|
2010
 Detection
of MLV-related virus gene sequences in blood of patients with
chronic fatigue syndrome and healthy blood donors.
Shyh-Ching Lo, Natalia Pripuzova, Bingjie Li, Anthony L.
Komaroff, Guo-Chiuan Hung, Richard Wangc, and Harvey J. Alter
"...our results clearly support the central argument by Lombardi
et al. that MLV-related viruses are associated with CFS and are
present in some blood donors." "The possibility that these
agents might be blood-transmitted and pathogenic in blood
recipients warrants extensive research investigations of
appropriately linked donor–recipient cohorts."
2009
Detection
of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with
Chronic Fatigue Syndrome. Vincent C. Lombardi,
Francis W. Ruscetti, Jaydip Das Gupta,Max A. Pfost, Kathryn S.
Hagen, Daniel L. Peterson, Sandra K. Ruscetti, Rachel K. Bagni,
Cari Petrow-Sadowski, Bert Gold, Michael Dean, Robert H.
Silverman, Judy A. Mikovits (Abstract) "Cell
culture experiments revealed that patient-derived XMRV is
infectious and that both cell associated and cell-free
transmission of the virus are possible. Secondary viral infections
were established in uninfected primary lymphocytes and indicator
cell lines following exposure to activated PBMCs, B cells, T
cells, or plasma derived from CFS patients. These findings raise
the possibility that XMRV may be a contributing factor in the
pathogenesis of CFS."
Supporting
Online Material
Full article reprint (8 October 2009) Science [DOI:
10.1126/science.1179052]
2007
Chronic
Fatigue Syndrome: Inflammation, Immune Function, and
Neuroendocrine Interactions.
Nancy G. Klimas, MD, Anne
O'Brien Koneru, MSN
"The preponderance of available research confirms that immune
dysregulation is a primary characteristic of CFS. New research has
further elucidated our understanding of the genomics of the
illness and the role of viral infection and reactivation in the
pathogenesis. Advances in the field should result in targeted
therapies to impact immune function, HPA axis regulation, and
persistent viral reactivation in CFS patients. Future research
investigating these important areas may lead to promising new
discoveries and options for treating CFS."
Immunoassay
with cytomegalovirus early antigens from gene products p52 and CM2
(UL44 and UL57) detect active infection in patients with chronic
fatigue syndrome. Beqaj
SH, Lerner AM, Fitzgerald JT. "Immunoassays that use
Early Antigen recombinant HCMV CM2 and p52 are five time more
sensitive than HCMV ELISA assay using viral lysate and are
specific in the detection and differentiation of active HCMV
infection in a subset of CFS patients."
Chronic
fatigue syndrome is associated with chronic enterovirus infection
of the stomach.
John K S Chia, Andrew Y Chia; J Clin Pathol 2007
"A total of 135/165 (82%) biopsy specimens stained positive for
VP1 [an enteroviral protein] within parietal cells.... Taken
together, the findings of enteroviral protein, RNA and the growth
of non-cytopathic viruses in the stomach tissue of CFS patients,
years after initial infection, suggest a strong association
between enteroviral persistence/infection and CFS. [Note]:
Enteroviruses cause acute respiratory and gastrointestinal
infection, with well-documented tropism for the central nervous
system, heart and muscles."
2006
Use
of valganciclovir in patients with elevated antibody titers
against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV)
who were experiencing central nervous system dysfunction including
long-standing fatigue.
Kogelnik AM, Loomis K, Hoegh-Petersen M, Rosso F, Hischier C,
Montoya JG. "Nine out of 12 (75%) patients experienced
near resolution of their symptoms, allowing them all to return to
the workforce or full time activities."
A
first study of cytokine genomic polymorphisms in CFS: Positive
association of TNF-857 and IFNgamma 874 rare alleles.
