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

• Published in: Clinical and experimental immunology 2014-12, Vol.178 (3), p.438-446
• Main Authors: Latrofa, F, Ricci, D, Montanelli, L, Piaggi, P, Mazzi, B, Bianchi, F, Brozzi, F, Santini, P, Fiore, E, Marino, M, Tonacchera, M, Vitti, P
• Format: Article
• Language: English
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1111/cei.12438

The subclass distribution of thyroglobulin autoantibodies (TgAb) is debated, whereas their epitope pattern is restricted. Radioidine ( super(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 super(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 super(125-) super(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 Kappa chains did not change (P=0.052), whereas TgAb lambda chains increased significantly (P=0.001) and persistently. We observed a significant rise in IgG1 and IgG3 levels after super(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 super(131)I. We conclude that super(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.