Objective: We studied a previously uncharacterized poly A(−) RNA transcript (designated Heg) in blood mononuclear cells and its relationship to TSH receptor autoantibodies and to CD14, Nucks, Cdk1, GCRα, NF-κB and CK2 mRNA.
Subjects and methods: The main study groups were a) normal subjects b) patients with early and untreated Graves disease and c) patients with Graves disease studied after treatment. Quantification of mRNA was done by RT-PCR-HPLC. The protocol study was approved by the local Ethics Committee.
Results: The sequence of the transcript was localized to a clone from the HUGO project. The 3′ end of the Heg gene overlaps the 3′ end of the Nucks gene. In 18 normal subjects, mean basal levels of specific RNA/mRNA were 0.15±0.01 (mean±S.E.M.), 1.3±0.07 and 30±3 amol/μg DNA for Heg, Nucks and CD14, respectively. In 17 patients with untreated Graves disease, concentrations of TSH receptor autoantibodies were negatively correlated to Heg RNA amol/μg DNA (P<0.001) and positively correlated to Cdk1 mRNA zmol/μg DNA (P<0.002) (r=0.83). In the combined group of treated patients with Graves disease and normal subjects CD14 was negatively correlated to Heg RNA amol/μg DNA (P<0.001). Nucks and CK2 mRNA were closely correlated (P<0.001). Inhibition of Cdk1 by a cyclin-dependent kinase inhibitor, Roscovitine, decreased CD14 mRNA markedly (P<0.001). Heg and Nucks siRNA elicited an immune reaction.
Conclusions: TSH receptor autoantibodies may be regulated by nuclear kinase activity (Cdk1) and the degree of apoptosis (Heg) in mononuclear cells. Drugs which inhibit Cdk1 may be of interest in the treatment of autoimmune disease.
03 - 07 May 2008
European Society of Endocrinology