MAJORITY OF THYROID PEROXIDASE AUTOANTIBODIES IN PATIENTS WITH AUTOIMMUNE THYROID-DISEASE ARE DIRECTED TO A SINGLE TPO DOMAIN

Murine monoclonal antibodies (mAb) produced against native human thyro id peroxidase (TPO) are powerful tools for analyzing the autoantibody (Aab) epitopes on TPO. Binding sites of thirteen mAbs cover all or mos t antigenic regions on TPO. We determined the competition between Aabs from 75 AITD patients and 13 mAbs in binding to TPO. Autoantibodies r ecognize predominantly the TPO area close or identical to mAb#9 epitop e. All sera tested inhibited this mAb binding by 92.9 +/- 14.8 (mean /- SD), range from 69-100%, AITD patients' sera with low Aabs titer up to 1/2,000 inhibited mAb#9 binding to TPO by 85 +/- 11.5% (mean +/- S D) and did not influence remaining mAbs binding to TPO, With elevated Aab levels the inhibition of other mAbs binding was higher, but never exceeded 35%. The amount of Aabs yielding 50% inhibition of mAbs bindi ng was lowest for mAb#9. In order to obtain this degree of inhibition for other mAbs 5 to 25 times more Aabs were needed. Our results demons trate that the majority of autoantibodies in sera of patients with AIT D recognize a single immunodominant region on the TPO mapped by mAb#9, They account for about 80-90% of serum TPO autoantibodies. The autoim mune response to other regions on TPO molecule is directed to several other epitopes, but represents quantitatively a minority of autoantibo dies. This response intensifies with increasing Aabs level in the seru m.