Hypothyroidism Induced by a TSH Receptor Peptide-Implications for Thyroid Autoimmunity

Area of Science:

• Immunology
• Endocrinology
• Pathology

Background:

• Neutral thyrotropin receptor autoantibodies (N-TSHR-Ab) targeting the TSHR ectodomain's hinge region can cause thyroid cell damage in vitro.
• Previous studies developed a monoclonal antibody (MC1) that induced thyroid stress and apoptosis in vivo.

Purpose of the Study:

• To investigate the effects of endogenously generated N-TSHR-Abs in vivo, mimicking autoimmune responses.
• To explore the mechanisms underlying TSHR-Ab-induced thyroid damage.

Main Methods:

• Balb/c mice were immunized with a TSHR hinge region peptide over 18 weeks.
• Serum analysis included TSHR antibodies, thyroglobulin (TG) and anti-TG levels, thyroxine, and TSH.
• Thyroid histology and spleen immune cell flow cytometry were performed.

Main Results:

• TSHR-peptide immunization led to the development of N-TSHR-Abs, causing thyroid follicular destruction and apoptosis.
• M1 macrophage infiltration, thyroglobulin release, and induction of anti-TG antibodies were observed.
• These changes resulted in hypothyroidism and elevated TSH levels.

Conclusions:

• Endogenous N-TSHR-Abs can induce thyroid cell damage through apoptosis and M1 macrophage infiltration.
• The study demonstrates a mechanism by which TSHR autoantibodies lead to hypothyroidism.