OSETLJIVOST TRI TESTA ZA ODREĐIVANJE ANTITELA NA RECEPTOR ZA TIREOSTIMULIŠUĆI HORMON U ORBITOPATIJI POVEZANOJ SA TIROIDNOM ŽLEZDOM
Osetljivost TSH-R-At testova u TAO
Ključne reči:
orbitopatija povezana sa tiroidnom žlezdom, antitela na receptor za tireostimulišući hormon, bioesej, ''sendvič imunohemijski test, ECLIA kompetitivni imunohemijski test
Sažetak
Uvod i ciljevi: Autoantitela na receptore tireostimulišućeg hormona (TSH-R-At) su nezamenljivi biomarkeri u laboratorijskoj proceni orbitopatije povezane sa tiroidnom žlezdom (TAO). U studiji je procenjena klinička osetljivost tri različita testa za određivanje TSH-R-At kod pacijenata sa TAO. Metode: U studiju je uključeno 87 uzastopnih pacijenata sa TAO i njihovi uzorci seruma su analizirani paralelno, upotrebom sva tri testa. Za merenje ukupne i vezujuće koncentracije TSH-R-At korišćeni su ECLIA imunohemijski test kompetitivnog vezivanja i ''sendvič'' hemiluminiscentni imunotest, dok je njihova funkcionalna aktivnost određena primenom metode stimulatornog ćelijskog biološkog testa, odnosno bioeseja (TSAb). Rezultati: U poređenju sa dva vezujuća imunotesta (ECLIA p<0,001, most p=0,003), biološki TSAb test je bio značajno osetljiviji za pozitivnu detekciju TSH-R-At kod pacijenata sa TAO. Nije primećena razlika (p=0,057) između ECLIA i ''sendvič'' vezujućeg imunotesta u pogledu stope osetljivosti. Svi pacijenti sa aktivnom i/ili umerenom do teškom TAO bili su pozitivni u TSAb biološkom testu (100% i 100%, redom), dok su stope pozitivnosti za ''sendvič'' imunotest i ECLIA vezujući imunohemijski test bile 89,7% i 82,1% za aktivnu TAO, i 90,2% i 86,3% za tešku TAO, redom. Negativne prediktivne vrednosti bioeseja, ''sendvič'' imunotesta i ECLIA imunotesta kompetitivnog vezivanja bile su 100%, 75% i 71%, redom za aktivnu TAO, odnosno 100%, 86% i 71%, redom za umerenu do tešku TAO. Superiornost biološke analize bila je najistaknutija kod eutireoidnog oblika (ET) TAO. Stope pozitivnosti TSAb bioeseja, ''sendvič'' i ECLIA imunotestova vezivanja bile su 89,6%, 75% i 64,6%, redom za neaktivnu TAO; 86,1%, 69,4% i 52,8% za blagu formu TAO; 87,5%, 62,5% i 12,5% za eutireoidni oblik TAO. ''Sendvič'' imunotest je bolje korelirao sa ECLIA testom vezivanja (ρ=0,893, p<0,001), u poređenju sa bioesejom (ρ=0,669, p<0,001). Zaključci: Kod pacijenata sa TAO različite aktivnosti i težine, TSAb biološki test pokazuje superiorne kliničke karakteristike u poređenju sa oba imunohemijska testa vezivanja.
Reference
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30. Nakatake N, Sanders J, Richards T, Burne P, Barrett C, Pra CD, et al. Estimation of serum TSH receptor autoantibody concentration and affinity. Thyroid 2006; 16: 1077–84.
31. Tahara K, Ishikawa N, Yamamoto K, Hirai A, Ito K, Tamura Y, Yoshida S, Saito Y, Kohn LD. Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor. Thyroid 1997; 7: 867–77.
32. Davies TF, Ando T, Lin RY, Tomer Y, Latif R. Thyrotropin receptor-associated diseases: from adenomata to Graves’ disease. J Clin Invest 2005; 115: 1972–83.
33. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid 2013; 23: 14–24.
