Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone.

Abstract

Chronic Fatigue Syndrome (CFS) presents with symptoms of hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety.  However, thyroid hormone (TH) profiles of elevated thyrotropin and low thyroxine  (T4) are not consistently observed. Recently, autoantibodies to the Se transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto's thyroiditis  and shown to impair selenoprotein expression. We hypothesized that SELENOP-aAb  are prevalent in CFS, and associate with reduced selenoprotein expression and impaired TH deiodination. Se status and SELENOP-aAb prevalence was compared by  combining European CFS patients (n = 167) and healthy controls (n = 545) from  different sources. The biomarkers total Se, glutathione peroxidase (GPx3) and  SELENOP showed linear correlations across the samples without reaching  saturation, indicative of Se deficiency. SELENOP-aAb prevalence was 9.6-15.6% in  CFS versus 0.9-2.0% in controls, depending on cut-off for positivity. The linear  correlation between Se and GPx3 activity was absent in SELENOP-aAb positive  patients, suggesting impaired Se supply of kidney. A subgroup of paired control  (n = 119) and CSF (n = 111) patients had been characterized for TH and  biochemical parameters before. Within this subgroup, SELENOP-aAb positive  patients displayed particularly low deiodinase activity (SPINA-GD index), free T3  levels, total T3 to total T4 (TT3/TT4) and free T3 to free T4 (FT3/FT4) ratios.  In 24 h urine, iodine concentrations were significantly lower in SELENOP-aAb  positive than in SELENOP-aAb negative patients or controls (median (IQR); 43.2  (16.0) vs. 58.9 (45.2) vs. 89.0 (54.9) μg/L). The data indicate that SELENOP-aAb  associate with low deiodination rate and reduced activation of TH to active T3. We conclude that a subset of CFS patients express SELENOP-aAb that disturb Se  transport and reduce selenoprotein expression in target tissues. Hereby, TH  activation decreases as an acquired condition not reflected by thyrotropin and T4  in blood. This hypothesis opens new diagnostic and therapeutic options for  SELENOP-aAb positive CFS, but requires clinical evidence from intervention  trials.