TSH Receptor Antibody Functionality and Nomenclature

Citation: Kahaly GJ and Diana T (2017) TSH Receptor Antibody Functionality and Nomenclature. This general commentary on the above, recently published New England Journal of Medicine review article wishes to clarify both the nomenclature as well as the role of autoantibodies (Ab) to the TSH receptor (TSH-R) pertaining to the serological diagnosis of Graves' disease (GD). Various terms have been used to describe the different types of TSH-R-Ab. It is important for the clinician to be aware of the different nomenclature as this will frequently reflect which assay is performed by the laboratory (Table 1). TSH-R-Ab, often referred to as TRAb, refers to any type of Ab interacting specifically with the TSH-R. Because these Ab are commonly assessed in a competitive binding assay, they are referred to as TSH-R-binding inhibitory immunoglobulins (TBII). By contrast, cell-based bioassays measure either TSH-R stimulatory antibodies (TSAb) or TSH-R-stimulating immunoglobulins, or alternately TSH-R-blocking antibodies (TBAb) or TSH-R-blocking immuno-globulins. Alternative terminologies for blocking antibodies are TSH-R-stimulating blocking Ab or TSH-R-blocking Ab (TRBAb). In this commentary, we will use TSH-R-Ab as a general term to refer to anti-TSH-R-Ab irrespective of the specific assay used. We will use TBII to refer to the Ab measured via binding assays, whereas Ab measured via bioassays will be referred to as TSAb for stimulatory and TBAb for blocking Ab. Graves' disease is caused by persistent, unregulated stimulation of thyroid cells by TSH-R-stimulating Ab (TSAb) that activate the TSH-R (1). TSAb, like TSH, bind primarily to the large amino terminal ectodomain of the TSH-R and activate the cAMP signal transduction pathway leading to stimulation of thyroid hormone production and proliferation of thyrocytes. Since the discovery of TSAb as the causative agent of GD, there have been numerous studies that have demonstrated the significance of the levels of these Ab during the course of the disease as well as during antithyroid drug treatment in both adults and children (2, 3). Other types of TSH-R antibodies can antagonize or block the action of TSH and in doing so cause hypothyroidism in certain patients with various types of autoimmune thyroiditis, particularly Hashimoto's thyroiditis. TSH-R antibodies that neither induce the cAMP signal pathway nor block the binding of TSH are referred to as neutral or recently " cleavage " Ab and currently are not known to have a functional effect (4). There is evidence, however, that neutral Ab may induce signaling pathways distinct from the cAMP …