Preprint Autoantibodies to Selenoprotein P in Patients with CFS suggest Selenium Transport Impairment and .. Resistance to Thyroid Hormone, 2023, Qian Sun et a

Preprint, not peer reviewed : https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4332223

Autoantibodies to Selenoprotein P in Patients with Chronic Fatigue Syndrome suggest Selenium Transport Impairment and Acquired Resistance to Thyroid Hormone

Qian Sun1,2,†, Elisa Oltra3,†, D. A. Janneke Dijck-Brouwer4,†, Thilo Samson Chillon1,†,
Petra Seemann2, Sabrina Asaad1, Kamil Demircan1, José Andrés Espejo-Oltra3,
Teresa Sánchez-Fito3, Eva Martín-Martínez5, Waldemar B Minich1, Frits A. J. Muskiet4,
Lutz Schomburg1,*

Highlights
 Comprehensive analysis of Se and thyroid hormone in chronic fatigue syndrome
 Biomarkers of Se status, i.e., total Se, GPx3 and SELENOP correlate linearly
 Autoantibodies to SELENOP are relatively frequent in chronic fatigue syndrome
 SELENOP-aAb are associated with dysregulated GPx3 and DIO activities
 Strongly reduced urinary iodine reflects DIO suppression by SELENOP-aA

Abstract
Chronic Fatigue Syndrome (CFS) presents with symptoms similar to hypothyroidism, including mental and physical fatigue, poor sleep, depression, and anxiety. However, the typical thyroid hormone (TH) profile of elevated thyrotropin (TSH) and low thyroxine (T4) is not observed. Recently, autoantibodies to the selenium transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto’s thyroiditis and shown to impair selenium transport and selenoprotein expression.

We hypothesized that SELENOP-aAb are prevalent in CFS and impair TH metabolism.Selenium status in CFS (n=167) was compared to that of healthy controls (n=545). Two additional small groups were included, namely patients with fibromyalgia (FM; n=39), a disease often comorbid with CFS, and patients with post-COVID condition (n=24).

The serum/plasma Se biomarkers total Se, glutathione peroxidase (GPx3) and SELENOP levels showed linear correlations without reaching saturation, indicative of Se deficiency. TSH and total T4 levels fitted within normal ranges, but relative total T3 (%TT3) was low, and relative rT3 (%rT3) was elevated in CFS. SELENOP-aAb prevalence was 9.6-15.6% in CFS versus 0.9-2.0% in controls, depending on cut-off for positivity. An impairment of Se transport in SELENOP-aAb positive CFS patients is suggested by the lack of correlation between total Se and GPx3 activity. The same patients present with disturbed TH parameters, including low deiodinase (DIO) activity (SPINA-GD index) and particularly low urinary iodine as compared to controls (43.2 (16.0) vs. 89.0 (54.9) µg/L, P<0.001), indicating that SELENOP-aAb affect TH deiodination and iodine excretion.

We conclude that a considerable subset of CFS patients express SELENOP-aAb that disturb Se transport and cause low GPx3 and DIO activities. Hereby, TH deiodination decreases as an acquired condition that is not readily reflected by TSH or T4 in blood. This hypothesis opens new explanations and therapeutic options for SELENOP-aAb positive CFS and, perhaps, post-COVID condition patients, but requires additional clinical evidence from intervention trials.

 

Reminds me of this long PR thread


High-Dose Selenium Significantly Improves My Fatigue and Brain Fog

https://forums.phoenixrising.me/thr...ntly-improves-my-fatigue-and-brain-fog.27401/

 

This seems to be an interesting European collaboration between the German startup selenOmed, which is a spin off from the Charité hospital founded in 2017 and focuses on selenoprotein P, Prof Carmen Scheibenbogen’s team at Charité Berlin, Prof Elisa Oltra’s at the university of Valencia and two researchers at the university of Groningen.

However, it reminds me of CellTrend’s assay for autoantibodies against G-coupled protein receptors which turned out to be a fluke (at least for POTS). I do not know if the presence of autoantibodies against selenoprotein P is indicative of a disease.

https://selenomed.com/

 

This seems to be the main idea:

"Recently, autoantibodies to the selenium transporter SELENOP (SELENOP-aAb) have been identified in Hashimoto’s thyroiditis and shown to impair selenium transport and selenoprotein expression. [...] we tested the hypothesis that SELENOP-aAb are prevalent in patients with CFS, potentially causing impaired DIO expression and hypothyroidism that is not readily detectable by regular laboratory analyses of the classic biomarkers of the TH axis in blood."​

These seem to be the main results:



Depending on the cut-off used, CFS patients had more patients with a high amount of autoantibodies to the selenium transporter (9.6% - 15.6%) compared to controls (0.9-2%) and patients with fibromyalgia and Long Covid (where none of the patients was above the threshold).

From the text it is not clear if the determination of SELENOP-aAb was done blinded.

 

Here's the new pre-proof version: https://www.sciencedirect.com/science/article/pii/S2213231723001970.

Are we sure Scheibenbogen's team is connected, I can't see any connection?

Patients were recruited from the Parkstad Clinic in Amsterdam, what is this? I can only find a dermatologist with such a name. I hope someone knows more, I'm naturally always a bit sceptical if patients are recruited from somewhere in the Netherlands instead of just accessing some of Scheibenbogen's samples which seems so obvious.

 

Now published, open access here, https://www.sciencedirect.com/science/article/pii/S2213231723001970

 

Back to the old question -

• Rituximab didn't work so ME/CFS is not an autoimmune disease; versus
• there could be long lived plasma cells which wouldn't be killed by Rituximab still producing autoatibody?

 

Noticed that Cort [Health Rising*] has just published an article on this [Mar 27, 2024] & Fereshteh Jahanbani has just posted this -
"I love this topic, and I would like to introduce the term I have been using for it in the past few years: "Thyroid Hormone Resistance and Desensitization of Thyroid Receptors"!
This explains why some people have normal levels of TSH, T3, and T4 in the blood but still suffer from symptoms of hypothyroidism."
[https://www.facebook.com/fereshteh....417041&notif_t=close_friend_comment&ref=notif]

I've posted this comment - I'll keep you updated re any response -
"Interesting Fereshteh Jahanbani what do you suggest needs to be monitored i.e. if the standard tests don't work?"

*
https://www.healthrising.org/blog/2...E-YhTCevxCVEaNaKS3cqzWJ6_zEJD8NGQJwHFzkMgI3pZ

 

Wondering if this could e.g. result in a signal in GWAS [common variants - low to modest effects] and/or rare variant genetic study (whole genome sequences - higher impact variants)?