The ME Association End of Week Research Round-up | 10 April 2020

April 14, 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 3 – 9 April 2020

This week, 6 new research studies have been published, highlights include:

  • A UK study finding similarities in symptoms between ME/CFS and people with primary antibody deficiency (PAD).
  • Norwegian researchers found increased levels of MCP-1 in ME/CFS and fibromyalgia patients compared to healthy controls. MCP-1 stands for ‘Monocyte Chemoattractant Protein 1’ and it is a cytokine that attracts immune cells to sites of inflammation. It is implicated in autoimmune diseases, as well as neuroinflammatory disorders.
  • A study from the USA found that women with Golf War Illness, CFS and Fibromyalgia all have systemic hyperalgesia (heightened sensitivity to pain) compared to sedentary controls.

ME/CFS Research references and abstracts

1. Bansal RA et al. (2020)
The presence of overlapping quality of life symptoms in primary antibody deficiency (PAD) and chronic fatigue syndrome (CFS).
Allergy, Asthma & Clinical Immunology 16 (21).

Background: Fatigue, sleep disturbance and altered mood are frequently reported in patients with primary antibody deficiency syndrome (PADS) on adequate immunoglobulin replacement therapy. This study aimed to determine the frequency of symptoms compatible with chronic fatigue syndrome (CFS) in patients with PADS.

Methods: The study involved the distribution of 682 self-completed postal questionnaires to ascertain the presence and frequency of symptoms compatible with CFS in patients with PADS. The reporting of symptoms for each patient were scored against the CFS diagnostic criteria used within our own South London Chronic Fatigue service.

Results: The frequency of symptoms compatible with CFS were evident in 26 of the 188 patients (16.25%) returning adequately completed questionnaires. We considered a bias in the return of questionnaires amongst PADS patients with fatigue to be likely. As such we estimated the minimum frequency of CFS in patients with PADS to be 4% based on the 682 PAD patients to whom the questionnaire was distributed. This was significantly higher than the 0.5% estimate of the prevalence of CFS in the community in western populations. While the presence of significant fatigue correlated with the presence of anxiety and depression, there was no association with self-reported lung damage. Sleep disturbance affected 60% of the PAD patients returning satisfactory questionnaires and as expected the CFS score was higher in those with greater physical limitation.

Conclusions: We conclude that patients with PADS have a high frequency of fatigue, low mood and anxiety. We suggest routine questioning for the symptoms of fatigue, disturbed sleep and altered mood in patients with PADS. The use of several treatment strategies in CFS may prove beneficial in improving the quality of life of patients with PAD.

2. Groven N et al. (2020)
MCP-1 is Increased in Patients with CFS and FM, whilst several other immune markers are significantly lower than healthy controls.
Brain, Behaviour & Immunity- health [Epub ahead of print].

The role of the immune system in the pathogenesis of Fibromyalgia (FM) and Chronic fatigue syndrome (CFS) is not clear. We have previously reported increased levels of C-reactive protein (CRP) in these patient groups compared to healthy controls and wanted to further explore the levels of circulating immune markers in these populations.

The population consisted of three groups, 58 patients with FM, 49 with CFS and 54 healthy controls. All participants were females aged 18–60. Patients were recruited from a specialised university hospital clinic and controls were recruited by advertisement among the staff and students at the hospital and university. Plasma levels of Interferon (IFN)-γ, Interleukin (IL)-1β, IL-1ra, IL-4, IL-6, IL-8, IL-10, IL-17, Interferon gamma-induced protein (IP)-10, Monocyte Chemoattractant Protein (MCP)-1, Transforming Growth Factor (TGF)-β1, TGF-β2, TGF-β3 and Tumour Necrosis Factor (TNF)-α were analysed by multiplex. Differences between the three groups CFS, FM and controls, were analysed by Kruskal Wallis tests.

MCP-1 was significantly increased in both patient groups compared to healthy controls. IL-1β, Il-4, IL-6, TNF-α, TGF-β1, TGF-β2, TGF-β3, IL-10 and IL17 all were significantly lower in the patient groups than healthy controls. IFN-γ was significantly lower in the FM group. For IL-8, IL-10 and IL-1ra there were no significant difference when controlled for multiple testing.

In conclusion, in our material MCP-1 seems to be increased in patients both with CFS and with FM, while several other immune markers are significantly lower in patients than controls.

3. Loades ME et al. (2020)
Assessing functioning in adolescents with chronic fatigue syndrome: psychometric properties and factor structure of the School and Social Adjustment Scale and the Physical Functioning Subscale of the SF36.
Behavioural and Cognitive Psychotherapy [Epub ahead of print].

Background: Chronic fatigue syndrome (CFS) has a major impact on functioning. However, no validated measures of functioning for this population exist.

Aims: We aimed to establish the psychometric properties of the 5-item School and Social Adjustment Scale (SSAS) and the 10-item Physical Functioning Subscale of the SF-36 in adolescents with CFS.

Method: Measures were completed by adolescents with CFS (n = 121).

Results: For the Physical Functioning Subscale, a 2-factor solution provided a close fit to the data. Internal consistency was satisfactory. For the SSAS, a 1-factor solution provided an adequate fit to the data. The internal consistency was satisfactory. Inter-item and item-total correlations did not indicate any problematic items and functioning scores were moderately correlated with other measures of disability, providing evidence of construct validity.