(Abstract)
N. Carlo-Stella [1], C. Badulli [2], A. De Silvestri [2], L.
Bazzichi [3], M. Martinetti [2], L. Lorusso [4], S. Bombardieri
[3], L.Salvaneschi [2], M. Cuccia [1] Affiliations: [1] University
of Pavia, [2] San Matteo Polyclinic Hospital, Pavia; [3] S. Chiara
Hospital, Pisa; [4] M. Mellini Hospital, Chiari, (BS), Italy.
"We hypothesize that CFS patients can have a genetic
predisposition to an immunomodulatory response of an inflammatory
nature probably secondary to one or more environmental insults of
unknown nature."
2005
The
role of enterovirus in chronic fatigue syndrome.
Journal: J of Clinical Pathology 2005;58:1126-1132, Author:
J K S Chia (Summary) "This review summarises the available
experimental and clinical evidence that supports the role of
enterovirus in chronic fatigue syndrome."
Chronic
fatigue syndrome is associated with diminished intracellular
perforin. Maher KJ, Klimas NG, Fletcher MA. Department
of Medicine, University of Miami Miller School of Medicine, Miami,
FL 33176, USA. "A significant reduction in the NK cell
associated perforin levels in samples from CFS patients, compared
to healthy controls, was observed. There was also an indication of
a reduced perforin level within the cytotoxic T cells of CFS
subjects, providing the first evidence, to our knowledge, to
suggest a T cell associated cytotoxic deficit in CFS. Because
perforin is important in immune surveillance and homeostasis of
the immune system, its deficiency may prove to be an important
factor in the pathogenesis of CFS and its analysis may prove
useful as a biomarker in the study of CFS."
(Abstract
only)
Cytokine
production and modulation: Comparison of patients with chronic
fatigue syndrome and normal controls. (Abstract) Akemi
Tomoda, Takako Joudoi, El-Mezayen Rabab, Tomoaki Matsumoto, T.H.
Park and Teruhisa Miike Department of Child Development, School of
Medicine, Kumamoto University, Kumamoto, Japan "CFS
patients showed significantly lower mRNA levels and transforming
growth factor-beta1 (TGF-β1) production. Cytokine dysregulation
affects CFS pathogenesis. TGF-β1 may aid treatment because it
affects CFS inflammatory characteristics."
Chronic
Fatigue Syndrome: Exercise Performance Related to Immune
Dysfunction (Abstract & Intro)
Jo Nijs; Mira Meeus; Neil R. Mcgregor; Romain Meeusen; Guy De
Schutter; Elke Van Hoof; Kenny De Meirleir "To date, the
exact cause of abnormal exercise response in chronic fatigue
syndrome (CFS) remains to be revealed, but evidence addressing
intracellular immune deregulation in CFS is growing."
"It is hypothesized that in CFS patients, 1) both PRK activation
and consequent elevated NO levels predict poor exercise
performance during a graded exercise cycle test, and 2)
deregulation of the 2-5A synthetase/RNase L pathway is associated
with poor exercise performance during a graded exercise cycle
test."
2',5'-Oligoadenylate
size is critical to protect RNase L against proteolytic cleavage
in chronic fatigue syndrome. (Abstract)
Fremont M, El Bakkouri K, Vaeyens F, Herst CV, De Meirleir K,
Englebienne P. RED Laboratories, Pontbeek 61, B-1731 Zellik,
Belgium. "The presence of the truncated 37-kDa RNase L in
PBMC extracts is therefore likely to result, not only from the
abnormal activation of inflammatory proteases, but also from a
dysregulation in 2-5A synthetase induction or activation towards
the preferential production of 2-5A dimers."
2004
Increased
neutrophil apoptosis in chronic fatigue syndrome.
Kennedy G, Spence VA, Underwood C and Belch JJF. Institution:
Vascular Diseases Research Unit, The Institute of Cardiovascular
Research, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.
