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Restricted thyroglobulin antibody epitope specificities in subjects with type 1 diabetes mellitus

O Okosieme, Medicine, Prince Charles' Hospital, Merthyr Tydfil, United Kingdom
C Wijeyaratne, Obstetrics, Faculty of Medicine, Colombo, Sri Lanka
J Lazarus, Centre for Endocrine & Diabetes Sciences, Cardiff University School of Medicine, Cardiff, United Kingdom
L Premawardhana, Medicine, Caerphilly Miners' Hospital, Caerphilly, CF83 2WW, United Kingdom

Correspondence: Lakdasa Premawardhana, Email: Premawardhanald{at}cardiff.ac.uk

Objectives: Following iodisation in Sri Lanka we observed a high prevalence of thyroglobulin antibodies (TgAbs) in type 1 diabetic (T1DM) patients. The clinical significance of these TgAbs is uncertain. We sought to obtain a detailed epitope analysis of TgAbs in T1DM patients recruited from diabetes clinics and to compare these with TgAb epitope specificities in patients with autoimmune thyroid disease (AITD) and healthy individuals in that country.

Design and methods: We used a panel of 10 thyroglobulin monoclonal antibodies (Tg-Mabs) in competitive ELISA reactions in a prospective study of subjects recruited from Colombo, to determine the epitopes recognised by TgAb-positive patients with T1DM (n=58, 34F:24M, median age 16 years), AITD patients (n=42, 33F:9M, median age 37 years) and healthy subjects (n=50, 39F:11M, median age 27 years). The outcomes were a comparison of reactivity with 6 Tg clusters (I-VI) in these subjects, and the relation of epitope specificity patterns with free thyroxine (FT4) and TSH.

Results: Patients with T1DM and AITD but not healthy control subjects preferentially recognised the immunodominant clusters, I, III and IV. Patients with these narrow epitope specificities had higher median TSH levels (1.60 vs 1.06; P=0.01), and were more frequently positive for TPOAb than those with broad specificities (52.3% vs 7.1%; P=0.004).

Conclusions: The TgAb epitope specificities in euthyroid Sri Lankans with T1DM are similar to AITD patients. TgAb epitope studies may potentially identify type 1 diabetic patients at risk of thyroid dysfunction