Cell mediated immunity against three eye muscle antigens and correlation with eye signs in patients with transient and chronic thyroiditis

Background: Mild eye signs, especially itchiness and grittiness of the eyelids and upper eyelid retraction (UER), are found in about 25% of patients with Hashimoto's thyroiditis (HT) in whom antibodies against calsequestrin and flavoprotein (Fp) are often detected. The role of T lymphocyte reactivity against eye muscle antigens in patients with thyroiditis has not been investigated. Methods: We studied peripheral blood T lymphocyte reactivity against calsequestrin, Flavoprotein (Fp) and G2s in patients with transient (sub acute and silent) thyroiditis (TT) and HT, determined in a standard proliferation assay. Reactivity was expressed as stimulation index (SI) and correlated with signs of ophthalmopathy and upper eyelid disease, assessed as; NOSPECS classes, clinical activity score (CAS) and upper eyelid retraction (UER). Results: Positive lymphocyte proliferation to calsequestrin was demonstrated in 71% of TT patients all of whom had mild ophthalmopathy and this was significantly increased compared to normal control subjects. The prevalences of positive T cell reactivity to calsequestrin was also significantly increased in HT patients (38%) compared to the controls, all of whom had upper eyelid disease. Three out of 7 patients with upper eyelid disease (6 of the patients with TT or HT and one other patient with Graves' disease) taken as a separate group, demonstrated significant T lymphocyte sensitisation to calsequestrin. TSH-receptor antibodies were detected in only one TT patient and one patient with upper eyelid disease. Interpretation: The development of ophthalmopathy and/or eyelid retraction (in the absence of TSH-r antibodies and Graves' hyperthyroidism) in TT patients is closely associated with an autoimmune reaction against calsequestrin. These findings support the notion that ophthalmopathy and upper eyelid inflammation and dysfunction are independent autoimmune disorders not necessarily linked with thyroid autoimmunity and that T cell reactivity plays a role.