"We have shown that patients with CFS also have increased
neutrophil apoptosis and higher levels of TGF-b1. We suggest that
increased neutrophil apoptosis and inhibition of transmigration of
neutrophils by higher TGF-b1 levels may be indicative of a
persistent viral infection or a toxic state giving rise to many of
the symptoms which characterize CFS. It might also be that
increased apoptosis merely reflects a quicker turnover of
neutrophils in this condition, but either way the data presented
here provides convincing evidence that many patients with CFS have
an underlying detectable abnormality."
(Abstract
only)
Clinical
and biochemical characteristics differentiating chronic fatigue
syndrome from major depression and healthy control populations:
relation to dysfunction and RNase L pathway. Suhadolnik,
RJ., Peterson, DL., Reichenbach, NL., Roen, G., Metzger, M.,
McCahan, J., O'Brien, K., Welsch, S., Gabriel, J., Gaughan, JP and
McGregor, NR. "The correlation between abnormalities in
the RNase L pathway and impaired NK cell function (r=.21, p<.006)
suggests that both may be part of the same underlying disease
mechanism, at least in this homogeneous population of very
disabled CFS patients. The results of the present study
support the cytokine/immune activation model in this
well-characterized CFS patient group."
High
levels of type 2 cytokine-producing cells in chronic fatigue
syndrome. (Abstract) Skowera A, Cleare A, Blair D,
Bevis L, Wessely SC, Peakman M. Department of Immunology, Guy's,
King's & St Thomas's School of Medicine, King's College London,
London, UK. "Concluding, we show evidence for an effector
memory cell bias towards type 2 responsiveness in patients with
CFS, as well as ongoing type 0 immune activation in unstimulated
cultures of peripheral blood cells."
2003
RNase
L in Health and Disease -- What Did We Learn Recently?
Author: Patrick Englebienne, Affiliation: Patrick
Englebienne is affiliated with the Department of
Nuclear Medicine, Free University of Brussels, Brugmann University
Hospital, Place van Gehuchten 4, B-1O20 Brussels, Belgium, and RED
Laboratories N. V., Pontbeek 61, B-1731 Zellik, Belgium
"A deregulation in this pathway has been documented in immune
cells of chronic fatigue syndrome patients which involves the
presence of a catalytically active truncated RNase L. This protein
escapes the normal regulation which implies the development of a
cascade of unwanted cellular events. The present article reviews
our current understanding of this deregulation, enlightens its
relevance in the pathological process and proposes new targets for
therapeutic development."
Enterovirus
related metabolic myopathy: a postviral fatigue syndrome.
R J M Lane, B A Soteriou, H Zhang, L C Archard "There
is an association between abnormal lactate response to exercise,
reflecting impaired muscle energy metabolism, and the presence of
enterovirus sequences in muscle in a proportion of CFS patients."
Deregulation
of the 2.5A synthetase RNase L antiviral pathway by Mycoplasma spp.
in subsets of Chronic Fatigue Syndrome. Jo Nijs1,
MSc; Kenny De Meirleir1,2, MD, PhD; Danny Coomans3, PhD; Pascale
De Becker1, PhD; Garth L. Nicolson4, PhD1. Department of Human
Physiology – Faculty of Physical Education and Physiotherapy –
Vrije Universiteit Brussel (V.U.B.), Belgium2. Chronic Fatigue
Clinic – Vrije Universiteit Brussel (V.U.B.)3. School of
Mathematical and Physical Sciences-James Cook University,
Australia4. Institute for Molecular Medicine, Huntington Beach,
California, USA "The present study provides new insight
into the complex nature of CFS. These data clearly suggest a
co-morbid pathobiological pathway between Mycoplasma spp. and a
deregulation of the 2,5A synthetase RNase L antiviral pathway in
subsets of CFS. Patients fulfilling the 1994 CDC case definition
for CFS that present with a Mycoplasma infection are more likely
to show a deregulated RNase L antiviral pathway compared to
non-infected patients."
