Biological Activity of Autoantibodies From Patients With Thyroid-associated Ophthalmopathy: In Vitro Effects on Porcine Extraocular Myoblasts

To determine whether antibodies to orbital tissue have a pathogenicrole in thyroid-associated ophthalmopathy, the in vitroeffectsof IgG from patients with thyroid-associated ophthalmopathyon porcine extraocular myoblast growth were studied. Growthof primary extraocular myoblast cultures and extraocular myoblastclones was stimulated by patients' IgG, as measured by [³H]thymidineuptake and bromodeoxyuridine incorporation. Myoblasts respondedin a dose-related fashion to increasing concentrations of patients'IgG, and the response was reversed by anti-human IgG. The growthstimulating effect of patients' IgG was relatively specificto extraocular myoblasts, compared to skeletal myoblasts. IndividualIgG samples from 36 patients with ophthalmopathy gave rise tohigher growth responses of cloned extraocular myoblasts, thaneither 31 normal controls (p<0.005), or IgG from 10 patientswith Graves' disease without evidence of ophthalmopathy (p<0.001).Myoblast growth-stimulating antibody did not correlate withthyroid autoantibody levels (thyrotrophin receptor antibodyor thyroid microsomal antibody levels), but correlated significantlywith binding to extraocular muscle membranes (r=0.524, p<0.001).Eye-muscle stimulating antibodies were demonstrable in seraof patients with thyroid-associated ophthalmopathy, and maybe responsible for the enlargement of eye muscle in this disease.