The ME Association End of Week Research Round-up | 13 March 2020


Charlotte Stephens, Research Correspondent, ME Association.

We show below brief summaries of the research studies about ME/CFS that have been published in the last week, followed by the abstracts from those studies.

This information will be included in the monthly update to the central Research Index which is made freely available as a download at the end of every month.

You can also find the Index in the Research section of the website together with a list of Research Summaries from the ME Association that provide lay explanations of the more important and interesting work that has been published to date.

ME/CFS Research Published 7th – 13th March 2020

This week, 3 new research studies have been published:

1. Researchers from Bulgaria were looking at the prevalence of three different viruses in 58 ME/CFS patients compared to 50 controls: Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6). They also looked at whether the viruses were active or latent.

Plasma levels (showing latent infection) of all three viruses were slightly higher in ME/CFS patients compared to controls. No active CMV or HHV-6 infections were observed. Of most interest, active EBV infection was found to be significantly higher in the ME/CFS group compared to controls.

“In conclusion, our study… showed high rate of active EBV infection among ME/CFS patients indicating that at least in a subset of cases EBV is important factor for development of disease.”

2. Researchers from Norway have proposed that having an altered microbiome and IBS can increase the risk of developing ME/CFS.

Furthermore, they found a strong correlation between antibiotic use in early childhood and IBS. Out of the 1100 IBS patients seen over a 9-year period, 80%–90% developed joint/muscle pain and chronic fatigue, and 65% were diagnosed with ME. 

The researchers conclude: “Our hypothesis is that “the dysbiotic march” begins with antibiotic-induced “missing microbes”, via abdominal discomfort, food intolerance and IBS, then years later, joint/muscle pain and chronic fatigue may develop and ultimately progress to ME. The progress of the disease, i.e. the march from IBS to ME, may well be due to new microbes or other infectious agents invading and conquering the biofilm to exploit its growth conditions.”

3. A study from Berlin found that people with ME/CFS have higher occurrence of Endothelial dysfunction (ED).

Endothelial dysfunction is where there is abnormal functioning of the endothelial cells lining blood vessels, which leads to a reduced vasodilative response to lack of oxygen or a build-up of waste products in the blood.

The researchers measured endothelial function in 35 patients and 20 healthy controls. Endothelial dysfunction was found in 51% of patients, compared to 20% of controls. Furthermore, epithelial dysfunction correlated with disease severity- those that had it reported more severe symptoms.

ED is found in various conditions including diabetes mellitus, arterial hypertension, chronic heart failure, and stroke. There is growing evidence that ED is frequent in autoimmune disease and is associated with chronic inflammation.

The authors conclude: “Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.”

ME/CFS Research references and abstracts

1. Berstad A et al. (2020)
From IBS to ME- The dysbiotic march hypothesis
Medical Hypothesis 140, 109648.

Abstract
Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown.

Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”.

In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age.

Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.

2. Scherbakov N et al. (2020)
Peripheral endothelial dysfunction in myalgic encephalomyelitis/chronic fatigue syndrome
ESC Heart Failure [Epub ahead of print].

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystem disease. Evidence for disturbed vascular regulation comes from various studies showing cerebral hypoperfusion and orthostatic intolerance.

The peripheral endothelial dysfunction (ED) has not been sufficiently investigated in patients with ME/CFS. The aim of the present study was to examine peripheral endothelial function in patients with ME/CFS.

Thirty-five patients [median age 40 (range 18-70) years, mean body mass index 23.8 ± 4.2 kg/m2 , 31% male] with ME/CFS were studied for peripheral endothelial function assessed by peripheral arterial tonometry (EndoPAT2000). Clinical diagnosis of ME/CFS was based on Canadian Criteria.

Nine of these patients with elevated antibodies against β2-adrenergic receptor underwent immunoadsorption, and endothelial function was measured at baseline and 3, 6, and 12 months follow-up. ED was defined by reactive hyperaemia index ≤1.81.

Twenty healthy subjects of similar age and body mass index were used as a control group. Peripheral ED was found in 18 of 35 patients (51%) with ME/CFS and in 4 healthy subjects (20%, P < 0.05).

Patients with ED, in contrast to patients with normal endothelial function, reported more severe disease according to Bell score (31 ± 12 vs. 40 ± 16, P = 0.04), as well as more severe fatigue-related symptoms (8.62 ± 0.87 vs. 7.75 ± 1.40, P = 0.04) including a higher demand for breaks [9.0 (interquartile range 7.0-10.0) vs. 7.5 (interquartile range 6.0-9.25), P = 0.04].

Peripheral ED showed correlations with more severe immune-associated symptoms (r = -0.41, P = 0.026), such as sore throat (r = -0.38, P = 0.038) and painful lymph nodes (r = -0.37, P = 0.042), as well as more severe disease according to Bell score (r = 0.41, P = 0.008) and symptom score (r = -0.59, P = 0.005).

There were no differences between the patient group with ED and the patient group with normal endothelial function regarding demographic, metabolic, and laboratory parameters. Further, there was no difference in soluble vascular cell adhesion molecule and soluble intercellular adhesion molecule levels.

At baseline, peripheral ED was observed in six patients who underwent immunoadsorption. After 12 months, endothelial function had improved in five of these six patients (reactive hyperaemia index 1.58 ± 0.15 vs. 2.02 ± 0.46, P = 0.06).

Peripheral ED is frequent in patients with ME/CFS and associated with disease severity and severity of immune symptoms. As ED is a risk factor for cardiovascular disease, it is important to elucidate if peripheral ED is associated with increased cardiovascular morbidity and mortality in ME/CFS.

3. Shikova et al. (2020)
Cytomegalovirus, Epstein-Barr Virus and Human Herpesvirus 6 Infections in Patients with Myalgic Еncephalomyelitis/Chronic Fatigue Syndrome
Journal of Medical Virology [Epub ahead of pint].

Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem chronic disease. The etiology and pathogenesis of ME/CFS are unknown. Infections of cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesvirus-6 (HHV-6) are suspected as etiological agents for ME/CFS.

This study aims to estimate prevalence and type (active/latent) of EBV, CMV and HHV-6 infections in Bulgarian ME/CFS patients. In the study were included 58 ME/CFS patients and 50 healthy controls. Virus-specific antibodies were detected by ELISA and viral genomic sequences in PBMCs and plasma samples – by nPCR.

We did not observe any significant differences in virus specific IgG and IgM positivity rates between ME/CFS patients and control group. In ME/CFS plasma samples EBV DNA was found in 24.1%, CMV DNA – in 3.4% and HHV-6 DNA in 1.7% of samples. EBV DNA was detected in 4%, CMV and HHV-6 DNA were not found in plasma samples of controls. The frequency of viral genome detection in PBMCs of patients and controls was 74% vs 78% for CMV, 81% vs 84% for EBV, and 82.8% vs 82% for HHV-6. The difference in frequency of EBV active infection in ME/CFS and control group was statistically significant (p=0.0027). No ME/CFS and control individuals with active CMV and HHV-6 infection were observed.

In conclusion, our study using both serological and PCR-based techniques for distinguishing between active and latent infection, showed high rate of active EBV infection among ME/CFS patients indicating that at least in a subset of cases EBV is important factor for development of disease.

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