RNase
L Levels in Peripheral Blood Mononuclear Cells:
37-Kilodalton/83-Kilodalton Isoform Ratio Is a Potential Test for
Chronic Fatigue Syndrome. Kiet Phong Tiev,1*
Edith Demettre,2 Philippe Ercolano,1 Lionel Bastide,2 Bernard
Lebleu,2 and Jean Cabane1 Service de Me´decine Interne, Hoˆpital
Saint Antoine, 75571 Paris Cedex 12,1 and UMR 5124 CNRS,
Universite´ Montpellier 2, 34293 Montpellier Cedex 5,2 France
"...our findings provide additional arguments to support the
hypothesis that increased proteolytic activity leads to the
accumulation of a 37-kDa binding polypeptide in PBMC extracts from
CFS patients and could be considered as a potential diagnostic
marker."
2001
Prevalence
in the Cerebrospinal Fluid of the Following Infectious Agents in a
Cohort of 12 CFS Subjects: Human Herpes Virus-6 and 8; Chlamydia
Species; Mycoplasma Species; EBV; CMV; and Coxsackievirus
(Abstract) Susan Levine, MD; affiliated with the New
Jersey Chronic Fatigue Syndrome Association. "...we
sought to determine the prevalence of HHV-6, HHV-8, Epstein-Barr
Virus (EBV), cytomegalovirus (CMV), Mycoplasma species, Chlamydia
species, and Coxsackie virus in the spinal fluid of a group of 12
patients with CFS. Although we intended to search mainly for
evidence of actively replicating HHV-6, a virus that has been
associated by several researchers with this disorder, we found
evidence of HHV-8, Chlamydia species, CMV and Coxsackie virus in
6/12 samples."
Cytokines
and chronic fatigue syndrome. (Abstract) Patarca
R. Department of Medicine, University of Miami School of
Medicine, Florida 33101, USA. "Chronic fatigue syndrome (CFS)
patients show evidence of immune activation, as demonstrated by
increased numbers of activated T lymphocytes, including cytotoxic
T cells, as well as elevated levels of circulating cytokines.
Nevertheless, immune cell function of CFS patients is poor, with
low natural killer cell cytotoxicity (NKCC), poor lymphocyte
response to mitogens in culture, and frequent immunoglobulin
deficiencies, most often IgG1 and IgG3. Immune dysfunction in CFS,
with predominance of so-called T-helper type 2 and proinflammatory
cytokines, can be episodic and associated with either cause or
effect of the physiological and psychological function derangement
and/or activation of latent viruses or other pathogens."
Immunotherapy
of chronic fatigue syndrome: therapeutic interventions aimed at
modulating the Th1/Th2 cytokine expression balance.
Patarca-Monero, R, Klimas, NG and Fletcher, MA. "Based on
the postulates of viral and autoimmune aetiologies of CFS, several
interventions have been designed and tested by different research
groups around the world, including the United States, Sweden,
United Kingdom, Italy, and Japan. This review addresses those
interventions aimed at altering the balance of certain cytokines,
the mediators of immune responses."
Characterization
of a 2',5'-oligoadenylate (2-5A)-dependent 37-kDa RNase L: azido
photoaffinity labeling and 2-5A-dependent activation. (Abstract)
Shetzline SE, Suhadolnik RJ. Department of Biochemistry and the
Fels Institute for Cancer Research and Molecular Biology, Temple
University School of Medicine, Philadelphia, Pennsylvania 19140,
USA. "Upregulation of key components of the
2',5'-oligoadenylate (2-5A) synthetase/RNase L pathway has been
identified in extracts of peripheral blood mononuclear cells from
individuals with chronic fatigue [corrected] syndrome, including
the presence of a low molecular weight form of RNase L."
2000
A
37 kDa 2-5A binding protein as a potential biochemical marker for
chronic fatigue syndrome. (Abstract) De Meirleir
K, Bisbal C, Campine I, De Becker P, Salehzada T, Demettre E,
Lebleu B. Department of Human Physiology and Medicine, Vrije
Universiteit Brussels, Belgium. "The presence of a 37 kDa
2-5A binding protein in extracts of peripheral blood mononuclear
cells may distinguish patients with chronic fatigue syndrome from
healthy subjects and those suffering from other diseases."
