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Accuracy of receptor-based methods for detection of thyrotropin-receptor autoantibodies: a new automated third-generation immunoassay shows higher analytical and clinical sensitivity for the differential diagnosis of hyperthyroidism
Autoimmunity Highlights volume 1, pages95–100(2010)
Abstract
Purpose
Specific autoantibodies acting as TSH receptor agonists (TRAb) are responsible for Graves’ disease (GD). In the last 30 years three generations of assay methods for the detection of TRAb have become available. The aim of this multicentre study was to evaluate the analytical sensitivity, precision and diagnostic accuracy of TRAb measurement using a new automated assay in comparison with a second-generation standard method.
Methods
Serum samples from patients with GD (n=82), autoimmune thyroiditis (AIT, n=57) or hyperthyroidism (HT, n=292), from 106 healthy subjects and from 57 patients with infectious diseases were analysed using a third-generation TRAb immunoassay (anti-TSHR, RAD 120; Radim, Italy) based on the human monoclonal TSH receptor antibody M22.
Results
Using a cut-off value of 1.25 mIU/l, established by ROC curve analysis, 80/82 GD patients (97.5%), 68/292 HT patients (23.2%), and 6/57 AIT patients (10.5%) were TRAb-positive with the M22-based automated assay. The percentages of TRAb positivity were lower in the same patients when the measurements were done with the second-generation method (95.1%, 18.9%, 7.0%, respectively).
Conclusion
The M22-based automated immunoassay shows high functional sensitivity (0.4 mIU/l) and high diagnostic specificity, is more sensitive than the standard second-generation method and is less time-consuming and labourintensive, and is therefore the up-to-date technology for TRAb detection in clinical practice.
References
- 1.
Rees Smith B, Sanders J, Furmaniak J (2007) TSH receptor antibodies. Thyroid 17:923–938
- 2.
Schott M, Scherbaum WA, Morgenthaler NG (2005) Thyrotropin receptor autoantibodies in Graves’ disease. Trends Endocrinol Metab 16:243–248
- 3.
Adams DD, Purves HD (1956) Abnormal responses in the assay of thyrotropin. Proc Univ Otago Med Sch 34:11–12
- 4.
Meek JC, Jones AE, Lewis UI, Vanderlaan WP (1964) Characterization of the long-acting thyroid stimulator of Graves’ disease. Proc Natl Acad Sci U S A 52:342–349
- 5.
McKenzie JM (1958) The bioassay of thyrotropin in serum. Endocrinology 63:372–382
- 6.
Manley SW, Bourke JR, Hawker RW (1974) The thyrotropinreceptor in guinea-pig thyroid homogenate: interaction with the long-acting thyroid stimulator. J Endocrinol 61:437–445
- 7.
Rees Smith B, Hall R (1974) Thyroid-stimulating immunoglobulins in Graves’ disease. Lancet 2:427–431
- 8.
Rees Smith B, Hall R (1981) Measurement of thyrotropin receptor antibodies. Methods Enzymol 74:405–421
- 9.
Shewring G, Rees Smith B (1982) An improved radioreceptor assay for TSH receptor antibodies. Clin Endocrinol (Oxf) 17:409–414
- 10.
Southgate K, Kreagh F, Teece M et al (1984) A receptor assay for the measurement of TSH receptor antibodies in unextracted serum. Clin Endocrinol (Oxf) 20:539–548
- 11.
Gupta MK (2000) Thyrotropin-receptor antibodies in thyroid diseases: advances in detection techniques and clinical applications. Clin Chim Acta 293:1–29
- 12.
Illicki A, Gamstedt A, Karlsson FA (1992) Hyperthyroid Graves’ disease without detectable thyrotropin receptor antibodies. J Clin Endocrinol Metab 74:1090–1094
- 13.
Mukuta T, Tamai H, Oshima A et al (1994) Immunological findings and thyroid function of untreated Graves’ disease patients with undetectable TSH-binding inhibitor immunoglobulin. Clin Endocrinol (Oxf) 40:215–219
- 14.
Kawai K, Tamai H, Matsubayashi S et al (1995) A study of untreated Graves’ patients with undetectable TSH binding inhibitor immunoglobulins and the effect of antithyroid drugs. Clin Endocrinol 43:551–556
- 15.
Costagliola S, Morgenthaler NG, Hoermann R et al (1999) Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Gravess’ disease. J Clin Endocrinol Metab 84:90–97
- 16.
Bolton J, Sanders J, Oda Y et al (1999) Measurement of thyroid-stimulating hormone receptor autoantibodies by ELISA. Clin Chem 45:2285–2287
- 17.
Schott M, Feldkamp J, Bathan C et al (2000) Detecting TSH receptor antibodies with the recombinant TBII assay. Technical and clinical evaluation. Horm Metab Res 32:429–435
- 18.
Bülow Pedersen I, Knudsen N, Perrild H et al (2001) TSH receptor antibody measurement for differentiation of hyperthyroidism into Graves’ disease and multinodular toxic goiter: a comparison of two competitive binding assays. Clin Endocrinol 55:381–390
- 19.
Giovanella L, Ceriani L, Garancini S (2001) Evaluation of 2nd generation radioreceptional assay for anti-TSH receptor antibodies (TRAb) in autoimmune thyroid diseases. Comparison with 1st generation anti-thyroperoxidase antibodies (AbTPO). Q J Nucl Med 45:115–119
- 20.
Morgenthaler NG, Nagata A, Katayama S et al (2002) Detection of low titre TBII in patients with Graves’ disease using recombinant human TSH receptor. Clin Endocrinol 57:193–198
- 21.
Kamijo K (2003) TSH receptor antibody measurement in patients with various thyrotoxicosis and Hashimoto’s thyroiditis: a comparison of two two-step assays, coated plate ELISA using porcine TSH-receptor and coated tube radioassay using recombinant TSH-receptor. Endocr J 50:113–116
- 22.
Massart C, Orgiazzi J, Maugendre D (2001) Clinical validity of a new commercial method for detection of TSH receptor binding antibodies in sera of patients with Graves’ disease treated with antithyroid drugs. Clin Chim Acta 304:39–47
- 23.
Villalta D, Orunesu E, Tozzoli R et al (2004) Analytical and diagnostic accuracy of “second generation” assays for thyrotropin receptor antibodies with radioactive and chemiluminescent tracers. J Clin Pathol 57:378–382
- 24.
Kamijo K, Ishikawa K, Tanaka M (2005) Clinical evaluation of 3rd generation assay for thyrotropin receptor antibodies: the M22-biotin-based ELISA initiated by Smith. Endocr J 52:525–529
- 25.
Yoshimura Noh J, Miyazaki N, Ito K et al (2008) Evaluation of a new rapid and fully automated electroluminescence immunoassay for thyrotropin receptor autoantibodies. Thyroid 18:1157–1164
- 26.
Liu C, Hermsen D, Domberg J et al (2008) Comparison of M22-based ELISA and human TSH receptor-based luminescence assay for the measurement of thyrotropin receptor antibodies in patients with thyroid diseases. Horm Metab Res 40:479–483
- 27.
Zöphel K, Grüning T, Roggenbuck D et al (2008) On specificity of 2nd generation TSH receptor autoantibody measurements. Clin Lab 54:243–249
- 28.
Massart C, Sapin R, Gibassier J et al (1999) Intermethod variability in TSH receptor antibody measurement: implication for the diagnosis of Graves disease and for follow-up of Graves ophthalmopathy. Clin Chem 55:183–186
- 29.
Bülow Pedersen I, Handberg A, Knudsen N et al (2010) Assays for thyroid-stimulating hormone receptor antibodies employing different specific ligands and ligand partners may have similar sensitivity and specificity but are not interchangeable. Thyroid 10:127–133
- 30.
Zöphel K, Roggenbuck D, von Landerberg P et al (2010) TSH receptor antibody (TRAb) assays based on the human monoclonal autoantibody M22 are more sensitive than bovine TSH based assays. Horm Metab Res 42:65–69
- 31.
Rees Smith B, Bolton J, Young S et al (2004) A new assay for thyrotropin receptor autoantibodies. Thyroid 14:830–835
- 32.
Sanders J, Jeffreys J, Depretaere H et al (2004) Characteristics of a human monoclonal autoantibody to the thyrotropin receptor: sequence, structure and function. Thyroid 14:560–570
- 33.
Gassner D, Golla R, Stock W et al (2007) Development of a new automated assay for thyrotropin receptor autoantibodies on the Elecsys system. Clin Chem 53(suppl):A145
- 34.
Schott M, Hermsen D, Broecker-Preuss M et al (2008) Clinical value of the first automated TSH receptor autoantibody assay for the diagnosis of Graves’ disease: an international multicentre trial. Clin Endocrinol (Oxf) 71:566–573
- 35.
Hermsen D, Broecker-Preuss M, Casati M et al (2009) Technical evaluation of the first fully automated assay for the detection of TSH receptor autoantibodies. Clin Chim Acta 401:84–89
- 36.
Zweig MH, Campbell G (1993) Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clin Chem 39:561–577
- 37.
Zimmermann-Belsing T, Nygaard B, Rasmussen AK, Feldt-Rasmussen U (2002) Use of the second generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves’ disease. Eur J Endocrinol 146:173–177
- 38.
Morshed SA, Latif R, Davies TF (2009) Characterization of thyrotropin receptor antibody-induced signaling cascades. Endocrinology 150:519–529
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Tozzoli, R., Kodermaz, G., Villalta, D. et al. Accuracy of receptor-based methods for detection of thyrotropin-receptor autoantibodies: a new automated third-generation immunoassay shows higher analytical and clinical sensitivity for the differential diagnosis of hyperthyroidism. Autoimmun Highlights 1, 95–100 (2010). https://doi.org/10.1007/s13317-010-0014-4
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Keywords
- TSHR antibodies
- Automated TRAb immunoassay
- Graves’ disease
- Hyperthyroidism
- Sensitivity
- Specificity