Autoantigenic Role of Variant Thyroperoxidase / 대한내분비학회지

ABSTRACT

Background: Thyroperoxidase(TPO) is one of the most important autoantigens in autoimmune thyroid disorders and autoantibody to TPO is found in almost every patients with various autoimmune thyroid diseases. Human TPO was already cloned and the completed nucleotide sequences are well known. In human thyroid tissues, several variants mRNA's of TPO are found in addition to the wild type. Especially the variants lacking exon 10(TPOΔexon10) and exon 16(TPOΔ exon16) are found in very large amount in both normal and Graves thyroid tissues. The significance of these variants TPO mRNAs are largely unknown. The authors tried to investigate the autoantigenic role of these variant TPO. Methods: To produce variant TPO cDNAs, oligonucleotide directed mutagenesis was performed using cDNA for wild type human TPO as template. The produced variants cDNAs were transfected into Cos-7 cells and variants TPO proteins were tested against patients sera showing high titers of anti-TPO antibody. Results: Seven of 12 Graves sera reacted with TPOΔexon 10 and 8 Graves sera with TPOΔ exonl6. Eight of 15 Hashimoto sera reacted TPOΔexon16 and 9 with TPOΔexon16. The reactivity with variants TPO was not related to clinical findings. Conclusion: These two variant TPOs, that is TPOexon10 and TPOΔexon16, could act as an autoantigen if they were translated in vivo, and could play a role in autoimmune thyroid disease. Their exact role in the pathogenesis of autoimmune thyroid disorders are to be clarified.