Untreated Graves' but not Remission Graves' Immunoglobulin G Preparations Increase Intracellular Ca2+ in FRTL-5 Thyroid Cells

We compared immunoglobulin G (IgG) preparations obtained from untreated Graves' patients with those from Graves' patients in remission and normal subjects in terms of their activity to stimulate the phospholipase C-Ca2+ signaling. Ca2+ mobilizing activity of the untreated Graves' IgG preparations in FRTL-5 thyroid cells was statistically (P<0.01) and significantly higher than the activity of normal IgG preparations, whereas there was no significant difference in the activity between the remission Graves' and normal IgG preparations. Digital video imaging of fura2-loaded FRTL-5 cells confirmed that the Ca2+ mobilizing action of the untreated Graves' IgG preparations is an intracellular event. Phospholipase C activation by the untreated but not remission Graves' IgG preparations was statistically higher than that by normal IgG preparations. Involvement of the phospholipase C activation in the Ca2+ response mechanism was confirmed by the enhancement of the Ca2+ response by an adenosine derivative, N6(L-2-phenylisopropyl)adenosine (PIA) which can potentiate agonist-induced phospholipase C activation but not the Ca2+ mobilization itself. The Ca2+ response to the IgG preparations did not show a significant correlation with their cAMP response (TSAb). Therefore, the Ca2+ response to Graves' IgG preparations may be utilized as a functional marker for Graves' disease in addition to TSAb.