Antithyrotropin Receptor Antibody: An Update

Akamizu, Takashi

doi:10.1089/10507250152740966

Cited by 27 publications

(19 citation statements)

References 129 publications

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“…As TRAb are considered the hall markers of GD [41,42], their persistence in the blood of patients treated with ATD may indicate on going active disease. For this reason many investigators are focused on the possible role played by TRAb as predictors of GD outcome [10-13, 20, 43, 44].…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

et al. 2007

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Abstract. In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p<0.001); a titer equal to (or) more than 46.5 UI/L could identify patients who had never achieved long-term remission with a sensitivity of 52% and a specificity of 78%. Also fall rate of TRAb at 6 months of follow up and after therapy withdrawal were useful to predict the final outcome (p<0.001). At 6 months of follow up the time of therapy withdrawal, a decrease of TRAb lower than 52.3% or even its increase could identify patients who had never achieved permanent remission with a sensitivity of 55% and a specificity of 79.1%. No single parameter among TRAb, satisfactory identified a sub-set of patients who achieved long remission. Accordingly to our data, the best result in predicting long term remission is probably given by the presence of at least one of the two features evaluated at 6 months (TRAb titer and/or percentage of TRAb fall rate), with a sensitivity of 63% and specificity of 88%. TRAb titers evaluated both at the onset of hyperthyroidism that at 6 months of therapy or their rate of fall at 6 months and at ATD withdrawal are predictors of outcome. However, the presence of at least one, between titers of TRAb or their rate of fall at six months, resulted to be the best predictor of remission with the higher sensitivity and specificity.

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Section: Discussionmentioning

confidence: 99%

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

et al. 2007

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“…In patients with GD, it is assumed that such antibodies stimulate receptor activity and, hence, thyroid function. However, albeit highly sensitive and specific, TBII assays do not discriminate between in vivo stimulating antibodies (responsible for GD), blocking-type antibodies (found rarely in women with Hashimoto's disease), or neutral antibodies (355). Currently available bioassays are the thyroid-stimulating antibodies (TS-Ab) assays.…”

Section: A Clinical Presentation and Diagnosismentioning

confidence: 99%

Thyroid Function and Human Reproductive Health

Krassas¹,

2010

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Via its interaction in several pathways, normal thyroid function is important to maintain normal reproduction. In both genders, changes in SHBG and sex steroids are a consistent feature associated with hyper- and hypothyroidism and were already reported many years ago. Male reproduction is adversely affected by both thyrotoxicosis and hypothyroidism. Erectile abnormalities have been reported. Thyrotoxicosis induces abnormalities in sperm motility, whereas hypothyroidism is associated with abnormalities in sperm morphology; the latter normalize when euthyroidism is reached. In females, thyrotoxicosis and hypothyroidism can cause menstrual disturbances. Thyrotoxicosis is associated mainly with hypomenorrhea and polymenorrhea, whereas hypothyroidism is associated mainly with oligomenorrhea. Thyroid dysfunction has also been linked to reduced fertility. Controlled ovarian hyperstimulation leads to important increases in estradiol, which in turn may have an adverse effect on thyroid hormones and TSH. When autoimmune thyroid disease is present, the impact of controlled ovarian hyperstimulation may become more severe, depending on preexisting thyroid abnormalities. Autoimmune thyroid disease is present in 5-20% of unselected pregnant women. Isolated hypothyroxinemia has been described in approximately 2% of pregnancies, without serum TSH elevation and in the absence of thyroid autoantibodies. Overt hypothyroidism has been associated with increased rates of spontaneous abortion, premature delivery and/or low birth weight, fetal distress in labor, and perhaps gestation-induced hypertension and placental abruption. The links between such obstetrical complications and subclinical hypothyroidism are less evident. Thyrotoxicosis during pregnancy is due to Graves' disease and gestational transient thyrotoxicosis. All antithyroid drugs cross the placenta and may potentially affect fetal thyroid function.

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“…Various approaches to identify the TSHR epitopes have involved in silico, in vitro, in vivo , and clinical studies, and some TSHR epitope clusters were reported (7, 8). Thyroid function is regulated by not only TRAb but also cell-mediated immunity (9). Two major regulations (central and peripheral) maintain self-tolerance (2).…”

Section: Introductionmentioning

confidence: 99%

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

2016

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Graves’ disease (GD) is an organ-specific autoimmune disease, and thyrotropin (TSH) receptor (TSHR) is a major autoantigen in this condition. Since the extracellular domain of human TSHR (TSHR-ECD) is shed into the circulation, TSHR-ECD is a preferentially immunogenic portion of TSHR. Both genetic factors and environmental factors contribute to development of GD. Inheritance of human leukocyte antigen (HLA) genes, especially HLA-DR3, is associated with GD. TSHR-ECD protein is endocytosed into antigen-presenting cells (APCs), and processed to TSHR-ECD peptides. These peptide epitopes bind to HLA-class II molecules, and subsequently the complex of HLA-class II and TSHR-ECD epitope is presented to CD4+ T cells. The activated CD4+ T cells secrete cytokines/chemokines that stimulate B-cells to produce TSAb, and in turn hyperthyroidism occurs. Numerous studies have been done to identify T- and B-cell epitopes in TSHR-ECD, including (1) in silico, (2) in vitro, (3) in vivo, and (4) clinical experiments. Murine models of GD and HLA-transgenic mice have played a pivotal role in elucidating the immunological mechanisms. To date, linear or conformational epitopes of TSHR-ECD, as well as the molecular structure of the epitope-binding groove in HLA-DR, were reported to be related to the pathogenesis in GD. Dysfunction of central tolerance in the thymus, or in peripheral tolerance, such as regulatory T cells, could allow development of GD. Novel treatments using TSHR antagonists or mutated TSHR peptides have been reported to be effective. We review and update the role of immunogenic TSHR epitopes and HLA in GD, and offer perspectives on TSHR epitope specific treatments.

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Antithyrotropin Receptor Antibody: An Update

Cited by 27 publications

References 129 publications

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

Prognostic Value of Thyrotropin Receptor Antibodies (TRAb) in Graves' Disease: A 120 Months Prospective Study

Thyroid Function and Human Reproductive Health

Thyrotropin Receptor Epitope and Human Leukocyte Antigen in Graves’ Disease

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