Immunoassay with cytomegalovirus early antigens from gene products p52 and CM<sub>2</sub>(UL44 and UL57) detects active infection in patients with chronic fatigue syndrome

Beqaj, Safedin; Lerner, A. Martin; Fitzgerald, James T.

doi:10.1136/jcp.2007.050633

Cited by 30 publications

(21 citation statements)

References 25 publications

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“…Assays of blood in some patients indicate altered T helper (Th)1 and Th2 cytokine profiles, natural killer cell function and activation of the 2-5A synthetase/ RNase L antiviral pathway. [1][2][3] Infection has been reported with a wide range of viruses and bacteria, 4 including Epstein-Barr virus, [5][6][7][8] human herpes viruses 6 and 7, [9][10][11] enteroviruses, 7,12 cytomegalovirus 13,14 and lentiviruses, 15 as well as chlamydia, 7 mycoplasma 16 and borrelia species. 17 An association of ME/CFS with central nervous system (CNS) dysfunction is supported by imaging studies documenting cerebral hypoperfusion and increased white matter T2 signal consistent with chronic inflammation 18 in addition to regional differences in gray 19 and/ or white matter.…”

Section: Introductionmentioning

confidence: 99%

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

et al. 2015

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Myalgic encephalomyelitis/chronic fatigue syndrome is an unexplained debilitating disorder that is frequently associated with cognitive and motor dysfunction. We analyzed cerebrospinal fluid from 32 cases, 40 subjects with multiple sclerosis and 19 normal subjects frequency-matched for age and sex using a 51-plex cytokine assay. Group-specific differences were found for the majority of analytes with an increase in cases of CCL11 (eotaxin), a chemokine involved in eosinophil recruitment. Network analysis revealed an inverse relationship between interleukin 1 receptor antagonist and colony-stimulating factor 1, colony-stimulating factor 2 and interleukin 17F, without effects on interleukin 1α or interleukin 1β, suggesting a disturbance in interleukin 1 signaling. Our results indicate a markedly disturbed immune signature in the cerebrospinal fluid of cases that is consistent with immune activation in the central nervous system, and a shift toward an allergic or T helper type-2 pattern associated with autoimmunity.

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Section: Introductionmentioning

confidence: 99%

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

et al. 2015

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“…The wells were washed three times in washing buffer and bound HRP label was detected with 3,3′ 5.5 tetramethyl benzidine as substrate for 30 minutes in the dark, after which the color reaction was stopped by the addition of stop solution as recommended by the manufacturer's manual. The absorbance was measured at 450/650 nm using Biotech reader (Biotech Clinical Laboratories, Inc., Farmington MI, USA) [18]. A value of <18 is considered negative.…”

Section: Methodsmentioning

confidence: 99%

“…We earlier reported elevated HCMV IgM serum antibody titers to early proteins p52 (UL44) and CM2 (UL 44 – UL 57) in 61 CMV subset CFS patients. These early CMV encoded elevated serum antibody titers were not present in a comparison group of normal patients [18]. We also discovered elevated serum antibody titers to EBV EA(D) in 86 of the 106 (81%) CFS patients with group A CFS [2].…”

Section: Introductionmentioning

confidence: 99%

Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset

et al. 2012

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BackgroundA defined diagnostic panel differentiated patients who had been diagnosed with chronic fatigue syndrome (CFS), based upon Fukuda/Carruthers criteria. This diagnostic panel identified an Epstein-Barr virus (EBV) subset of patients (6), excluding for the first time other similar “clinical” conditions such as cytomegalovirus (CMV), human herpesvirus 6 (HHV6), babesiosis, ehrlichiosis, borreliosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and adult rheumatic fever, which may be mistakenly called CFS. CFS patients were treated with valacyclovir (14.3 mg/kg q6h) for ≥12 months. Each patient improved, based upon the Functional Activity Appraisal: Energy Index Score Healthcare Worker Assessment (EIPS), which is a validated (FSS-9), item scale with high degree of internal consistency measured by Cronbach's alpha.MethodsAntibody to EBV viral capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and neutralizing antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase were assayed serially approximately every three months for 13–16 months from sera obtained from patients with CFS (6) and from sera obtained from twenty patients who had no history of CFS.ResultsAntibodies to EBV EA(D) and neutralizing antibodies against the encoded-proteins EBV DNA polymerase and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) were present in the EBV subset CFS patients. Of the sera samples obtained from patients with CFS 93.9% were positive for EA(D), while 31.6% of the control patients were positive for EBV EA(D). Serum samples were positive for neutralizing antibodies against the EBV-encoded dUTPase (23/52; 44.2%) and DNA polymerase (41/52; 78.8%) in EBV subset CFS patients, but negative in sera of controls.ConclusionsThere is prolonged elevated antibody level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset of CFS patients, suggesting that this antibody panel could be used to identify these patients, if these preliminary findings are corroborated by studies with a larger number of EBV subset CFS patients.

