Thyroglobulin autoantibodies switch to immunoglobulin ( Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131 I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies

The subclass distribution of thyroglobulin autoantibodies ( TgAb) is debated, whereas their epitope pattern is restricted. Radioidine (¹³¹ I) treatment for Graves' disease ( GD) induces a rise in TgAb levels, but it is unknown whether it modifies subclass distribution and epitope pattern of TgAb as well. We collected sera from GD patients before ¹³¹ I treatment and 3 and 6 months thereafter. We measured total TgAb, TgAb light chains and TgAb subclasses by enzyme-linked immunosorbent assay ( ELISA) in 25 patients. We characterized the TgAb epitope pattern in 30 patients by inhibiting their binding to ^{125- I}Tg by a pool of four TgAb- Fab (recognizing Tg epitope regions A, B, C and D) and to Tg in ELISA by each TgAb- Fab. Total TgAb immunoglobulin ( Ig)G rose significantly ( P = 0·024). TgAb κ chains did not change ( P = 0·052), whereas TgAb λ chains increased significantly ( P = 0·001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after ¹³¹ I ( P = 0·008 and P = 0·006, respectively), while IgG2 and IgG4 levels did not change. The rise of IgG1 was persistent, that of IgG3 transient. The levels of inhibition of TgAb binding to Tg by the TgAb- Fab pool were comparable. A slight, non-significant reduction of the inhibition by the immune-dominant TgAb- Fab A was observed 3 and 6 months after ¹³¹ I. We conclude that ¹³¹ I treatment for GD increases the levels of the complement-activating IgG1 and IgG3 subclasses and does not influence significantly the epitope pattern of TgAb. In autoimmune thyroid disease subclass distribution of autoantibodies is dynamic in spite of a stable epitope pattern. [ABSTRACT FROM AUTHOR]