34. Allelein S, Diana T, Ehlers M, Kanitz M, Hermsen D, Schott M, Kahaly GJ. Comparison of a bridge immunoassay with two bioassays for thyrotropin receptor antibody detection and differentiation. Horm Metab Res 2019; 51: 341–46.
35. Morshed SA, Ando T, Latif R, Davies TF. Neutral antibodies to the TSH receptor are present in Graves’ disease and regulate selective signaling cascades. Endocrinology 2010; 151: 5537–49.
36. Li Y, Kim J, Diana T et al. A novel bioassay for anti-thyrotrophin receptor autoantibodies detects both thyroid-blocking and stimulating activity. Clin Exp Immunol 2013; 173: 390–397
37. Diana T, Olivo PD, Kahaly GJ. Thyrotropin receptor blocking antibodies. Horm Metab Res 2018; 50: 853–62.
38. Diana T, Wuster C, Olivo PD et al. Performance and specificity of 6 immunoassays for tsh receptor antibodies: A multicenter study. Eur Thyroid J 2017; 6: 243–249.
39. Diana T, Wuster C, Kanitz M et al. Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies. J Endocrinol Invest 2016; 39: 1159–1165.
40. Diana T, Holthoff HP, Fassbender J, Wüster C, Kanitz M, Kahaly GJ, Ungerer M. A novel long-term Graves' disease animal model confirmed by functional thyrotropin receptor antibodies. Eur Thyroid J 2020;9(Suppl 1): 51–58.
41. McKee A, Peyerl F. TSI assay utilization: impact on costs of Graves' hyperthyroidism diagnosis. Am J Manag Care 2012; 18: e1–14.
42. Kahaly GJ, Diana T, Kanitz M, Frommer L, Olivo PD. Prospective trial of functional thyrotropin receptor antibodies in Graves disease. J Clin Endocrinol Metab 2020; 105: e1006–14.
43. Stöhr M, Oeverhaus M, Lytton SD, Horstmann M, Zwanziger D, Möller L, et al. Predicting the relapse of hyperthyroidism in treated Graves’ disease with orbitopathy by serial measurements of TSH-receptor autoantibodies. Horm Metab Res 2021; 53: 235–44.
44. Eckstein AK, Plicht M, Lax H, Neuhäuser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves' ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006 ; 91: 3464–70.
2. Bahn RS. Graves’ ophtalmopathy. N Engl J Med 2010; 362: 726–38.
3. Kahaly GJ, Diana T, Olivo PD. TSH receptor antibodies: relevance and utility. Endocr Pract 2020; 26: 97–106.
4. George A, Diana T, Langericht J, Kahaly GJ. Stimulatory thyrotropin receptor antibodies are a biomarker for Graves’ orbitopathy. Front Endocrinol (Lausanne) 2021; 11: 629925.
5. Kahaly GJ, Diana T, Glang J, Kanitz M, Pitz S, König J. Thyroid stimulating antibodies are highly prevalent in hashimoto’s thyroiditis and associated orbitopathy. J Clin Endocrinol Metab 2016; 101: 1998–2004.
6. Ponto KA, Diana T, Binder H, Matheis N, Pitz S, Pfeiffer N, Kahaly GJ. Thyroid-stimulating immunoglobulins indicate the onset of dysthyroid optic neuropathy. J Endocrinol Invest 2015; 38: 769–77.
7. Kahaly GJ, Diana T, TSH Receptor antibody functionality and nomenclature. Front Endocrinol (Lausanne) 2017; 8: 28.
8. Kahaly GJ. Management of Graves’ thyroidal and extrathyroidal disease: an update. J Clin Endocrinol Metab 2020; 105: 3704–20.
9. Gassner D, Stock W, Golla R, Roth HJ. First automated assay for thyrotropin receptor autoantibodies. Clin Chem Lab Med 2009; 47 :1091–95.
10. Tozzoli R, Bagnasco M, Giavarina D, Bizzaro N. TSH receptor autoantibody immunoassay in patients with graves' disease: improvement of diagnostic accuracy over different generations of methods. systematic review and meta-analysis Autoimmun Rev 2012; 12: 107–13.
