RESUMEN
The essential trace element selenium (Se) is needed for the biosynthesis of selenocysteine-containing selenoproteins, including the secreted enzyme glutathione peroxidase 3 (GPX3) and the Se-transporter selenoprotein P (SELENOP). Both are found in blood and thyroid colloid, where they serve protective functions. Serum SELENOP derives mainly from hepatocytes, whereas the kidney contributes most serum GPX3. Studies using transgenic mice indicated that renal GPX3 biosynthesis depends on Se supply by hepatic SELENOP, which is produced in protein variants with varying Se contents. Low Se status is an established risk factor for autoimmune thyroid disease, and thyroid autoimmunity generates novel autoantigens. We hypothesized that natural autoantibodies to SELENOP are prevalent in thyroid patients, impair Se transport, and negatively affect GPX3 biosynthesis. Using a newly established quantitative immunoassay, SELENOP autoantibodies were particularly prevalent in Hashimoto's thyroiditis as compared with healthy control subjects (6.6% versus 0.3%). Serum samples rich in SELENOP autoantibodies displayed relatively high total Se and SELENOP concentrations in comparison with autoantibody-negative samples ([Se]; 85.3 vs. 77.1 µg/L, p = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, p = 0.001), while GPX3 activity was low and correlated inversely to SELENOP autoantibody concentrations. In renal cells in culture, antibodies to SELENOP inhibited Se uptake. Our results indicate an impairment of SELENOP-dependent Se transport by natural SELENOP autoantibodies, suggesting that the characterization of health risk from Se deficiency may need to include autoimmunity to SELENOP as additional biomarker of Se status.
Asunto(s)
Autoanticuerpos/sangre , Enfermedad de Hashimoto/inmunología , Selenio/sangre , Selenoproteína P/inmunología , Adulto , Animales , Autoinmunidad , Femenino , Glutatión Peroxidasa/sangre , Glutatión Peroxidasa/metabolismo , Enfermedad de Hashimoto/sangre , Enfermedad de Hashimoto/metabolismo , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Neurodevelopmental diseases are often associated with other comorbidities, especially inflammatory processes. The disease may affect the trace element (TE) status, which in turn may affect disease severity and progression. Selenium (Se) is an essential TE required for the biosynthesis of selenoproteins including the transporter selenoprotein P (SELENOP) and extracellular glutathione peroxidase (GPX3). SELENOP deficiency in transgenic mice resulted in a Se status-dependent phenotype characterized by impaired growth and disturbed neuronal development, with epileptic seizures on a Se-deficient diet. Therefore, we hypothesized that Se and SELENOP deficiencies may be prevalent in paediatric patients with a neurodevelopmental disease. In an exploratory cross-sectional study, serum samples from children with neurodevelopmental diseases (n = 147) were analysed for total serum Se, copper (Cu), and zinc (Zn) concentrations as well as for the TE biomarkers SELENOP, ceruloplasmin (CP), and GPX3 activity. Children with epilepsy displayed elevated Cu and Zn concentrations but no dysregulation of serum Se status. Significantly reduced SELENOP concentrations were found in association with intellectual disability (mean ± SD (standard deviation); 3.9 ± 0.9 mg/L vs. 4.4 ± 1.2 mg/L, p = 0.015). A particularly low GPX3 activity (mean ± SD; 172.4 ± 36.5 vs. 192.6 ± 46.8 U/L, p = 0.012) was observed in phacomatoses. Autoantibodies to SELENOP, known to impair Se transport, were not detected in any of the children. In conclusion, there was no general association between Se deficiency and epilepsy in this observational analysis, which does not exclude its relevance to individual cases. Sufficiently high SELENOP concentrations seem to be of relevance to the support of normal mental development. Decreased GPX3 activity in phacomatoses may be relevant to the characteristic skin lesions and merits further analysis. Longitudinal studies are needed to determine whether the observed differences are relevant to disease progression and whether correcting a diagnosed TE deficiency may confer health benefits to affected children.
Asunto(s)
Síndromes Neurocutáneos , Selenio , Oligoelementos , Animales , Niño , Estudios Transversales , Glutatión Peroxidasa , Humanos , Ratones , Selenoproteína P , Selenoproteínas/genéticaRESUMEN
BACKGROUND: The synthesis of thyroid hormone depends on a set of trace elements, most importantly selenium and iodine. The dietary supply with certain micronutrients is limited in many areas of the world, including central Europe and large parts of Asia and Africa. Moreover, both thyroid disease risk and therapy effects are modulated by trace element supply and status. OBJECTIVE: Assessment of trace element status in thyroid patients in a European metropolis. MATERIAL AND METHODS: Adult patients visiting a medical praxis in Berlin, Germany, were enrolled into a cross-sectional analysis, and serum samples were obtained from thyroid patients (n = 323) with different conditions including goitre, hypothyroidism, malignancy or autoimmune thyroid disease. Trace elements (iodine, selenium, copper and zinc) were assessed by ICP-MS/MS or total reflection X-ray analysis, along with two protein biomarkers of selenium status (selenoprotein P, glutathione peroxidase), and compared to the clinical phenotype. RESULTS: The patients displayed relatively low serum zinc and selenium concentrations as compared to a set (n = 200) of healthy subjects (zinc; 1025+/-233 vs. 1068+/-230 µg/L, p < 0.01, selenium; 76.9+/18.8 vs. 85.1+/-17.4 µg/L, p < 0.0001). A high fraction of patients (37.5%) was classified as selenium-deficient (serum selenium concentrations <70 µg/L), in particular the patients with thyroid malignancy (59%). Serum copper was not different between the groups, and total serum iodine concentrations were unrelated to thyroid disease. Explorative statistical analyses yielded no significant interactions between the trace elements and disease parameters, except for free thyroxine inversely correlating to the copper/selenium ratio. CONCLUSIONS: In adult thyroid patients, there is no relation of circulating copper, iodine, selenium or zinc concentrations to thyroid hormone. However, a large fraction of German thyroid patients displays a considerable selenium deficit, known to constitute a disease risk potentially impairing convalescence and aggravating autoimmune disease processes. It appears advisable to testing thyroid patients for selenium deficiency, and once diagnosed, an increased supply via dietary counselling or active supplementation should be considered.