Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis

Abstract:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a chronic multisystem disease characterized by a variety of symptoms, and exhibits various features of an autoimmune-like disease. Subtypes are well recognized but to date are difficult to identify objectively. The disease may be triggered by infection with a variety of micro-organisms, including Epstein-Barr virus (EBV).

A subset of CFS/ME patients exhibit up regulation of EBV virus induced gene 2 (EBI2) mRNA in peripheral blood mononuclear cells (PBMC), and these patients appear to have a more severe disease phenotype and lower levels of EBNA1 IgG. EBI2 is induced by EBV infection and has been found to be upregulated in a variety of autoimmune diseases. EBI2 is a critical gene in immunity and central nervous system function; it is a negative regulator of the innate immune response in monocytes. Its heterogeneous expression in CFS/ME could explain the variable occurrence of a variety of immune and neurological abnormalities which are encountered in patients with CFS/ME.

The EBI2 subtype occurred in 38-55% CFS/ME patients in our studies. Further work is required to confirm the role of EBV and of EBI2 and its oxysterol ligands in CFS/ME, and to identify the most practical means to identify patients of the EBI subtype. There are two EBI2 antagonists currently in development, and these may hold promise in the treatment of CFS/ME patients of the EBI subtype.

Source: Kerr JR. Epstein-Barr Virus Induced Gene-2 Upregulation Identifies a Particular Subtype of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Front Pediatr. 2019 Mar 13;7:59. doi: 10.3389/fped.2019.00059. eCollection 2019. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424879/ (Full article)

Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

AIM: To identify subtypes in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) based on DNA methylation profiles and health scores.

METHODS: DNA methylome profiles in immune cells were integrated with symptomatology from 70 women with ME/CFS using similarity network fusion to identify subtypes.

RESULTS: We discovered four ME/CFS subtypes associated with DNA methylation modifications in 1939 CpG sites, three RAND-36 categories and five DePaul Symptom Questionnaire measures. Methylation patterns of immune response genes and differences in physical functioning and postexertional malaise differentiated the subtypes.

CONCLUSION: ME/CFS subtypes are associated with specific DNA methylation differences and health symptomatology and provide additional evidence of the potential relevance of metabolic and immune differences in ME/CFS with respect to specific symptoms.

Source: de Vega WC, Erdman L, Vernon SD, Goldenberg A, McGowan PO. Integration of DNA methylation & health scores identifies subtypes in myalgic encephalomyelitis/chronic fatigue syndrome. Epigenomics. 2018 Apr 25. doi: 10.2217/epi-2017-0150. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29692205

Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness

Abstract:
Past research has subtyped patients with Myalgic Encephalolyelitis (ME) and Chronic Fatigue Syndrome (CFS) according to factors related to illness onset, illness duration, and age. However, no classification system fully accounts for the wide range of symptom severity, functional disability, progression, and prognosis seen among patients. This study examined whether illness trajectories among individuals with CFS were predictive of different levels of symptomology, functional disability, and energy expenditure.
Of the participants (N=541), the majority described their illness as Fluctuating (59.7%), with 15.9% Constantly Getting Worse, 14.1% Persisting, 8.5% Relapsing and Remitting, and 1.9% Constantly Getting Better. The illness courses were associated with significant differences in symptomology on select domains of the DSQ, functioning on select subscales of the SF-36, and on overall levels of energy expenditure.
The significant symptomatic and functional differences between groups suggest that subtyping patients with CFS according to illness course is a promising method for creating more homogeneous groups of patients.
Source:  Jamie Stoothoff, Kristen Gleason, Stephanie McManimen, Taylor Thorpe and Leonard A. Jason.  Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness. Symbiosis, June 26, 2017. https://symbiosisonlinepublishing.com/biosensors-biomarkers-diagnostics/biosensors-biomarkers-diagnostics13.pdf (Full article)

A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis

Abstract:

Outbreaks of illnesses of unknown etiology typified by a chronic relapsing course of constitutional symptoms and nervous system involvement have collectively been referred to as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. To examine heterogeneity of clinical presentation, a comparative review was undertaken for 12 well-documented outbreaks reported since 1934.

A systemic syndrome characterized by excessive fatigue, myalgias, headache, low-grade fever, and other constitutional symptoms was common to cases in all outbreaks. However, marked heterogeneity in the range of neurological features was apparent.

On the basis of predominant neurological manifestations, outbreaks could be grouped into four levels of increasing neurological involvement: affective neuropsychological changes (level I); prominent cutaneous sensory symptoms with both affective and cognitive neuropsychological changes (level II); marked objective paresis with cutaneous sensory as well as affective and cognitive neuropsychological changes (level III); and cutaneous sensory, affective and cognitive neuropsychological, posterior column, cranial nerve, and mixed upper and lower motor neuron changes (level IV). Groups with the most prominent objective neurological findings (levels III and IV) comprised exclusively outbreaks reported between the 1930s and 1950s. All but one outbreak in groups with less prominent neurological findings (levels I and II) were reported between the 1960s and 1980s; a range of neurological features was observed for these groups.

Because a complete neurological examination is not emphasized as part of the diagnostic workup in current outbreaks, it is possible that less obvious neurological findings may be overlooked. Careful evaluation of neurological features in epidemic and endemic cases of what is now called chronic fatigue syndrome may be one approach to distinguishing subtypes of what has been described in the past as a nosological entity.

 

Source: Briggs NC, Levine PH. A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. Clin Infect Dis. 1994 Jan;18 Suppl 1:S32-42. http://www.ncbi.nlm.nih.gov/pubmed/8148451