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

Abstract

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.

Autoimmunity to selenoprotein P predicts breast cancer recurrence

“…Natural SELENOP-aAb in the serum samples were detected and assessed as described recently [ 21 ]. Briefly, serum samples were incubated with a fusion protein consisting of a secreted alkaline phosphatase (SEAP) fused in frame to recombinant SELENOP variant in which selenocysteine has been replaced by cysteine residues as reporter (SEAP-SELENOP, selenOmed GmbH).…”

“…All three biomarkers were inversely associated with prognosis. Besides these interrelated biomarkers of Se status, natural autoantibodies to SELENOP (SELENOP-aAb) have recently been reported in healthy subjects and thyroid patients, obviously capable of interfering with regular Se transport by SELENOP [ 21 ].…”

Autoimmunity to the Follicle-Stimulating Hormone Receptor (FSHR) and Luteinizing Hormone Receptor (LHR) in Polycystic Ovarian Syndrome

“…Notable limitations include the lack of characterization of the FSHR-aAb assay by a commonly available antiserum (for our unsuccessful attempts to identify a suitable commercial product), the nature of the assays relying solely on binding without providing information on the potential biological activity of the aAb as agonistic, antagonistic, or merely neutral, and the lack of clinical information on the control samples other than sex, age and personal assessment as healthy. Moreover, only few positive samples were identified, and no consistent correlation to a relevant clinical parameter was observed due to the low frequency of positivity, rendering it impossible to determine relevant cut-offs for the binding index as measure of autoantibody concentrations in contrast to other similar studies [57]. Especially in view that the diagnosis of PCOS is difficult and often takes years to be done [58], we can moreover not exclude that the positive samples identified in the control cohort are just un-diagnosed cases of PCOS or display other signs of subfertility.…”

Selenium Metabolism and Biosynthesis of Selenoproteins in the Human Body

“…Recently, it was found that some thyroiditis patients had pathogenic anti-SELENOP autoantibodies that negatively affect Se transport and thereby inhibit the activity of some selenoproteins [ 109 ].…”