Endocrine Abstracts

Type 2 5’-deiodinase (DIO2) is a common enzyme between thyroid and eye muscle tissues involving in T₄ conversion to T₃. The role of DIO2 has been demonstrated in the development of skeletal muscle. Increased DIO2 activities was connected to eye muscle enlargements in hyperthyroid Graves’ ophthalmopathy. In this study, the presence of antibodies against human eye muscle tissue fractions with the binding to DIO2 peptide was investigated and measured their inhibiting effects on lymphocyte mitogen-activated protein kinase (MAPK) activation.

Antibodies against DIO2 peptide (aa 123–143) and human eye muscle membrane (EyeM) and cytosol (EyeC) fractions were measured in 74 patients with Graves’ disease and 32 controls using ELISA assay. Thyroid hormones and antibiodies against thyroid peroxidase and thyroglobulin were detected by chemilimunescence assay. TSH receptor antibodies and MAPK activation were measured by radio-immune assays.

Hyperthyroid Graves’ patients without ophthalmopathy (n=30) showed more frequent binding to DIO2 peptide than patients with ophthalmopathy (n=23): 5 cases (37.5%) vs none for anti-EyeM IgG out of 8; 6 cases (20%) vs none for anti-EyeC IgG out of 30; P<0.02; 3 cases (25%) vs none for anti-EyeC IgM out of 12. Correlation was demonstrated between anti-EyeM IgG (P<0.01, r=0.3507) or anti-EyeC IgM (P<0.02, r=0.3178) and anti-DIO2 peptide antibodies. In hyperthyroidism, anti-DIO2 peptide antibodies correlated positively with TSH (P<0.01, r=0.3498) and inversely with FT₄ (P<0.05, r=−0.2757) levels. Hyper-thyroid Graves’ patient sera with cross reactivity to DIO2 peptide inhibited lymphocyte MAPK activations after 0 and 120 minutes compared with those using control sera.

The results highlighted a cross reactivity between anti-EyeM or –EyeC and anti-DIO2 peptide antibodies. Anti-DIO2 peptide antibodies demonstrated inverse correlation with FT₄ levels and inhibited lymphocyte MAPK activations. Therefore, anti-DIO2 peptide antibodies may be responsible for lower FT₄ levels via decreased MAPK activation highlighting their protective roles against the development of ophthalmopathy.