Conclusion: Both measures were found to be reliable and valid and provide brief measures for assessing these important outcomes. The Physical Functioning Subscale can be used as two subscales in adolescents with CFS.

4. Sandler CX and Lloyd AR (2020)
Chronic fatigue syndrome: progress and possibilities.
The Medical Journal of Australia [Epub ahead of print].

Chronic fatigue syndrome (CFS) is a prevalent condition affecting about one in 100 patients attending primary care. There is no diagnostic test, validated biomarker, clear pathophysiology or curative treatment. The core symptom of fatigue affects both physical and cognitive activities, and features a prolonged post-activity exacerbation triggered by tasks previously achieved without difficulty. Although several different diagnostic criteria are proposed, for clinical purposes only three elements are required: recognition of the typical fatigue; history and physical examination to exclude other medical or psychiatric conditions which may explain the symptoms; and a restricted set of laboratory investigations.

Studies of the underlying pathophysiology clearly implicate a range of different acute infections as a trigger for onset in a significant minority of cases, but no other medical or psychological factor has been reproducibly implicated. There have been numerous small case-control studies seeking to identify the biological basis of the condition. These studies have largely resolved what the condition is not: ongoing infection, immunological disorder, endocrine disorder, primary sleep disorder, or simply attributable to a psychiatric condition.

A growing body of evidence suggests CFS arises from functional (non-structural) changes in the brain, but of uncertain character and location. Further functional neuroimaging studies are needed. There is clear evidence for a genetic contribution to CFS from family and twin studies, suggesting that a large scale genome-wide association study is warranted.

Despite the many unknowns in relation to CFS, there is significant room for improvement in provision of the diagnosis and supportive care. This may be facilitated via clinician education.

5. Surian A and Baraniuk A (2020)
Systemic Hyperalgesia in Females with Gulf War Illness, Chronic Fatigue Syndrome and Fibromyalgia.
Scientific Reports 10: 5751.

Pain is a diagnostic criterion for Gulf War Illness (GWI), Chronic Fatigue Syndrome (CFS), and fibromyalgia (FM). The physical sign of systemic hyperalgesia (tenderness) was assessed in 920 women who were stratified by 2000 Kansas GWI, 1994 CFS, and 1990 FM criteria. Pressure was applied by dolorimetry at 18 traditional tender points and the average pressure causing pain determined.

GWI women were the most tender (2.9 ± 1.6 kg, mean ± SD, n = 70), followed by CFS/FM (3.1 ± 1.4 kg, n = 196), FM (3.9 ± 1.4 kg, n = 56), and CFS (5.8 ± 2.1 kg, n = 170) compared to controls (7.2 ± 2.4 kg, significantly highest by Mann-Whitney tests p < 0.0001, n = 428). Receiver operating characteristics set pressure thresholds of 4.0 kg to define GWI and CFS/FM (specificity 0.85, sensitivities 0.80 and 0.83, respectively), 4.5 kg for FM, and 6.0 kg for CFS. Pain, fatigue, quality of life, and CFS symptoms were equivalent for GWI, CFS/FM and CFS. Dolorimetry correlated with symptoms in GWI but not CFS or FM.

Therefore, women with GWI, CFS and FM have systemic hyperalgesia compared to sedentary controls. The physical sign of tenderness may complement the symptoms of the Kansas criteria as a diagnostic criterion for GWI females, and aid in the diagnosis of CFS. Molecular mechanisms of systemic hyperalgesia may provide new insights into the neuropathology and treatments of these nociceptive, interoceptive and fatiguing illnesses.

6. Wirth K and Scheibenbogen C (2020)
A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors.
Autoimmune Reviews [Epub ahead of print].

Myalgic Encephalomyelitis or Chronic Fatigue Syndrome (CFS/ME) is a complex and severely disabling disease with a prevalence of 0.3% and no approved treatment and therefore a very high medical need. Following an infectious onset patients suffer from severe central and muscle fatigue, chronic pain, cognitive impairment, and immune and autonomic dysfunction. Although the etiology of CFS/ME is not solved yet, there is numerous evidence for an autoantibody mediated dysregulation of the immune and autonomic nervous system.

We found elevated ß2 adrenergic receptor (ß2AdR) and M3 acetylcholine receptor antibodies in a subset of CFS/ME patients. As both ß2AdR and M3 acetylcholine receptor are important vasodilators, we would expect their functional disturbance to result in vasoconstriction and hypoxemia. An impaired circulation and oxygen supply could result in many symptoms of ME/CFS. There are consistent reports of vascular dysfunction in ME/CFS. Muscular and cerebral hypoperfusion has been shown in ME/CFS in various studies and correlated with fatigue. Metabolic changes in ME/CFS are also in line with a concept of hypoxia and ischemia.

Here we try to develop a unifying working concept for the complex pathomechanism of ME/CFS based on the presence of dysfunctional autoantibodies against ß2AdR and M3 acetylcholine receptor and extrapolate it to the pathophysiology of ME/CFS without an autoimmune pathogenesis.

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