TGI Friday! Our weekly round-up of recently published research abstracts | 22 February 2013
From Clinical Infectious Diseases, 13 February 2013 [Epub ahead of print].
Human Endogenous Retrovirus-K18 Superantigen Expression and Human Herpesvirus-6 and Human Herpesvirus-7 Viral Loads in Chronic Fatigue Patients.
Oakes B, Hoagland-Henefield M, Komaroff AL, Erickson JL, Huber BT.
Graduate Program in Pharmacology and Experimental Therapeutics, Sackler School of Graduate Biomedical Sciences, Tufts University.
BACKGROUND.
Chronic Fatigue Syndrome (CFS) is a complex, heterogeneous disease characterized by debilitating fatigue that is not improved with bed rest and worsens after physical activity or mental exertion. Despite
extensive research into a cause of CFS, no definitive etiology has been determined; however, a large percentage of CFS patients note an acute infectious event that triggers their fatigue.
Blood and saliva were collected from 39 CFS cases and 9 healthy control subjects. Peripheral blood mononuclear cells (PBMCs) were tested for human endogenous retrovirus-K18 (HERV-K18) env transcripts using a TaqMan qPCR. In addition, viral copy number of human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) were measured in both saliva and PBMCs using TaqMan qPCRs. Transcript levels and viral copy number were compared to patient CFS symptom severity.
HERV-K18 env transcripts were not significantly different between healthy control subjects and CFS patients.
Also, HERV-K18 env transcripts did not correlate with HHV-6 viral copy number or HHV-7 viral copy number in either PBMCs or saliva. HHV-6 viral copy number and HHV-7 viral copy number in both PBMCs and saliva were not significantly different between healthy control subjects and CFS patients.
HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number did not correlate with CFS symptom severity.
We fail to demonstrate a difference in HERV-K18 env transcripts, HHV-6 viral copy number, and HHV-7 viral copy number between CFS patients and healthy controls. Our data do not support the hypothesis of reactivation of HHV-6 or HHV-7 in CFS.
From In Vivo March-April 2013 vol. 27 no. 2 177-187. Full text: http://iv.iiarjournals.org/content/27/2/177.full
Plasmacytoid Dendritic Cells in the Duodenum of Individuals Diagnosed with Myalgic Encephalomyelitis Are Uniquely Immunoreactive to Antibodies to Human Endogenous Retroviral Proteins
KENNY L. DE MEIRLEIR(3*), SVETLANA F. KHAIBOULLINA(1*), MARC FRÉMONT(4), JAN HULSTAERT(5), ALBERT A. RIZVANOV(6) ANDRÁS PALOTÁS(7) and VINCENT C. LOMBARDI(1,2)
(1) Whittemore Peterson Institute for Neuro-Immune Disease, Reno, NV, U.S.A.;
(2) Department of Pathology, University of Nevada, Reno, NV, U.S.A.;
(3) Department of Human Physiology and Medicine, Vrije University of Brussels, Brussels, Belgium;
(4) R.E.D. Laboratories, Zellik, Belgium;
(5) Department of Gastroenterology, General Hospital Jan Portaels, Vilvoorde, Belgium;
(6) Department of Genetics, Kazan Federal University, Kazan, Russia;
(7) Asklepios-Med (private medical practice and research center), Szeged, Hungary
Myalgic encephalomyelitis (ME) is a debilitating illness of unknown etiology characterized by neurocognitive dysfunction, inflammation, immune abnormalities and gastrointestinal distress. An increasing body of evidence suggests that disruptions in the gut may contribute to the induction of neuroinflammation. Therefore, reports of human endogenous retroviral (HERV) expression in association with neuroinflammatory diseases prompted us to investigate the gut of individuals with ME for the presence of HERV proteins. In eight out of 12 individuals with ME, immunoreactivity to HERV proteins was observed in duodenal biopsies.
In contrast, no immunoreactivity was detected in any of the eight controls. Immunoreactivity to HERV Gag and Env proteins was uniquely co-localized in hematopoietic cells expressing the C-type lectin receptor CLEC4C (CD303/BDCA2), the costimulatory marker CD86 and the class II major histocompatibility complex HLA-DR, consistent with plasmacytoid dendritic cells (pDCs). Although the significance of HERVs present in the pDCs of individuals with ME has yet to be determined, these data raise the possibility of an involvment of pDCs and HERVs in ME pathology. To our knowledge, this report describes the first direct association between pDCs and HERVs in human disease.
Journal of Psychiatric Research, 16 February 2013
The prevalence and impact of early childhood trauma in Chronic Fatigue Syndrome.
Kempke S, Luyten P, Claes S, Van Wambeke P, Bekaert P, Goossens L, Van Houdenhove B.
Department of Psychology, University of Leuven, Leuven, Belgium.
