Document Detail


A bioluminescence assay for thyrotropin receptor antibodies predicts serum thyroid hormone levels in patients with de novo Graves' disease.
MedLine Citation:
PMID:  16584516     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: TSH receptor antibodies (TBII) in Graves' disease (GD) may be TSH receptor stimulating (TSAb) and blocking (TBAb) antibodies. In commercially available assays however, only total TBII titres can be measured, without discriminating between TSAb and TBAb. OBJECTIVE: To design a TBII bioassay to detect of TSAb and to correlate TSAb activity with severity of hyperthyroidism in de novo GD patients. PATIENTS: Thirty-five patients with de novo GD and 27 controls. METHODS: The JP-26-26 cell line, which constitutively expresses the TSH receptor (TSHR), was stably transfected with a cyclic adenosine monophosphate responsive element--luciferase construct. The clone B1 exhibited a near linear increase in luminescence from 0.2 mU/l to 50 mU/l bovine TSH and was used as a TBII bioassay. TBII, free T4 and TSH were measured in the sera of all patients and controls. RESULTS: In the sera of 35 GD patients, TBII titres did not correlate with serum free T4 concentrations. In contrast, a strong and highly significant correlation was found between TSHR stimulating activity (luminescence) as measured with the TBII bioassay and serum free T4 levels (R = 0.80, P < 0.001). Interestingly, the luminescence/TBII ratio had a wide range at low TBII titres, whereas high TBII titres were associated with a low degree of TSHR activation. The TBII bioassay also detected TBAb in GD patients who spontaneously developed hypothyroidism. CONCLUSIONS: The B1-TBII-bioassay as developed in our laboratory has a high sensitivity for the detection of TSAb in GD and predicts the severity of hyperthyroidism in untreated GD patients. In addition, we found that high TBII titres are associated with weak TSHR activation.
Authors:
G C J Hovens; A M J Buiting; M Karperien; B E P B Ballieux; G van der Pluijm; A M Pereira; J A Romijn; J W A Smit
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinical endocrinology     Volume:  64     ISSN:  0300-0664     ISO Abbreviation:  Clin. Endocrinol. (Oxf)     Publication Date:  2006 Apr 
Date Detail:
Created Date:  2006-04-04     Completed Date:  2006-07-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0346653     Medline TA:  Clin Endocrinol (Oxf)     Country:  England    
Other Details:
Languages:  eng     Pagination:  429-35     Citation Subset:  IM    
Affiliation:
Department of Endocrinology, Leiden University Medical Center, Leiden, Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antibodies, Blocking / blood
Autoantibodies / blood*
Biological Assay / methods
Case-Control Studies
Cell Line
Female
Graves Disease / blood*
Humans
Immunoglobulins, Thyroid-Stimulating / blood
Luminescent Measurements
Male
Receptors, Thyrotropin / blood,  immunology*
Thyroid Hormones / blood*
Chemical
Reg. No./Substance:
0/Antibodies, Blocking; 0/Autoantibodies; 0/Immunoglobulins, Thyroid-Stimulating; 0/Receptors, Thyrotropin; 0/Thyroid Hormones; 0/thyrotropin-binding inhibitory immunoglobulin

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