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hypothyroidism [ 10 , 12 ]. TSHR Ab can be measured with either a bioassay or a binding assay. However, bioassays have the advantage of indicating not only the presence of Ab but also their functional activity and potency. Since no studies that compare the
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either via competitive-binding immunoassays or with bioassays [ 4 ]. Antibody-binding assays only report the presence or absence of TSHR-Ab and their concentrations, but do not indicate their functional activity. Bioassays, in contrast, indicate whether
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facilities and a lot of time [ 9 ], which limit their use outside specialized laboratories. In order to overcome these limitations, we established a new live-cell bioassay that uses a genetically engineered Chinese hamster ovary cell line expressing human
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present in the same patient [ 15 ]. A number of TSH-R-Ab immunoassays have been developed, but only bioassays for TSH-R-Ab, regardless of the readout used, are able to distinguish between the functional TSH-R-Ab activities [ 16 - 18 ]. The second
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and thyroid-related antibodies. Bioassay for Blocking TSHR Antibodies Levels of serum TSHR-blocking antibodies (TBAb) were measured according to the manufacturer’s (Quidel, San Diego, USA) instructions for the CE-marked cell-based bioassay [ 27
Division of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
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Division of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
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Division of Endocrinology and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
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Objectives: To verify the involvement of NKX2-1 gene in infants with brain-lung-thyroid (BLT) syndrome and hypothyroid phenotypes variable among congenital hypothyroidism (CH) or idiopathic mild hypothyroidism (IMH) of postnatal onset. Methods: The candidates were selected by a case-finding approach in 130 CH and 53 IMH infants. The NKX2-1 gene was analyzed by direct sequencing and multiplex ligation-dependent probe amplification. The variants were studied in vitro, by expression analyses and luciferase bioassay. Results: Four cases (3 CH and 1 IMH) consistent with BLT syndrome were identified. Two children were affected with respiratory distress and CH, but wild-type NKX2-1 gene. The remaining two presented choreic movements and no pulmonary involvement, but discrepant thyroid phenotypes: one had severe CH with lingual ectopy and the other one IMH with gland in situ. They were carriers of new de novo heterozygous frameshift mutations of NKX2-1 (c.177delG and c.153_166del14). The c.177delG leads to a prematurely truncated protein (p.H60TfsX11) with undetectable activity in vitro. The c.153_166del14 leads to the generation of an elongated aberrant protein (p.A52RfsX351) able to translocate into the nucleus, but completely inactive on a responsive promoter. Conclusions: Two novel heterozygous frameshift mutations of NKX2-1 were identified in 2 cases selected on the basis of a BLT-like phenotype among 183 hypothyroid infants. The atypical hypothyroid phenotypes of these 2 children (CH with lingual ectopy or IMH of postnatal onset) further expand the clinical spectrum that can be associated with NKX2-1 mutations.
Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
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Department of Ophthalmology, Salmaniya Medical Complex, Government Hospitals, Bahrain
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Department of Ophthalmology, Vicente Sotto Memorial Medical Center, Cebu City, Philippines
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Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China
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Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China
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Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
Hong Kong Eye Hospital, Hong Kong Special Administrative Region, China
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). Another assay is the functional thyroid-stimulating immunoglobulin (TSI) bioassay, which mainly detects the thyroid-stimulating antibody subtype. Despite TSI being more closely related to disease activity and severity than TBII, the clinical implications
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-R-Ab concentration measured with second- and third-generation binding assays were 97 and 98%, respectively [ 25 ]. In contrast, the highly sensitive cell-based bioassays [ 26 - 33 ] exclusively differentiate between the TSH-R-stimulating Ab (TSAb) and TSH
Institut National de la Recherche Médicale, UMR U895, Université Nice-Sophia Antipolis, Nice, France
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Institut National de la Recherche Médicale, UMR U895, Université Nice-Sophia Antipolis, Nice, France
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immunoradiometric assay (Thyroglobulin IRMA, Cisbio Bioassays, Bagnols-sur-Cèze, France). TBG was measured by RIA: RIA-gnost TBG (Cisbio Bioassays), as was rT3: RIA rT3 (Pasteur Cerba Laboratory). Reference ranges for FT4 and TSH were established in our laboratory
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were moderately elevated at 3.2 IU/L (reference range <1.75), and biological activity of TRAbs was assessed by bioassay. Severely high activity of TBAbs was observed (89%, reference range 0–10%), and no TSAbs were detected (reference range <140%). TRAbs
