CLINICAL STUDY Restricted thyroglobulin antibody epitope specificities in subjects with type 1 diabetes mellitus O E Okosieme, C N Wijeyaratne 1 , J H Lazarus 2 and L D K E Premawardhana 2,3 Department of Endocrinology and Diabetes, Prince Charles Hospital, Cwm Taff NHS Trust, Merthyr Tydfil, Mid Glamorgan CF47 9DT, UK, 1 Department of Obstetrics and Gynaecology, Faculty of Medicine, Kynsey Road, Colombo 7, Sri Lanka, 2 School of Medicine, Centre for Endocrine and Diabetes Sciences, Cardiff University, Cardiff CF14 4XN, South Wales, UK and 3 Department of Endocrinology and Diabetes, Caerphilly District Miner’s Hospital, St Martin’s Road, Caerphilly CF83 2WW, UK (Correspondence should be addressed to O E Okosieme; Email: onyebuchi.okosieme@wales.nhs.uk) Abstract 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 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 (nZ58, 34F:24M, median age 16 years), AITD patients (nZ42, 33F:9M, median age 37 years) and healthy subjects (nZ50, 39F:11M, median age 27 years). The outcomes were a comparison of reactivity with six Tg clusters (I–VI) in these subjects, and the relation of epitope specificity patterns with free thyroxine 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; PZ0.01), and were more frequently positive for antibodies to thyroid peroxidase than those with broad specificities (52.3 vs 7.1%; PZ0.004). Conclusions: The TgAb epitope specificities in euthyroid Sri Lankans with T1DM are similar to AITD patients. TgAb epitope studies may potentially identify T1DM patients at risk of thyroid dysfunction. European Journal of Endocrinology 161 489–493 Introduction Type 1 diabetes (T1DM) and autoimmune thyroid disease (AITD) are classic examples of organ-specific autoimmunity. Both conditions frequently coexist and up to one-third of patients with T1DM develop thyroid dysfunction during long-term follow-up (1). AITD is characterised by the presence of circulating antibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) (2). These antibodies occur more frequently in patients with T1DM than in healthy individuals (3). However, thyroid antibodies are also present in about 10% of healthy euthyroid individuals (4) and have been reported in 30% of healthy persons in newly iodised populations (5, 6). In the wake of iodine prophylaxis in Sri Lanka, we observed a high prevalence of TgAbs in various population subgroups (6). These TgAbs were not associated with thyroid dysfunction and probably represented a non-pathological antibody response to iodination (6). Recently, we also reported a high frequency of TgAbs in Sri Lankan patients with T1DM (7). The clinical significance of TgAbs in these diabetic patients is thus unclear and a point of interest is whether they indicate thyroiditis or whether they simply represent a non-pathological effect of iodination. Studies on TgAb epitope reactivity have provided a potential means of distinguishing the TgAbs seen in health from those seen in disease (8, 9). Tg, a large molecular weight (660-kDa) glycoprotein, is the major colloid protein and serves as a prohormone and storage protein for the thyroid hormones, thyroxine (T 4 ) and triiodothyronine (10). Detailed panels of murine Tg-MAbs have delineated several B-cell epitopes on Tg that are differentially recognised by sera from healthy individuals and AITD patients (11). These immunodo- minant Tg epitopes are located in the less conserved non-hormonogenic portions of the Tg molecule and are preferentially recognised by sera from the majority of AITD patients. On the other hand, healthy euthyroid individuals exhibit a broad or less-restricted Tg epitope reactivity pattern (8, 9, 12). The TgAb epitope specificities in patients with T1DM are unknown, and to the best of our knowledge have not been previously tested in any population group. European Journal of Endocrinology (2009) 161 489–493 ISSN 0804-4643 q 2009 European Society of Endocrinology DOI: 10.1530/EJE-09-0413 Online version via www.eje-online.org