Review:
Immunology of Chronic Fatigue Syndrome. Roberto Patarca,
Timothy Mark, Mary Ann Fletcher and Nancy KlimasE. M. Papper
Laboratory of Clinical ImmunologyDepartment of Medicine
(R-42)University of Miami School of Medicine. "A review
of the literature on the immunology of CFS reveals that people who
have Chronic Fatigue Syndrome (CFS) have two basic problems with
immune function that have been documented by most research groups:
[1] immune activation, as demonstrated by elevation of activated T
lymphocytes, including cytotoxic T cells, as well as elevations of
circulating cytokines; and [2] poor cellular function, with low
natural killer cell cytotoxicity (NKCC), poor lymphocyte response
to mitogens in culture, and frequent immunoglobulin deficiencies,
most often IgG1 and IgG3."
1999
Interferon-induced
proteins are elevated in blood samples of patients with chemically
or virally induced chronic fatigue syndrome. (Abstract)
Vojdani A, Lapp CW. Immunosciences Laboratory Inc., Beverly Hills,
California, USA. "We conclude that 2-5A and PKR are not
only biomarkers for viral induction of CFS, but biomarkers to
other stressors that include MTBE and Benzene."
Comparative
Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of
Patients with Chronic Fatigue Syndrome (Abstract)
Contributors: MaryAnn Fletcher PhD, Department of Medicine,
University of Miami, Miami, FL, 33101, Kevin Maher, Department of
Medicine, University of Miami, Roberto Patarca-Montero MD,PhD,
Miami Beach, FL, 33160, Nancy Klimas MD, VA Medical Center, Miami,
FL, 33125. "CFS has been proposed to be a disease of
autoimmune etiology and in this respect it is interesting to note
that decreased proportions of CD45RA+ T (''naive'') cells are also
seen in the peripheral blood of patients with autoimmune
diseases."
1997
Enterovirus
infections in new disguise. (Abstract.
Article in Swedish) Fohlman J, Friman G, Tuvemo T.
Infektionskliniken, Akademiska sjukhuset, Uppsala. "Persistent
enteroviral infection or recurrent infections and/or
virus-stimulated autoimmunity might contribute to the development
of diseases with hitherto unexplained pathogenesis, such as post
polio syndrome, dilated cardiomyopathy, juvenile (type 1) diabetes
and possibly some cases of chronic fatigue syndrome."
Biochemical
evidence for a novel low molecular weight 2-5A-dependent RNase L
in chronic fatigue syndrome. (Abstract) Suhadolnik RJ,
Peterson DL, O'Brien K, Cheney PR, Herst CV, Reichenbach NL, Kon
N, Horvath SE, Iacono KT, Adelson ME, De Meirleir K, De Becker P,
Charubala R, Pfleiderer W. Department of Biochemistry, Temple
University School of Medicine, Philadelphia, PA, USA. "Evidence
is provided indicating that the RNase L enzyme dysfunction in CFS
is more complex than previously reported."
1994
Dysregulated
expression of tumor necrosis factor in chronic fatigue syndrome:
interrelations with cellular sources and patterns of soluble
immune mediator expression. (Abstract) Patarca R,
Klimas NG, Lugtendorf S, Antoni M, Fletcher MA. E. M. Papper
Laboratory of Clinical Immunology, University of Miami School of
Medicine, Florida. "These findings point to polycellular
activation and may be relevant to the etiology and nosology of CFS."
1990
Myalgic
encephalomyelitis--a persistent enteroviral infection?
(Abstract) Dowsett EG, Ramsay AM, McCartney RA, Bell EJ.
Basildon Hospital, Essex, UK. "This illness is
distinguished from a variety of other post-viral states by an
unique clinical and epidemiological pattern characteristic of
enteroviral infection. Prompt recognition and advice to avoid
over-exertion is mandatory. Routine diagnosis, specific therapy
and prevention, await further technical advances." |
