Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis

• Published in: International journal of molecular sciences 2021-12, Vol.22 (23), p.13088
• Main Authors: Sun, Qian, Mehl, Sebastian, Renko, Kostja, Seemann, Petra, Görlich, Christian L, Hackler, Julian, Minich, Waldemar B, Kahaly, George J, Schomburg, Lutz
• Format: Article
• Language: English
• Subjects: Adult; Animals; antioxidative defense; Autoantibodies; Autoantibodies - blood; autoantibody; Autoantigens; Autoimmune diseases; Autoimmunity; Biomarkers; Biosynthesis; Cell culture; Female; Gene expression; Glutathione peroxidase; Glutathione Peroxidase - blood; Glutathione Peroxidase - metabolism; Hashimoto Disease - blood; Hashimoto Disease - immunology; Hashimoto Disease - metabolism; Hashimoto’s thyroiditis; Hepatocytes; Human subjects; Humans; Hypotheses; Immunoassay; Inflammation; Male; Middle Aged; Peroxidase; Proteins; Risk analysis; Risk factors; Selenium - blood; Selenocysteine; Selenoprotein P - immunology; Selenoproteins; Thyroid diseases; Thyroiditis; trace element; Trace elements; Transgenic mice
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222313088

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, = 0.0178, and [SELENOP]; 5.1 vs. 3.5 mg/L, = 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.