11. Lytton SD, Kahaly GJ. Bioassays for TSH-receptor autoantibodies: an update. Autoimmun Rev 2010; 10: 116–22.
12. https://www.siemens-healthineers.com/ba/clinical-specialities/thyroid/tsi-assay
13. Frank CU, Braeth S, Dietrich JW, Wanjura D, Loos U. Bridge Technology with TSH receptor chimera for sensitive direct detection of TSH receptor antibodies causing Graves' disease: analytical and clinical evaluation. Horm Metab Res 2015; 47: 880–8.
14. Lytton SD, Schluter A, Banga PJ. Functional diagnostics for thyrotropin hormone receptor autoantibodies: bioassays prevail over binding assays. Front Biosci (Landmark Ed) 2018; 23: 2028–43.
15. Bossuyt PM, Irwig L, Craig J, Glasziou P. Comparative accuracy: assessing new tests against existing diagnostic pathways. BMJ 2006 ;332: 1089–92.
16. Hayen A , Macaskill P, Irwig L, Bossuyt P. Appropriate statistical methods are required to assess diagnostic tests for replacement, add-on, and triage. J Clin Epidemiol 2010; 63: 883–91.
17. Bartalena L, Kahaly GJ, Baldeschi L, Dayan CM, Eckstein A, Marcocci C. The 2021 European Group on Graves' orbitopathy (EUGOGO) clinical practice guidelines for the medical management of Graves' orbitopathy, Eur J Endocrinol. 2021 Aug 27;185(4):G43-G67.
18. Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European thyroid association guideline for the management of Graves’ hyperthyroidism. Eur Thyroid J 2018; 7: 167–86.
19. Nedeljkovic Beleslin B, Ciric J, Stojkovic M, Savic S, Lalic T, Stojanovic M, Miletic M, Knezevic M, Stankovic B, Zarkovic M. Comparison of efficacy and safety of parenteral versus parenteral and oral glucocorticoid therapy in Graves’ orbitopathy. International Journal of Clinical Practice 2020; 74: e13608
20. Mourits MP, Prummel MF, Wiersinga WM, Koornneef L. Clinical activity score as a guide in the management of patients with Grave’s ophthalmopathy. Clin Endocrinol (Oxf) 1997; 47: 9–14.
21. Lytton SD, Li Y, Olivo PD, Kohn LD, Kahaly GJ. Novel chimeric thyroid-stimulating hormone-receptor bioassay for thyroid-stimulating immunoglobulins. Clin Exp Immunol 2010; 162: 438–46.
22. Diana T, Li Y, Olivo PD, Lackner KJ, Kim H, Kanitz M, Kahaly GJ. Analytical performance and validation of a bioassay for thyroid-blocking antibodies. Thyroid 2016; 26: 734–40.
23. Bartalena L, Piantanida E, Gallo D, Lai A, Tanda ML. Epidemiology, natural history, risk factors, and prevention of Graves’ orbitopathy. Front Endocrinol (Lausanne) 2020; 11: 615993.
24. Bossuyt PM, Reitsma JB, Linnet K, Moons KGM. Beyond diagnostic accuracy: the clinical utility of diagnostic tests. Clinical Chemistry 2012; 58: 1636–43.
25. Linnet K, Bossuyt PM, Moons KG, Reitsma JB. Quantifying the accuracy of a diagnostic test or marker. Clin Chem 2012; 58: 1292–301.
26. Marino M, Ionni I, Lanzolla G, Sframeli A, Latrofa F, Rocchi R, Marcocci C. Orbital diseases mimicking graves’ orbitopathy: a long-standing challenge in differential diagnosis. J Endocrinol Invest 2020; 43: 401–11.
27. Sarić Matutinović M, Diana T, Nedeljković Beleslin B, Ćirić J, Žarković M, Kahaly GJ, Ignjatović S. Clinical value of functional thyrotropin receptor antibodies in Serbian patients with Graves' orbitopathy. J Endocrinol Invest 2021; 29.
28. Kahaly GJ, Wüster C, Olivo PD, Diana T. High titers of thyrotropin receptor antibodies are associated with orbitopathy in patients with Graves’ disease. J Clin Endocrinol Metab 2019; 104: 2561–68.
