Thyroid peroxidase autoantibodies of IgE class in thyroid autoimmunity

Recently, we converted a thyroid peroxidase (TPO)-specific human autoantibody Fab (SP1.4) into an IgE molecule (IgE-SP1.4) which permits antigen capture via Fc epsilon receptors on B cells and presentation to T cells. An important question which arose was whether IgE class TPO autoantibodies are present in vivo. By ELISA, TPO autoantibodies of IgG1 and IgG4 subclasses, but not IgE, were readily detectable in patients' sera. However, such negative data were not definitive because high concentrations of IgG class TPO autoantibodies could obscure the presence of much lower concentrations of IgE class autoantibodies. We, therefore, established a specific assay based on IgE "capture" to remove other isotypes before incubation with TPO. In an initial survey, 125I-TPO binding was higher in sera from 16 patients with autoimmune thyroid disease than in 6 controls (8.4 +/- 0.8% versus 0.7 +/- 0.2%; mean +/- SEM). Unlabeled TPO (10(-8) M) inhibited 125I-TPO binding by patients' (but not controls') IgE. Further, TPO binding by IgE-SP1.4 was unaffected by IgG class TPO autoantibodies. Titers of IgE class TPO autoantibodies were low, detectable at a 1/60 dilution in 4/5 sera studied. In a larger series, IgE class TPO autoantibodies were present in 13 of 18 Graves' and in 12 of 17 Hashimoto patients (sera diluted 1/6). Sera were considered to be positive with TPO binding greater than the mean + 3 SD of values for 23 control sera (1.8%). In conclusion, we provide the first evidence for TPO autoantibodies of IgE class in patients with autoimmune thyroid disease. Because of their low concentration, these autoantibodies are unlikely to play a role in antigen presentation in vivo. However, their presence strengthens the link between autoimmune thyroid disease and immune responses involving TH2 cells.