Research Digest 17/04/20

Welcome to the 45th Emerge Australia Research Digest, where you will find summaries of some of the latest research and information about ME/CFS, with links to the complete articles.

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Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS)

Authors: Lande, A., Fluge, Ø., Strand, E.B., Flåm, S.T., Sosa, D.D., Mella, O., Egeland, T., Saugstad, O.D., Lie, B.A. & Viken, M.K.

This Norwegian study aimed to investigate the possible role of autoimmunity in ME/CFS by examining Human Leukocyte Antigen (HLA) associations. HLA molecules play an essential role in our immune system, activating T cells, and HLA associations are known indicators of autoimmune disease. High-resolution HLA genotyping by next-generation sequencing was performed in 426 Norwegian ME/CFS (Canadian Consensus Criteria) patients and 4511 healthy controls. The sample included patients who were severe or very severe (12.5% of the sample). 

Two independent HLA associations were discovered, tagged by the alleles HLA-C*07:04 and HLA-DQB1*03:03. Respectively, 7.7% and 12.7% of the ME/CFS patient group carried these alleles. Overall, 19.2% of the ME/CFS patient group carried one or both alleles, compared to 12.2% in the control group.

The authors believe these new HLA association findings suggest the immune system does play a role in the pathogenesis of ME/CFS.

HERV-K and HERV-W transcriptional activity in myalgic encephalomyelitis/chronic fatigue syndrome

Authors: Rodrigues, L.S.,  da Silva Nali, L.H.,  Leal, C.O.D., Sabino, E.C., Lacerda, E.M., Kingdon, C.C., Nacul, L.,  Romano, C.M.

Human endogenous retroviruses (HERVs) are remnants of ancient viruses which have been incorporated into human DNA, making up approximately 8% of the human genome. There are more than 30 families of HERVs. While most HERVs are inactive, their capacity for molecular mimicry and immune dysregulation has led them to be considered as possible triggers for autoimmunity. 

The purpose of this study was to investigate the expression of two families of HERVs (K and W), in 100 ME/CFS patients (meeting Canadian Consensus criteria or Fukuda criteria or both) as well as 70 healthy controls. The patient group was subdivided into 75 patients with moderate symptoms (ambulatory) and 25 with severe symptoms (housebound or bedbound). The study used blood samples from the UK ME Biobank.

Overall, HERV-K and W expression was found in almost all participants, with just one healthy control and one patient with moderate symptoms having no HERV activity. There were no significant differences between the ME/CFS patients and healthy controls in HERV-W expression. However, the level of HERV-K expression was significantly greater in the moderate ME/CFS patients compared to the controls, with no differences between the moderate and severe ME/CFS groups.

The authors do not claim that there is a direct link between HERVs and ME/CFS, but propose this as new information that should be explored further.

A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors

Authors: Wirth, K., & Scheibenbogen, C.

In this publication, the authors attempt to explain the significance of elevated auto-antibodies against ß2-adrenergic receptors (ß2AdR) and M3 acetylcholine receptors, which have been found in a subset of ME/CFS patients, with a hypothesis that potentially explains the underlying mechanism of the condition.

The authors suggest that auto-antibodies against ß2AdR could cause ß2AdR dysfunction, which could in turn explain cardiovascular abnormalities commonly seen in ME/CFS such as low heart rate variability, high sympathetic and low vagal tone. The authors review the evidence for cardiovascular dysfunction, such as preload failure, autonomic aspects of the condition such as orthostatic intolerance, as well as the relatively high prevalence of craniocervical and atlantoaxial instability in ME/CFS patients, and suggest that ß2AdR dysfunction may be an important risk factor in the pathophysiology of ME/CFS. Dysfunctional autoantibodies to ß2AdR, polymorphisms and desensitisation of ß2AdR by high sympathetic tone, are discussed as potential causes of this dysregulation.

MCP-1 is Increased in Patients with CFS and FM, whilst several other immune markers are significantly lower than healthy controls

Author: Groven, N., Fors, E.A., Stunes, A.K., Reitan, S.K.

In this study, researchers examined circulating blood immune markers (inflammatory, anti-inflammatory, and regulatory) in ME/CFS and fibromyalgia. The study included 49 ME/CFS patients (Fukuda criteria), 58 fibromyalgia patients (1990 ACR criteria) and 54 healthy controls.  All participants were females between the ages of 18–60. 

Results showed that Monocyte Chemoattractant Protein (MCP)-1, a pro-inflammatory marker, was significantly higher in all patient groups compared with controls. For several other immune markers, both patient groups had lower levels than the controls. The authors noted that their results weren’t consistent with some previous studies, although they also acknowledged the overall inconsistency of results in immune studies in these conditions. A limitation of this study is that participants were not age-matched, and age-related associations were found, which may explain some of the inconsistencies with previous studies. 

Overall, this study highlights both the role of the immune system in these two conditions as well as the considerable overlap between them.

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