Does autoimmunity against thyroglobulin play a role in the pathogenesis of Graves’ ophthalmopathy: a review

Figures & data

Table 1 Evidence supporting a role of thyroglobulin in the pathogenesis of Graves’ ophthalmopathy

1. Thyroglobulin is a large and very antigenic protein and thecorresponding autoantibodies react with it in many clinical and experimental situations, so why not in the orbit?

2. Intact thyroglobulin can be detected in the orbits of patients with Graves’ ophthalmopathy so would be seen by circulating thyroglobulin antibodies

3. In patients with Graves’ hyperthyroidism, serum thyroglobulin levels correlate with the prevalence and severity of any associated ophthalmopathy

4. In patients with Graves’ ophthalmopathy, serum thyroglobulin levels correlate with serum titers of TSHr antibodies

5. In patients with Graves’ ophthalmopathy, serum thyroglobulin levels correlate with TSHr antibody titers, suggesting that both thyroid antigens are released at the same time

6. Thyroglobulin antibodies in the circulation and from the thyroid would bind to Tg in the orbit, although this has not been demonstrated

Abbreviation: TSHr, TSH receptor.

Table 2 Proposed pathogenic mechanisms of Tg for Graves’ ophthalmopathy

1. Thyroglobulin antibodies bind to native thyroglobulin which is attached to the orbital fibroblasts. Subsequently the production of thyroglobulin/anti-thyroglobulin immune complexes stimulate the fibroblast, contributing to the orbital inflammation.

2. CD8^+ cytotoxic T lymphocytes directed against the extra ocular muscle fiber are also likely to be involved, but specific targets and effects of the reactions are not understood

Figure 1 Hypothetical role of thyroglobulin in Graves’ ophthalmopathy.