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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., (© 2014 British Society for Immunology.)

Background: No long-term follow-up data are available for differentiated thyroid carcinoma (DTC) patients prepared with either exogenous or endogenous TSH and treated with low-activity (1.1 GBq [30 mCi]) radioiodine (¹³¹I)., Aim: The aim of this study was to evaluate the 10-year follow-up of DTC patients who underwent remnant ablation with 1.1 GBq ¹³¹I after l-T4 withdrawal, recombinant human TSH (rhTSH) administration, or both., Patients: A total of 159 DTC patients treated with total thyroidectomy and 1.1 GBq (30 mCi) of ¹³¹I for remnant ablation and stimulated with rhTSH and/or endogenous TSH were separated into ablated (n = 115) and not ablated (n = 44) patients and prospectively followed-up for at least 10 years. In addition, we evaluated several features that could correlate with the final status of patients., Results: During the follow-up, 4 of 115 (3.5%) ablated patients showed a recurrence and 1 was successfully cured. Among not ablated patients, 16 of 44 (36.4%) had a persistent disease. At the end of the 10-year follow-up, 140 of 159 (88.1%) patients were disease-free, whereas 19 of 159 (11.9%) remained affected. No correlation was found with the type of TSH stimulation, and no other clinical and pathological features showed any correlation with the final status. However, low levels of stimulated serum thyroglobulin (<5.4 ng/mL) at first control after remnant ablation identified a subgroup of not ablated patients who became spontaneously cured., Conclusions: Long-term outcomes are similar in DTC patients treated with 1.1 GBq (30 mCi) ¹³¹I and prepared either with rhTSH or endogenous TSH. It is of interest that serum thyroglobulin at first control after ablation can have a prognostic role.

Context: Congenital hypothyroidism (CH) associated with goiter or a gland of normal size has been linked to dual oxidase 2 (DUOX2) mutations in the presence of iodide organification defect., Objective: Thirty unrelated children with CH or subclinical hypothyroidism (SH) identified during infancy with a eutopic thyroid gland, coming from our Screening Centre for CH or referred from other regions of Italy, were studied with the perchlorate discharge test to identify organification defects. Eleven children with iodide organification defect were considered for the genetic analysis of TPO, DUOX2, and dual oxidase maturation factor 2 (DUOXA2) genes., Patients: Eight children with CH and three with SH and eutopic thyroid gland were included in the study. After discontinuation of therapy, a partial or complete organification defect was shown after ¹²³I scintigraphy and perchlorate test., Methods: TPO, DUOX2, and DUOXA2 genes were analyzed, and functional activity of DUOX2 variants was studied in HeLa cells., Results: Sequencing of the DUOX2 gene revealed a deletion S965fsX994 in three children; two were euthyroid after 1 month of L-T₄ discontinuation but developed SH after 5 and 18 months, respectively, whereas the other child had SH. One child with SH showed H678R, R701Q, and P982A substitutions, and another child with SH showed only the P982A. One child with SH showed the Y1150C mutation, and another euthyroid child showed the A728T mutation. Functional studies confirmed that S965fsX994, Y1150C, and A728T mutations were responsible for the defect in H₂O₂ production, whereas H678R, R701Q, and P982A did not alter H₂O₂ production in vitro., Conclusions: Genetic analysis of the DUOX2 gene was performed in 11 children with organification defect. Two new mutations (Y1150C and A728T) and the deletion S965FsX994 were responsible for the deficit in the organification process and the phenotypes. Three polymorphisms (H678R, P982A, and R701Q) were identified.

Context: Some cases of congenital hypothyroidism (CH) are associated with a gland of normal size., Objective: To explore the cause of organification defect in one child with CH and a eutopic thyroid gland, genetic analyses of TPO, DUOX2, and DUOXA2 genes were performed., Patient: One child with CH, a eutopic thyroid gland, and a partial organification defect was shown after (123)I scintigraphy and perchlorate test., Methods: In the child with the organification defect, TPO, DUOX2, and DUOXA2 genes were analyzed. The functional activity of the DUOX2 mutants was studied after expression in eukaryotic cells., Results: No TPO or DUOXA2 gene mutations were identified. Direct sequencing of the DUOX2 gene revealed a compound heterozygous genotype for S911L and C1052Y substitutions. S911L and C1052Y caused a partial defect in H(2)O(2) production after transient expression in HeLa cells., Conclusions: We performed a genetic analysis in one child with CH and a eutopic thyroid gland. Two new mutations in DUOX2 gene responsible for the partial deficit in the organification process were identified.