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“…CFS patients are also often found to be infected with B. burgdorferi [204], C. pneumoniae [197,201,205], cytomegalovirus [206], B19 parvovirus [207] and HHV-6 [197,201,208]. However, not all studies on infections in CFS patients have been accurate.…”

Section: Chronic Fatigue Syndrome (Cfs)mentioning

confidence: 99%

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

Nicolson

Settineri

Ellithorpe³

2014

FFHD

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Background: Many chronic diseases and illnesses are associated with one or more chronic infections, dysfunction of mitochondria and reduced production of ATP. This results in fatigue and other symptoms that occur in most if not all chronic conditions and diseases.Methods: This is a review of the published literature on chronic infections in neurodegenerative diseases and fatiguing illnesses that are also typified by mitochondrial dysfunction. This contribution also reviews the use of natural supplements to enhance mitochondrial function and reduce the effects of chronic infections to improve overall function in various chronic illnesses.Results: Mitochondrial function can be enhanced by the use of various natural supplements, notably Lipid Replacement Therapy (LRT) using glyerolphospholipids and other mitochondrial supplements. In various chronic illnesses that are characterized by the presence of chronic infections, such as intracellular bacteria (Mycoplasma, Borrelia, Chlamydia and other infections) and viruses, LRT has proven useful in multiple clinical trials. For example, in clinical studies on chronic fatigue syndrome, fibromyalgia syndrome and other chronic fatiguing illnesses where a large majority of patients have chronic infections, LRT significantly reduced fatigue by 35-43% in different clinical trials and increased mitochondrial function. In clinical trials on patients with multiple intracellular bacterial infections and intractable fatigue LRT plus other mitochondrial supplements significantly decreased fatigue and improved mood and cognition.Conclusions: LRT formulations designed to improve mitochondrial function appear to be useful as non-toxic dietary supplements for reducing fatigue and restoring mitochondrial and other cellular membrane functions in patients with chronic illnesses and multiple chronic infections. BackgroundPatients with chronic neurodegenerative, neurobehavioral and fatiguing illnesses commonly test positive for systemic and central nervous system (CNS) bacterial and viral infections [1][2][3]. In addition, other chronic illnesses where neurological manifestations are routinely found, such as autoimmune diseases and other chronic illnesses and disorders, also show evidence of systemic bacterial and viral infections that could be important in disease inception, progression and/or enhancing the types and severities of signs and symptoms [2,3].Evidence of bacterial infections, such as Mycoplasma species, Chlamydia pneumoniae, Borrelia burgdorferi, among others, and viruses, such as human herpesvirus (HHV), cytomegalovirus (CMV), human herpes viruses (HHV) and other viral infections, have revealed high rates of infection in the illnesses listed above that were not found in control populations [1][2][3]. Although the specific roles of chronic infections in various diseases and their pathogeneses have not been carefully determined, the data suggest that chronic bacterial and/or viral infections are common features of essentially all progressive chronic diseases [1][2][3].An...

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Immunoassay with cytomegalovirus early antigens from gene products p52 and CM₂(UL44 and UL57) detects active infection in patients with chronic fatigue syndrome

Abstract: Immunoassays that use early antigen recombinant HCMV CM(2) and p52 are five times 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 patients with CFS.

Cited by 30 publications

References 25 publications

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

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Immunoassay with cytomegalovirus early antigens from gene products p52 and CM2(UL44 and UL57) detects active infection in patients with chronic fatigue syndrome

Abstract: Immunoassays that use early antigen recombinant HCMV CM(2) and p52 are five times 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 patients with CFS.

Cited by 30 publications

References 25 publications

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome

Antibody to Epstein-Barr Virus Deoxyuridine Triphosphate Nucleotidohydrolase and Deoxyribonucleotide Polymerase in a Chronic Fatigue Syndrome Subset

Neurodegenerative and Fatiguing Illnesses, Infections and Mitochondrial Dysfunction: Use of Natural Supplements to Improve Mitochondrial Function.

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Product

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Immunoassay with cytomegalovirus early antigens from gene products p52 and CM₂(UL44 and UL57) detects active infection in patients with chronic fatigue syndrome