Research Article Effect of Advanced Glycation End Products on Human Thyroglobulin’s Antigenicity as Identified by the Use of Sera from Patients with Hashimoto’s Thyroiditis and Gestational Diabetes Mellitus A. Hatzioannou, 1 I. Kanistras, 1 E. Mantzou, 2 E. Anastasiou, 3 M. Peppa, 4 V. Sarantopoulou, 3 P. Lymberi, 1 and M. Alevizaki 2 1 Immunology Laboratory, Immunology Department, Hellenic Pasteur Institute, 127 Vasilissis Sofas Avenue, 11521 Athens, Greece 2 Endocrine Unit Athens University, Evgenideion Hospital, 20 Papadiamantopoulou Street, 11528 Athens, Greece 3 Endocrine Unit, Department of Medical Terapeutics, Alexandra Hospital, Athens University School of Medicine, 80 Vasilissis Sofas Avenue, 11528 Athens, Greece 4 Department of Geriatrics, Mt Sinai School of Medicine, 1468 Madison Avenue, New York, NY 10029, USA Correspondence should be addressed to P. Lymberi; plymberi@pasteur.gr Received 3 April 2015; Revised 19 June 2015; Accepted 21 June 2015 Academic Editor: Małgorzata Kotula-Balak Copyright © 2015 A. Hatzioannou et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Advanced glycation end products (AGEs) are formed on proteins afer exposure to high concentrations of glucose and modify protein’s immunogenicity. Herein, we investigated whether the modifcation of thyroglobulin (Tg) by AGEs infuences its antigenicity and immunogenicity. Human Tg was incubated in vitro with increasing concentrations of D-glucose-6-phosphate in order to produce Tgs with diferent AGE content (AGE-Tg). Native Tg and AGE-Tgs were used in ELISA to assess the serum antibody reactivity of two patient groups, pregnant women with gestational diabetes (GDM), and patients with Hashimoto’s thyroiditis (HT). We produced in vitro AGE-Tg with low and high AGE content, 13 and 49 AGE units/mg Tg, respectively. All HT patients’ sera presented the same antibody reactivity profle against native Tg and AGE-Tgs, indicating that the modifcation of Tg by AGEs did not alter its antigenicity. Similarly, the GDM patients’ sera did not discriminate among the two forms of Tg, native or artifcially glycated, suggesting that the modifcation of Tg by AGEs might not alter its immunogenicity. Te modifcation of Tg by AGEs has no obvious efect on neither its antigenicity nor, most likely, its immunogenicity. It seems that other Tg modifcations might account for the production of aTgAbs in patients with GDM. 1. Introduction Advanced glycation involves a chain of chemical reactions initiated by the nonenzymic, covalent binding of reducing sugars to protein amino groups (Schif base and Amadori adducts). Additional reactions take place, leading to the formation of a heterogeneous family of sugar-amino acid adducts, collectively known as advanced glycation end prod- ucts (AGEs) [1]. N-(carboxymethyl)lysine (CML) is a com- monly formed AGE. Glycated hemoglobin (HbA1c) is one of the most studied glycated proteins, derived from the nonenzymic reaction between the valine and lysine amino groups of hemoglobin and glucose [2], and is commonly used in clinical practice as an indicator of glycemic control [3, 4]. Recent studies point towards a strong association between AGEs and HbA1c serum levels [5, 6]. Te spontaneous modifcation of proteins by AGE for- mation occurring in vivo may increase their immunogenicity and lead to the induction of specifc antibodies, such as antibodies against AGE-modifed serum albumin, IgG, low- density lipoprotein (LDL), and factor VIII, as demonstrated in the sera from patients with diabetes or rheumatoid arthritis, as well as from healthy subjects [7–12]. Te mod- ifcation of proteins by AGEs has been suggested to be responsible for some of the complications encountered in diabetic patients; the immune complexes formed between Hindawi Publishing Corporation International Journal of Endocrinology Volume 2015, Article ID 849615, 7 pages http://dx.doi.org/10.1155/2015/849615