Multicenter study on TGPO autoantibody prevalence in various thyroid and non-thyroid diseases; relationships with thyroglobulin and thyroperoxidase autoantibody parameters

Abstract

Objective: TGPO autoantibodies (aAbs) that bind simultaneously to thyroglobulin (Tg) and thyroperoxidase (TPO) are present in the serum of patients with autoimmune thyroid diseases (AITD) and have been found to differ from monospecific Tg and TPO aAbs. To obtain further insights on the prevalence defined as the rate of occurrence and significance of TGPO aAbs in a large population, we carried out a collaborative study involving 15 European teams. Methods: Serum samples from 3122 patients with various thyroid and non-thyroid diseases and normal subjects were assayed using a novel TGPO aAb detection kit. This test was designed so that TGPO aAbs are trapped between the Tg-coated solid phase and the soluble TPO labeled with a radioiodinated monoclonal antibody. Results: Only three out of the 220 normal subjects (prevalence of 1.4%) were found to have positive TGPO aAb levels, which were mainly observed in the patients with AITD: the group of patients suffering from Hashimoto's thyroiditis had a TGPO aAb prevalence of 40.5% (n ¼ 437 patients), those with Graves' disease, a prevalence of 34.6% (n ¼ 645) and those with post-partum thyroiditis, 16.0% (n ¼ 243). Among the non-AITD patients with positive TGPO aAb levels, the TGPO aAb prevalence ranged from 20.7% among those with thyroid cancer (n ¼ 246) to 0% among those with toxic thyroid nodules (n ¼ 47). Among the patients with non-thyroid diseases, the TGPO aAb prevalence ranged from 9.8% in the case of Biermer's pernicious anemia (n ¼ 78) to 0% in that of premature ovarian failure (n ¼ 44). It is worth noting that the groups showing the highest TGPO aAb prevalence also contained the patients with the highest TGPO aAb titers. Statistical comparisons between the TGPO aAb prevalences in the various groups showed that TGPO aAb could be used as a parameter to distinguish between the groups of Hashimoto's and Graves' patients and between the women with post-partum thyroiditis and the post-partum women with only Tg and/or TPO aAb established during early pregnancy. Unexpectedly, the correlations between TGPO aAbs and Tg and TPO aAbs were found to depend mainly on the assay kit used. Conclusion: High TGPO aAb titers are consistently associated with AITD but the reverse was not found to be true. TGPO aAbs are a potentially useful tool, however, for establishing Hashimoto's diagnosis, and would be worth testing in this respect with a view to using them for routine AITD investigations.

Glycopolymers from Saccharomyces Cerevisiae BIM Y-195 with Unusual Immunochemical Properties: Isolation, Structural Identification and Prediction of Their Role in Pathogenesis/Treatment of Autoimmune Thyroid Diseases

“…We unexpectedly show that the structure of both BPs is identitical, which is in accord with (i) the presence of common B cell and T cell epitopes shared between TPO and Tg (Hoshioka et al, 1994;Kohno et al, 1988;McLachlan and Rapoport, 1989) and (ii) the existence of the circulating autoantibodies with dual specificity for Tg and TPO that were detected in the serum of rabbits immunized with Tg and commonly present in serum of peoples diagnosed with HT (Estienne et al, 1999;Ruf et al, 1994;Thrasyvoulides and Lymberi, 2004). Unfortunately, common B cell epitopes shared between TPO and Tg were not identified up to date, probably, due their conformational or/and cryptic nature or because of their production through the mechanism of epitope spreading.…”

Anti-thyroidal peroxidase antibodies are associated with thyrotropin levels in hypothyroid patients and in euthyroid individuals

“…Consequently, thyroid cell damage, as well as direct enzyme blocking, may lead to insufficient hormone production, occasionally preceded by transient hyperthyroidism [2]. Both hypo-and hyperthyroidism are among the most common endocrine disorders [3,4,5]. In addition, elevated titers of anti-TPO were revealed in a wide range of diseases affecting various body organs, including Biermer's pernicious anaemia, viral hepatitis treated with INFα, systemic lupus erythematosus, insulin-dependent diabetes mellitus, breast cancer, vitiligo [6] and thyroid nodular disease [7,8].…”

Aspects of Humoral Immunity in a Group of Children With Type 1 Diabetes and Thyroid Disorders

“… UK: study on 65 patients with Hashimoto's thyroiditis and on 38 patients with Graves-Basedow disease showed that antiTPO antibodies were positive in 86% of those with Hashimoto's thyroiditis and 87% of GravesBasedow disease: ifn the case of antiTg antibodies, the proportion of positive results was much lower, 58% and 73% (Gilmour et al, 2000)  Serbia: antiTPO antibodies were positive in almost all patients with Hashimoto's thyroiditis and 75% of patients with Graves-Basedow disease (Trbojevic et al, 2005)  France: antiTPO antibodies were present in 40.5% of patients with Hashimoto thyroiditis and 34.6% of Graves-Basedow disease (Estienne et al, 1999)  Germany: from 659 patients, 15.4% had elevated antiTPO AB and 14.4% antiTg AB, girls were more affected than boys (Kordonouri et al, 2005)  Poland: on a sample of 219 children and adolescents, the authors found higher titre of antiTPO AB in 34.7% of cases, also predominantly in females (Kalicka-Kasperczyk et al, 2003) In our study, regarding the presence of ACAT, significant differences were found between their titres in patients with Graves-Basedow disease and ACT (autoimmune diseases) than those with diffuse euthyroid goiter ( Table 4).…”