Objective: Advanced glycation end products (AGEs) increased oxidative stress and promote inflammation, resulting in the cellular damage, by interacting with their receptor (RAGE) on cell membrane. By contrast, the soluble receptor for AGE (sRAGE), that is proteolytically cleaved from cell surface receptor via matrix metalloproteinases, sequester RAGE ligands and act as a cytoprotective and anti-inflammatory agent. AGEs-RAGE/sRAGE interaction is deemed to play a role in the pathogenesis of several disease related to oxidative stress. Moreover, oxidative stress has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Mostly, it has been correlated to thyroid dysfunction, but recently increased levels of AGEs have been reported in adult individuals suffering from euthyroid Hashimotos thyroiditis (HT) (Ruggeri et al. Thyroid 2016). No data are available on such oxidative stress parameters in pediatric HT patients. The aim of our study was to investigate the changes in oxidative balance in pediatric patients with euthyroid HT.
Materials and Methods: We enrolled 19 HT pediatric patients (3 M, 16 F; mean age 12.3±2.4 year) and 18 age- and sex-matched healthy controls (6 M, 12 F; mean age 12.0±2.4 year). None was on L-T4 therapy. Exclusion criteria: autoimmune, inflammatory and infection comorbidities. Patients did not differ significantly from controls with regard to lipid and glucidic profile neither for anthropometric parameters. In sera from each subject, sRAGE levels were measured by ELISA (kit sRAGE Elisa, R&D System, Minneapolis, USA). AGEs, compounds formed by the transformation of proteins, were determined on spectrophotometric detection.
Results: sRAGE levels were significantly lower in HT patients (median 414.30 pg/ml, range 307.30850.30) than in controls (558.30, 265.801132.30; P=0.046). These values correlated negatively with BMI (r=−0.365, P=0.026) and anti-thyroid antibodies positivity (r=−0.364, P=0.027), irrespective of TSH values and thyroid functional status. No differences emerged between patients and controls with regard to serum AGEs (124.25 AU/g prot, 71.98186.72 vs 139.26, 94.06251.05, P=0.358).
Conclusions: sRAGE levels were decreased in HT children/adolescents, and autoimmunity per se seem to play an important role in such a reduction of sRAGE, irrespective of any functional alteration. Given the protective effects of sRAGE, children and adolescents suffering from HT may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology