Regulation of TSH Receptor Autoantibodies by a long Non-Coding RNA (Heg) and Cdk1- A Review.

ABSTRACT

Aims: A substantial part of the genome is transcribed in non-coding RNAs. We review our finding of a long non-coding RNA (designated Heg) in mononuclear cells (MNC) and regulation of TSH receptor autoantibodies (TRAb). Results: The Heg RNA transcript in MNC is negatively correlated with TRAb in patients with early and untreated Graves’ disease. In treated patients and in controls Heg correlated negatively with CD14 mRNA. Transfection studies with fragments of Heg added to MNC (exogenous Heg) decreased CD14 mRNA in MNC and increased gene expression of RIG-I, TLR7 and IFN-γ. Heg is likely to activate TLR7 receptors. CD14 is a co-receptor of TLR7. Decrease in gene expression of CD14 after Heg is a sign of differentiation of MNC to dendritic cells. This may reduce surface expression of CD14, cytokine responses and the responsiveness to TSH receptor antigens. Thus the relationship between TRAb and lnc Heg RNA is most likely explained by receptor crossinterference. Cdk1 mRNA (an index of cell cycle activity) is positively related with TRAb. Cdk1 mRNA and TRAb but not Heg decreased significantly during antithyroid treatment. Cdk1 decreased to values below normal. Conclusion: Thus both Heg RNA and Cdk1 may regulate the level of TRAb but by two different mechanisms.