Clinical significance of thyroglobulin antibodies and thyroid peroxidase antibodies in Graves' disease: a cross-sectional study.

PURPOSE: The significance of thyroglobulin antibodies (TgAbs) and thyroid peroxidase antibodies (TPOAbs) in Graves' disease (GD) remains unclear. Therefore, this study aimed to clarify the clinical significance of TgAbs and TPOAbs in GD. METHODS: A total of 442 patients with GD were recruited and divided into four groups based on TgAb and TPOAb positivity. Their clinical parameters and the characteristics of the groups were compared. Cox proportional hazard regression analysis was performed to assess risk factors for GD remission. RESULTS: The free triiodothyronine (FT3) level was significantly higher in groups positive for TgAbs and TPOAbs than in the other groups. The FT3 to free thyroxine (FT4) (FT3/FT4) ratio was significantly higher and thyrotropin-stimulating hormone (TSH) receptor antibodies (TRAbs) were significantly lower in the TgAb+/TPOAb- group. Time to FT4 recovery was significantly shorter for groups negative for TPOAbs, whereas time to TSH recovery was significantly longer for groups positive for TPOAbs. Cox proportional hazard regression analysis revealed that TgAb positivity, prolonged treatment duration with antithyroid drugs, and Graves' ophthalmopathy treated with methylprednisolone were significantly associated with GD remission and that a smoking history, elevated FT3/FT4 ratio, and treatment with propylthiouracil hindered GD remission. CONCLUSION: The contributions of TgAbs and TPOAbs to GD pathogenesis differ. Patients positive for TgAbs develop GD with lower TRAb titers and undergo earlier remission than those negative for TgAbs. Patients positive for TPOAbs develop GD with high TRAb titers and need a long time to achieve remission.

Critical Amino Acid Variants in HLA-DRB1 and -DQB1 Allotypes in the Development of Classical Type 1 Diabetes and Latent Autoimmune Diabetes in Adults in the Japanese Population.

The effects of amino acid variants encoded by the human leukocyte antigen (HLA) class II on the development of classical type 1 diabetes (T1D) and latent autoimmune diabetes in adults (LADA) have not been fully elucidated. We retrospectively investigated the HLA-DRB1 and -DQB1 genes of 72 patients with classical T1D and 102 patients with LADA in the Japanese population and compared the frequencies of HLA-DRB1 and -DQB1 alleles between these patients and the Japanese populations previously reported by another institution. We also performed a blind association analysis with all amino acid positions in classical T1D and LADA, and compared the associations of HLA-DRB1 and -DQB1 amino acid positions in classical T1D and LADA. The frequency of DRß-Phe-13 was significantly higher and those of DRß-Arg-13 and DQß-Gly-70 were significantly lower in patients with classical T1D and LADA than in controls. The frequencies of DRß-His-13 and DQß-Glu-70 were significantly higher in classical T1D patients than in controls. The frequency of DRß-Ser-13 was significantly lower and that of DQß-Arg-70 was significantly higher in LADA patients than in controls. HLA-DRß1 position 13 and HLA-DQß1 position 70 could be critical amino acid positions in the development of classical T1D and LADA.

Critical amino acid variants in HLA-DRB1 allotypes in the development of Graves' disease and Hashimoto's thyroiditis in the Japanese population.

The effects of amino acid variants encoded by human leukocyte antigen (HLA) class II on the development of Graves' disease (GD) and Hashimoto's thyroiditis (HT) have not been fully elucidated. We investigated the HLA-DRB1 genes of 243 GD patients and 82 HT patients in the Japanese population and compared the frequencies of HLA-DRB1 alleles and HLA-DRB1 amino acid variants between these patients and the Japanese populations previously reported by another institution. The frequencies of HLA-DRB1*04:05 and -DRB1*14:03 alleles were significantly higher and those of HLA-DRB1*01:01 and -DRB1*15:02 alleles were lower in GD patients than in controls. The frequencies of HLA-DRB1*08:03 and -DRB1*09:01 alleles were significantly higher and that of the HLA-DRB1*13:02 allele was lower in HT patients than in controls. A blind association analysis with all amino acid positions identified DRß9 and DRß31 for GD and DRß9, DRß13, and DRß21 for HT. The frequency of Glu-9 was significantly higher and that of Cys-9 was lower in GD patients than in controls. The frequencies of Lys-9 and Phe-13 were significantly higher in HT patients than in controls. DRß9 and DRß13 could be critical amino acid positions in the development of GD and HT.

Association of Autoimmune Thyroid Disease with Anti-GAD Antibody ELISA Test Positivity and Risk for Insulin Deficiency in Slowly Progressive Type 1 Diabetes.

The presence of antiglutamic acid decarboxylase antibody (GADA) is required for the diagnosis of slowly progressive type 1 diabetes (SPT1D). We examined the factors influencing GADA determination by radioimmunoassay (GADA-RIA) and by enzyme-linked immunosorbent assay (GADA-ELISA). Sixty patients with SPT1D and 154 patients with type 2 diabetes were examined by both GADA-RIA and GADA-ELISA and for the presence of autoimmune thyroid disease (AITD). We compared the clinical characteristics of these patients based on the positivity or negativity of GADA-RIA and GADA-ELISA, and the existence or nonexistence of AITD. Thirty of 60 (50.0%) GADA-RIA-positive patients were GADA-ELISA negative, whereas none of the 154 GADA-RIA-negative patients were GADA-ELISA positive. Concomitant AITD was significantly less in patients with GADA-RIA and without GADA-ELISA and was significantly more in patients with GADA-RIA and GADA-ELISA. In GADA-RIA-positive patients, there was no significant difference in the GADA-RIA titer among the GADA-ELISA-negative patients with and without AITD, and the GADA-ELISA-positive patients without AITD; whereas the frequency of insulin deficiency was significantly higher in the patients with AITD and/or GADA-ELISA than in those without AITD and GADA-ELISA. Examination of GADA-ELISA and AITD in GADA-RIA-positive patients might be useful in predicting insulin deficiency in these patients.