Although some studies have found high rates of early childhood trauma in Chronic Fatigue Syndrome (CFS), the role of early trauma in this condition remains controversial.
This study examined the prevalence of early childhood trauma and its impact on daily fatigue and pain levels over a 14-day period in a sample of 90 carefully screened CFS patients using a diary method approach. Data were analyzed using multilevel analysis.
More than half of the patients (54.4%) had experienced at least one type of early trauma, with the majority of these patients reporting multiple traumas. Prevalence rates were particularly high for emotional trauma (i.e., emotional abuse and/or emotional neglect) (46.7%). Moreover, total trauma scores and emotional abuse significantly predicted higher levels of daily fatigue and pain over the 14-day period, even when controlling for demographic features and depressed mood.
This is the first study to demonstrate that early childhood trauma predicts increasing levels of core symptoms of CFS in the daily flow of life. Moreover, findings of this study suggest that emotional trauma may be particularly important in CFS.
From BioPsychosocial Medicine, 7 February 2013.
Relationship between autonomic cardiovascular control, case definition, clinical symptoms, and functional disability in adolescent chronic fatigue syndrome: an exploratory study
Vegard B Wyller(1,2*) and Ingrid B Helland(2)
(1) Department of Paediatrics, Oslo University Hospital and University of Oslo, Oslo, Norway
(2) Department of Paediatrics, Oslo University Hospital Rikshospitalet, N-0027, Oslo, Norway
Chronic Fatigue Syndrome (CFS) is characterized by severe impairment and multiple symptoms. Autonomic dysregulation has been demonstrated in several studies.
We aimed at exploring the relationship between indices of autonomic cardiovascular control, the case definition from Centers for Disease Control and Prevention (CDC criteria), important clinical symptoms, and disability in adolescent chronic fatigue syndrome.
38 CFS patients aged 12–18 years were recruited according to a wide case definition (ie. not requiring accompanying symptoms) and subjected to head-up tilt test (HUT) and a questionnaire. The relationships between variables were explored with multiple linear regression analyses. In the final models, disability was positively associated with symptoms of cognitive impairments (p<0.001), hypersensitivity (p<0.001), fatigue (p=0.003) and age (p=0.007). Symptoms of cognitive impairments were associated with age (p=0.002), heart rate (HR) at baseline (p=0.01), and HR response during HUT (p=0.02). Hypersensitivity was associated with HR response during HUT (p=0.001), high-frequency variability of heart rate (HF-RRI) at baseline (p=0.05), and adherence to the CDC criteria (p=0.005). Fatigue was associated with gender (p=0.007) and adherence to the CDC criteria (p=0.04). In conclusion, a) The disability of CFS patients is not only related to fatigue but to other symptoms as well; b) Altered cardiovascular autonomic control is associated with certain symptoms; c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity.
2 thoughts on "TGI Friday! Our weekly round-up of recently published research abstracts | 22 February 2013"
From the last study "c) The CDC criteria are poorly associated with disability, symptoms, and indices of altered autonomic nervous activity."
Does this mean that the CDC criteria are too broad, or that those ME patients who least fitted the CDC criteria were more likely to have the ANS & other disabling symptoms?
Not quite sure.
JoT
We should know by now that just because someone is given a label of suffereing from ME it does not mean that they do actually have ME.
Neither of the HERV papers give an indication of what may be occurring in the neuroimmune disease ME, as both studies were based on the Fukuda CFS criteria.
Combining Fukuda CFS with the Canadian criteria produces a cohort of Fukuda CFS patients, not Canadian. Combing criteria means to use only what is common to both. So using both the Fukuda and Canadian criteria's select exactly the same patients, which are Fukuda. The Canadian criteria also remain subjective and have not been shown to identify people with a neuroimmune disease. Using the entry criteria they have, no one knows what these separate groups of patients were suffering from. In the De Meirleir study we do know they were experiencing GI distress and the biopsy revealed empirical evidence of inflammation, which would be enough to transactivate HERV expression.
HERVs are ancient retroviruses that are present in all humans. HERV's make up 8% of the human genome.
One would not expect HERV-K to be expressed in ME patients, because HERV-K is not expressed preferentially in any neurorological disease.
The HERV commonly expressed in Multiple Sclerosis is HERV-W, which is alternatively known as the multiple sclerosis retrovirus. HERV-W is a gammaretroviral HERV.
HERV proteins are found in any infection or when even small amounts of inflammation is present, as with the de Meirleir paper.
The antibody used in the De Meirleir study only reacts with a particular protein conformation. Why didn't the WPI name the HERV? HERV proteins are not associated with autoimmunity. The human body does not raise antibodies against HERV proteins. This would not explain the serology results in the Dr Mikovits Dr Ruscetti study, as antibodies to retroviral proteins were found in the blood.