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Clinical value of functional thyrotropin receptor antibodies in Serbian patients with Graves’ orbitopathy

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Abstract

Purpose

Thyrotropin receptor autoantibodies (TSH-R-Ab) are heterogeneous in their biological function and play a significant role in the pathophysiology of both Graves’ disease and Graves’ orbitopathy (GO). The clinical significance and utility of determining functional TSH-R-Ab in a Serbian collective were evaluated.

Methods

91 consecutive patients with GO were included in this study. Total TSH-R-Ab concentration, referred to as TSH-R binding inhibitory immunoglobulins (TBII) was detected using a competitive-binding immunoassay. Stimulating and blocking TSH-R-Ab (TSAb and TBAb) were measured with cell-based bioassays.

Results

Stimulating TSAb activity and TBII positivity were detected in 85 of 91 (93.4%) and 65 of 91 (71.4%) patients with GO (P < 0.001). Blocking TBAb activity was observed in only one patient who expressed dual stimulating and blocking TSH-R-Ab activity. The sensitivity rates for differentiating between clinically active versus inactive and mild versus moderate-to-severe GO were 100% and 100% for TSAb, respectively. In contrast, these were 82% and 87% only for TBII. Seven of eight (87.5%) and one of eight (12.5%) euthyroid patients with GO were TSAb and TBII positive, respectively (P < 0.031). TSAb serum levels significantly predicted GO activity compared to TBII (odds ratio, OR, 95%CI: 3.908, 95%CI 1.615–9.457, P = 0.003; versus 2.133, 0.904–5.032, P = 0.084, univariate analysis; and OR 4.341, 95%CI 1.609–11.707, P = 0.004; versus 2.337, 0.889–6.145, P = 0.085 multivariate analysis).

Conclusion

Stimulating TSAb are highly prevalent in patients with GO and show superior clinical characteristics and predictive potential compared to the traditionally used TBII.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Acknowledgements

This research was funded partially by a grant No. 175036 of the Ministry of Education, Science and Technological Development, Republic of Serbia, and through Grant Agreement with the University of Belgrade-Faculty of Pharmacy No: 451-03-9/2021-14/200161.

Funding

This research was funded partially by a grant No. 175036 of the Ministry of Education, Science and Technological Development, Republic of Serbia, and through Grant Agreement with the University of Belgrade-Faculty of Pharmacy No: 451-03-9/2021-14/200161.

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Author notes

  1. G.J. Kahaly and S. Ignjatović share senior authorship.

Authors and Affiliations

  1. Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

    M. Sarić Matutinović & S. Ignjatović

  2. Molecular Thyroid Research Laboratory, Department of Medicine I, Johannes Gutenberg University (JGU) Medical Center, Mainz, Germany

    T. Diana & G. J. Kahaly

  3. Clinic of Endocrinology, University Clinical Center of Serbia, Belgrade, Serbia

    B. Nedeljković Beleslin, J. Ćirić & M. Žarković

  4. Medical Faculty, University of Belgrade, Belgrade, Serbia

    B. Nedeljković Beleslin, J. Ćirić & M. Žarković

  5. Center for Medical Biochemistry, University Clinical Center of Serbia, Belgrade, Serbia

    S. Ignjatović

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  1. M. Sarić Matutinović
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Contributions

SMM: concept/design, material preparation, data collection, laboratory analysis, statistics, writing- original draft preparation; DT: laboratory analysis, interpretation, review and editing; NBB: concept/design, data collection and analysis, interpretation, critical review, approval of the article; ĆJ: data collection and analysis, critical revision; ŽM: design, critical review and editing; KJG: critical review and editing, final approval; IS: concept/design, critical review, final approval.

Corresponding author

Correspondence to M. Sarić Matutinović.

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Conflict of interest

The JGU Medical Center has received research-associated funding from Quidel, USA and Roche, Germany. GJK consults for Quidel. MSM, TD, BNB, JĆ, MŽ, and SI have no relevant financial or non-financial interests to disclose.

Ethics approval

All patients signed an informed consent and Ethics Committee approval of the Faculty of Pharmacy, University of Belgrade was obtained prior to the start of the study (17.06.2019/944/3).

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Research was conducted in accordance with the guidelines of good clinical and laboratory practice, the Declaration of Helsinki and applicable national regulations and institutional policies.

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Sarić Matutinović, M., Diana, T., Nedeljković Beleslin, B. et al. Clinical value of functional thyrotropin receptor antibodies in Serbian patients with Graves’ orbitopathy. J Endocrinol Invest 45, 189–197 (2022). https://doi.org/10.1007/s40618-021-01652-y

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