The upper reference limit for thyroid peroxidase autoantibodies is method-dependent: A collaborative study with biomedical industries.

BACKGROUND: The determination of the upper reference limit (URL) for thyroid peroxidase autoantibodies (TPOAbs) is a contentious issue, because of the difficulty in defining the reference population. The aim of this study was to establish the URL (eURL) for TPOAbs, according to the National Academy of Clinical Biochemistry (NACB) guidelines and to compare them with those obtained in a female counterpart, by the use of six commercial automated platforms. METHODS: 120 healthy males and 120 healthy females with NACB-required characteristics (<30years, TSH between 0.5 and 2.0mIU/L, normal thyroid ultrasound, without personal/family history of thyroid and non-thyroid autoimmune diseases) were studied. Sera were analyzed for TPOAbs concentration using six immunoassay methods applied in automated analyzers: Advia Centaur XP (CEN), Siemens Healthcare Diagnostics; Maglumi 2000 Plus, Shenzen New Industries Biomedical Engineering; Architect ci4100, Abbott; Cobas e411 (COB) Roche Diagnostics; Unicel DxI (UNI) and Lumipulse G1200, Fujirebio. RESULTS: Within each method, TPOAbs values had a high degree of dispersion and the eURLs were lower than those stated by the manufacturer. A statistically significant difference (p<0.05) between medians of males and females was observed only for COB and for UNI. However, the comparison of the male and female proportions positive for TPOAbs using the eURL of the counterpart, showed the lack of clinical significance of the above differences (Chi-square test, p>0.05). CONCLUSIONS: Despite the analytical harmonization, the wide dispersion of the results and the differences of the eURLs between methods suggest the need of further studies focusing on TPO antigen preparations as the possible source of variability between different assays. In addition, the lack of clinical significant difference between males and females, in terms of TPOAb eURLs, confirms the suitability of the NACB recommendations.

Autoantibodies to parietal cells as predictors of atrophic body gastritis: a five-year prospective study in patients with autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITD) can be associated with autoimmune gastritis (AIG), but the frequency of this association is poorly characterized. We performed a prospective study to: a) characterize the frequency of parietal cell (PCA) and intrinsic factor (IFA) autoantibodies in AITD patients; b) evaluate the development of histologically- and functionally-proven AIG after five years and to assess the predictive role of PCA for AIG at baseline; and c) analyze the trend of PCA levels in the course of the disease. We studied 208 consecutive adult patients affected by AITD (166 Hashimoto's thyroiditis, 42 Graves' disease). PCA, IFA and plasma gastrin levels were measured with ELISA methods at baseline and after 5years. At baseline, 51/208 (24.5%) AITD patients were positive for PCA and 10/208 (4.8%) for IFA. 25 out of 54 PCA/IFA-positive AITD patients (all without gastric or haematologic symptoms) agreed to participate in the follow-up study. After 5years, 6 (24%) of these 25 patients showed a histologically proven AIG, with lymphocytic infiltration and/or atrophy of body gastric mucosa. The trend analysis of PCA concentration showed that autoantibody levels rise progressively over time, reach a peak level and then fall, according to the progressive destruction of gastric mucosa and to the disappearance of the target autoantigen (proton pump). The presence of PCA predicts the development of autoimmune gastritis in AITD patients. Antibody levels measured with a sensitive quantitative immunometric method are useful for early diagnosis and early treatment of the disease.