Objective: AGEs, compounds formed by the transformation of proteins, are increased in conditions of oxidative stress and promote inflammation 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/sRAGE interaction play a role in the pathogenesis of several diseases related to oxidative stress. Recently, increased levels of AGEs, as specific markers of oxidative stress, have been reported in HT, but no data are available on sRAGE levels in these patients.
Materials And Methods: We enrolled 50 euthyroid HT patients (5 M e 45 F, mean age 38.5±12 yr) and 50 age- and sex-matched healthy controls. All subjects were eythyroid at time of recruitment (mean TSH value 1.98±1.10 uIU/ml in HT vs 1.40±0.73 mIU/ml in controls; P=0.689) and none was on LT-4 therapy. Smokers, subjects with kidney failure, history of cancer or autoimmune, inflammatory and infection comorbidities were excluded. Patients did not differ significantly from controls with regard to the main metabolic and anthropometric parameters. In sera from each subject, sRAGE levels were measured by ELISA (kit sRAGE Elisa, R&D System, Minneapolis, USA; minimum detectable dose 3 pg/ml); AGEs were determined on spectrophotometric method.
Results: sRAGE levels were significantly lower in HT patients (median 424 pg/ml, range 3071070) compared to controls (738 pg/ml, 3651205; P=0.001), while AGEs levels were significantly higher in TH than in controls (median: 205 AU/g prot, range 38463 vs 114 AU/g prot, range 30325; P=0.0001) and the two parameters were inversely correlated (r=−0.377; P=0.016). The correlation analysis also showed a positive correlation between BMI and serum AGEs levels. On the contrary, the sRAGE levels showed significantly inverse correlations with BMI and anti-thyroid antibodies positivity (r=−0.27, P=0.001). In regression analysis models, adjusted for BMI, serum Ab-TPO were the main predictors for both AGEs (P=0.014) and sRAGEs (P=0.027), irrespective of TSH and/or FT4 values.
Conclusion: sRAGE levels were decreased and AGEs increased in HT patients. Autoimmunity per se seems to play a role in AGEs/sRAGE imbalance, irrespective of thyroid function impairement. Given the protective effects of sRAGE, HT subjects may exhibit increased susceptibility to oxidative damage, even when in euthyroid status.
18 - 21 May 2019
European Society of Endocrinology