29. Kotwal A, Stan M. Thyrotropin receptor antibodies-an overview. Ophthalmic Plast Reconstr Surg 2018; 34: Suppl 4S: 20–7.
30. Nakatake N, Sanders J, Richards T, Burne P, Barrett C, Pra CD, et al. Estimation of serum TSH receptor autoantibody concentration and affinity. Thyroid 2006; 16: 1077–84.
31. Tahara K, Ishikawa N, Yamamoto K, Hirai A, Ito K, Tamura Y, Yoshida S, Saito Y, Kohn LD. Epitopes for thyroid stimulating and blocking autoantibodies on the extracellular domain of the human thyrotropin receptor. Thyroid 1997; 7: 867–77.
32. Davies TF, Ando T, Lin RY, Tomer Y, Latif R. Thyrotropin receptor-associated diseases: from adenomata to Graves’ disease. J Clin Invest 2005; 115: 1972–83.
33. McLachlan SM, Rapoport B. Thyrotropin-blocking autoantibodies and thyroid-stimulating autoantibodies: potential mechanisms involved in the pendulum swinging from hypothyroidism to hyperthyroidism or vice versa. Thyroid 2013; 23: 14–24.
34. Allelein S, Diana T, Ehlers M, Kanitz M, Hermsen D, Schott M, Kahaly GJ. Comparison of a bridge immunoassay with two bioassays for thyrotropin receptor antibody detection and differentiation. Horm Metab Res 2019; 51: 341–46.
35. Morshed SA, Ando T, Latif R, Davies TF. Neutral antibodies to the TSH receptor are present in Graves’ disease and regulate selective signaling cascades. Endocrinology 2010; 151: 5537–49.
36. Li Y, Kim J, Diana T et al. A novel bioassay for anti-thyrotrophin receptor autoantibodies detects both thyroid-blocking and stimulating activity. Clin Exp Immunol 2013; 173: 390–397
37. Diana T, Olivo PD, Kahaly GJ. Thyrotropin receptor blocking antibodies. Horm Metab Res 2018; 50: 853–62.
38. Diana T, Wuster C, Olivo PD et al. Performance and specificity of 6 immunoassays for tsh receptor antibodies: A multicenter study. Eur Thyroid J 2017; 6: 243–249.
39. Diana T, Wuster C, Kanitz M et al. Highly variable sensitivity of five binding and two bio-assays for TSH-receptor antibodies. J Endocrinol Invest 2016; 39: 1159–1165.
40. Diana T, Holthoff HP, Fassbender J, Wüster C, Kanitz M, Kahaly GJ, Ungerer M. A novel long-term Graves' disease animal model confirmed by functional thyrotropin receptor antibodies. Eur Thyroid J 2020;9(Suppl 1): 51–58.
41. McKee A, Peyerl F. TSI assay utilization: impact on costs of Graves' hyperthyroidism diagnosis. Am J Manag Care 2012; 18: e1–14.
42. Kahaly GJ, Diana T, Kanitz M, Frommer L, Olivo PD. Prospective trial of functional thyrotropin receptor antibodies in Graves disease. J Clin Endocrinol Metab 2020; 105: e1006–14.
43. Stöhr M, Oeverhaus M, Lytton SD, Horstmann M, Zwanziger D, Möller L, et al. Predicting the relapse of hyperthyroidism in treated Graves’ disease with orbitopathy by serial measurements of TSH-receptor autoantibodies. Horm Metab Res 2021; 53: 235–44.
44. Eckstein AK, Plicht M, Lax H, Neuhäuser M, Mann K, Lederbogen S, et al. Thyrotropin receptor autoantibodies are independent risk factors for Graves' ophthalmopathy and help to predict severity and outcome of the disease. J Clin Endocrinol Metab. 2006 ; 91: 3464–70.
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2021/12/06
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Original paper
Sva prava zadržana (c) 2021 Marija Sarić Matutinović, Tania Diana, Biljana Nedeljković Beleslin, Jasmina Ćirić, Miloš Žarković, Iva Perović Blagojević, George J. Kahaly, Svetlana Ignjatović
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