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

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.

Pressure Point Thresholds and ME/CFS Comorbidity as Indicators of Patient's Response to Manual Physiotherapy in Fibromyalgia.

Current pharmacological treatments of Fibromyalgia (FM) are merely symptom palliative, as clinical trials have so far failed to provide overall benefits without associated harms. Polypharmacy often leads to patient's health deterioration and chronic drug use to an eventual lack of patient's response. Emerging evidence supports that physiotherapy treatments based on mechanical triggers improve FM symptoms and therefore could be used for therapeutic purposes by themselves or in combination with current pharmacological treatments, as part of integrative medicine programs. However, a paucity of studies rigorously and systematically evaluating this possibility exists. This study uses scores from validated standardized questionnaires, algometer pressure point threshold (PPT) readings and responses from a custom self-developed questionnaire to determine the impact of a pressure-controlled custom manual protocol on FM hyperalgesia/allodynia, fatigue and patient's quality of life. The results show that patient's baseline sensitivity to pain inversely correlates with treatment response in FM. Moreover, post-stratification analysis unexpectedly reveals that patients presenting comorbid ME/CFS do not seem to respond to the applied therapy as those presenting FM only. Therefore, pre-treatment PPTs and ME/CFS comorbidity may serve as indicators to predict patient's response to physiotherapy programs based on mechanical triggers. Further exploration of these findings is granted. In addition, the study of gene expression profiles in the blood collection generated by this study should help unveil the molecular mechanisms behind patient's differential response to manual therapy.

Unraveling the Molecular Determinants of Manual Therapy: An Approach to Integrative Therapeutics for the Treatment of Fibromyalgia and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis.

Application of protocols without parameter standardization and appropriate controls has led manual therapy (MT) and other physiotherapy-based approaches to controversial outcomes. Thus, there is an urgency to carefully define standard protocols that elevate physiotherapy treatments to rigorous scientific demands. One way in which this can be achieved is by studying gene expression and physiological changes that associate to particular, parameter-controlled, treatments in animal models, and translating this knowledge to properly designed, objective, quantitatively-monitored clinical trials (CTs). Here, we propose a molecular physiotherapy approach (MPTA) requiring multidisciplinary teams, to uncover the scientific reasons behind the numerous reports that historically attribute health benefits to MT-treatments. The review focuses on the identification of MT-induced physiological and molecular responses that could be used for the treatment of fibromyalgia (FM) and chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). The systemic effects associated to mechanical-load responses are considered of particular relevance, as they suggest that defined, low-pain anatomic areas can be selected for MT treatment and yet yield overall benefits, an aspect that might result in it being essential to treat FM. Additionally, MT can provide muscle conditioning to sedentary patients without demanding strenuous physical effort, which is particularly detrimental for CFS/ME patients, placing MT as a real option for integrative medicine programs to improve FM and CFS/ME.