the general population (2%).…”

Autophagy Plays a Critical Role in ChLym-1-Induced Cytotoxicity of Non-Hodgkin’s Lymphoma Cells

“…The ability of chLym-1 to mediate ADCC after autophagy inhibition was assessed employing human peripheral blood mononuclear cells (PBMC) as effecter cells, and measured by a 5 h LDH release assay [25]. Pretreated with autophagy inhibitor 3-MA and NH 4 Cl for 12 h, Raji cells were incubated with 10 µg/ml of chLym-1 and autophagy suppressor 3-MA or NH 4 Cl in the presence of PBMC at a ratio of 1∶20, 1∶40 or 1∶60 for 5 h. For further confirm the role of autophagy in chLym-1-induced ADCC, siRNA anti-ATG5 was transferred into Raji cells 48 h before ADCC assay.…”

Autoantibodies with Different Level of Specificity and Functionality in the Pathogenesis and Diagnostics of Autoimmune Thyroid Disorders

“…ТПО -активный "участник" процессов комплемент зависимой и АТ опосредо ванной цитотоксичности. При этом анти ТГ, обла дая по природе цитотоксическим потенциалом, в от личие от анти ТПО участия в комплемент зависи мом АТ опосредованном цитолизе ткани ЩЖ, как правило, не принимают [24]. Важно подчеркнуть, что в кровотоке ТГ обнаруживается в значительно больших концентрациях по сравнению с ТПО, при этом иммуногенный потенциал ТГ также значитель но более выражен, чем у ТПО.…”