AUTOANTIBODIES TO THYROID-HORMONES - THE ROLE OF THYROGLOBULIN

Autoantibodies against thyroid hormones (THAA) are frequently detected in the sera of patients with thyroid disorders together with autoanti bodies against thyroglobulin (TGAA). THAA are considered to be a subse t of TGAA, but alternative possibilities have not been excluded. We hy pothesize that if THAA arise through an immune response to iodothyroni nes carried by circulating thyroglobulin (hTg), THAA should be found t ogether with autoantibodies against the peptide backbone of hTg (TPAA) close to the hormone-forming sites. We measured TPAA in 178 serum sam ples, obtained from healthy subjects and patients with thyroid disorde rs, using two hormone-forming peptides isolated from hTg. The occurren ce of TPAA was much lower than that of TGAA. Autoantibodies to the hor mone-rich peptide, P3, were significantly more common than autoantibod ies to the hormone-poor peptide, P1 (111/178 = 62.3% for TGAA versus 2 1/178 = 11.8% for anti-P3 TPAA and 7/178 = 3.9% for anti-PI TPAA). The presence of autoantibodies to thyroid hormones was investigated in 25 TTPAA(+) and 26 TPAA(-) sera. THAA were found more frequently in TPAA (+) sera (10/25 = 40% for TPAA(+) and 4/26 = 15.3% for TPAA(-)). Corre lation analysis shows that the anti-P3, but not the anti-P1 binding ac tivity, correlates positively with the THAA-binding activity (P < 0.00 1 for anti-T4 THAA; P < 0.01 for anti-T3 THAA). Specificity of anti-P3 TPAA indicates that a subset of the anti-P3 antibodies is directed ag ainst the thyroid hormone moiety and another subset is directed agains t the peptide backbone near tile hormone-forming peptide, according to our hypothesis. These results indicate that the THAA response is an a nti-hTg response directed, in a significant number of cases, against t he hormone-forming site included in the P3 peptide. This response seem s to be elicited by either native hormone-rich hTg or by hTg fragments .