title: Thyroglobulin autoantibodies switch to immunoglobulin (Ig)G1 and IgG3 subclasses and preserve their restricted epitope pattern after 131I treatment for Graves' hyperthyroidism: the activity of autoimmune disease influences subclass distribution but not epitope pattern of autoantibodies.
abstract: 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.
authors.affiliation: Endocrinology Unit, University Hospital of Pisa, Pisa, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Latrofa
authors.forename: D
authors.initials: D
authors.lastname: Ricci
authors.forename: L
authors.initials: L
authors.lastname: Montanelli
authors.forename: P
authors.initials: P
authors.lastname: Piaggi
authors.forename: B
authors.initials: B
authors.lastname: Mazzi
authors.forename: F
authors.initials: F
authors.lastname: Bianchi
authors.forename: F
authors.initials: F
authors.lastname: Brozzi
authors.forename: P
authors.initials: P
authors.lastname: Santini
authors.forename: E
authors.initials: E
authors.lastname: Fiore
authors.forename: M
authors.initials: M
authors.lastname: Marinò
authors.forename: M
authors.initials: M
authors.lastname: Tonacchera
authors.forename: P
authors.initials: P
authors.lastname: Vitti
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006111:Graves Disease / Q000276:immunology / Q000532:radiotherapy*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification*; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D013954:Thyroglobulin / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes; D013954:Thyroglobulin
keywords: B-cell epitopes; Graves’ disease; IgG subclasses; intramolecular epitope spreading; thyroglobulin autoantibodies