Thyroid-associated ophthalmopathy (
TAO) is an orbital autoimmune disorder of the extraocular and eyelid muscles and surrounding connective and adipose tissue. Although mononuclear cell infiltration of orbital tissue is a characteristic feature of
TAO the likely role of T lymphocyte reactivity against eye muscle
antigens in the initiation of eye muscle damage in
TAO has not been explored in detail. Therefore, we tested for T lymphocyte sensitisation to three eye muscle
antigens namely,
calsequestrin, G2s and
flavoprotein (Fp), in patients with
Graves' ophthalmopathy (GO), Graves'
hyperthyroidism (GH) without ophthalmopathy and age and sex matched normal subjects. T lymphocyte reactivity was determined in a proliferation assay, results being expressed as stimulation index (SI). Mean ( +/- SE) SI for patients with GO, but not GH without ophthalmopathy, were significantly greater than that for normal subjects for
calsequestrin and Fp, but not G2s. Mean ( +/- SE) SI was also significantly increased in patients with active ophthalmopathy, but not chronic ophthalmopathy, compared to normal subjects, for
calsequestrin and Fp, but not G2s. Overall, positive lymphocyte proliferation to
calsequestrin was demonstrated in 59% of patients with GO and 33% of patients with GH, which was significantly greater than in normals for both groups. In conclusion, we have demonstrated significant T lymphocyte reactivity to
calsequestrin and, to a lesser extent, Fp in patients with GO. Because
calsequestrin is located in the cell membranes of the eye muscle cell during the myotubular stage of the cell cycle, its targeting might be the primary reaction which leads to extraocular muscle
inflammation in patients with GH.