Differential autoantibody responses to thyroid peroxidase in patients with Graves' disease and Hashimoto's...

In order to examine the specificity of the autoantibody response to thyroid peroxidase (TPO, previously identified as thyroid microsomal antigen) in autoimmune thyroid disease, we examined reactivity of sera from 45 Hashimoto's and 48 Graves' patients to native thyroid microsomes, denatured and reduced human TPO and several recombinant fragments of human TPO corresponding to amino acids 457-933 of the native protein. Both Graves' and Hashimoto's sera bound native, denatured and reduced TPO at significantly greater rate than normal controls, and no differences were noted between the two disorders in binding to these forms of the autoantigen. Binding was also noted to two recombinant fragments of TPO, corresponding to amino acids 513-633 and 633-933 in TPO. The frequency of autoantibodies to the TPO AA(633-933) region was not significantly different in Hashimoto's vs. Graves' disease patients (58% vs. 65% respectively), and appeared to relate to evidence of glandular inflammation in the Graves' patients (presence of anti-thyroglobulin antibodies and elevated anti-microsomal antibody levels). In contrast, antibodies to the TPO AA(513-633) fragment were significantly more common and of higher titer in Hashimoto's vs. Graves' disease patients, and did not correlate with any measure of glandular inflammation. These results identify two specific regions of TPO autoantibody binding and indicate that there are differences in the autoantibody response to TPO in Hashimoto's and Graves' diseases.