Antibodies against thyroid‑stimulating hormone receptor cause maternal‑neonatal transmission of Graves' Disease

Yu,Yue; Liu,Qian-Qi; Liu,De-Yun; Wang,Dan-Dan; Yang,Li-Qi; Ye,Shu-Ming

doi:10.3892/etm.2021.10688

Antibodies against thyroid‑stimulating hormone receptor cause maternal‑neonatal transmission of Graves' Disease

Authors:
- Yue Yu
- Qian-Qi Liu
- De-Yun Liu
- Dan-Dan Wang
- Li-Qi Yang
- Shu-Ming Ye
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Affiliations: Department of Pediatrics, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China, Department of Orthopedic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
Published online on: September 3, 2021 https://doi.org/10.3892/etm.2021.10688
Article Number: 1253
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate whether the thyroid‑stimulating hormone receptor (TSHR) autoantibodies (Ab) from mothers with Graves' disease (GD) could cause neonatal thyroid disease and the underlying mechanisms of this. An adenovirus expressing the TSHR A‑subunit and a control adenovirus expressing β‑galactosidase was constructed by Beijing Sino Geno Max Co., Ltd. The sequences were subsequently verified and amplified via PCR. A GD model was established in female BALB/c mice (n=90) by three intramuscular injections of a TSHR‑expressing adenovirus (Ad‑TSHR). Mice injected with Ad‑β‑galactosidase served as a sham immunization group. The immunized females were paired with unimmunized males to generate offspring. The serum levels of TSHR‑Ab and thyroxine (T4) of mothers and neonates were measured after delivery. Breast milk was collected from the stomachs of neonatal mice to determine the TSHR‑Ab levels. The positive rate of serum TSHR‑Ab (>0.3 IU/l) in the TSHR group was 99% (89/90) and 0% in the sham group. The mother mice in the TSHR group had elevated serum T4 levels and the thyroid pathological features of Graves' hyperthyroidism.GD mice gave birth to smaller newborns with thyroid pathological changes and higher serum levels of TSHR‑Ab and T4, compared to the offspring in the sham group. The TSHR‑Ab levels in breast milk from the GD mice declined with time. Mice immunized with Ad‑TSHR exhibited the clinicopathological features of human GD and give birth to neonates with thyroid disease at birth.

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