[Autoantigens in autoimmune thyroid diseases]

Human thyroid peroxidase (TPO) was found to bind with both IgG and IgM from patients with autoimmune thyroid diseases. Furthermore, binding of IgG to microsomes was inhibited by TPO. Patients' IgG that passed through an antigen column packed with TPO-coupled Sepharose 4 B beads lost their hemagglutinating activity in microsome hemagglutination test. Various strains of mice were immunized with porcine TPO emulsified in complete Freund's adjuvant. Both C 57 BL/6 and C 57 BL/10 mice showed mononuclear cell infiltration in the thyroid with very high incidences of thyroiditis. The strains of mice showing thyroiditis were very different from high responder strains that were immunized with murine thyroglobulin. Cloning of human TPO cDNA was attempted to deduce the primary structure of human TPO. Using three kinds of oligonucleotides as probes, two cDNAs, 2.8 and 2.4 kb, were selected from a cDNA library constructed from mRNA purified from Graves' disease thyroid. Sequencing of cDNAs revealed that shorter cDNA lacked 171 nucleotides at the middle portion of the longer cDNA. Primer extension analysis of mRNA indicated that the full length cDNA of human TPO consists of 3,048 nucleotides and its open reading frame codes 933 amino acids.