List of all Abnormal Findings

Research Findings

All findings summarized (and continuously updated).

  • General
  • An estimated 17 million people worldwide have CFIDS.
  • 60-80% of CFIDS presents with acute onset of illness (post-viral)
  • post-exertional malaise
  • A low oxygen extraction and a high ΔQ’/ΔV’O2 were consistent with a metabolic cause for exercise intolerance in 70% of CFS patients. source
  • fatigue that lasts for longer than 6 months, that doesn’t go away with sleep/rest
  • cognitive impairment (memory/concentration, ‘brainfog’)
    (objective impairment in attention and memory but with good mobilization of effort and without exaggerated suggestibility)
  • high incidence of allergies
  • low placebo effect
  • severity of the condition shows through SF12 for both physical health and mental health.
  • CFIDS patients have a higher incidence of cancer
  • Skeletal muscle and cardiac bioenergetic abnormalities
  • 738 unique proteins in spinal fluid
  • contrary to what is often assumed, placebo response in CFIDS is low. source
  • difference between early stages (<3 years ill) and long-term (>3 years) source
  • Metabolism/Energy
  • Patients with CFS showed abnormalities in 20 metabolic pathways (despite different triggering events for their illness). 9 of those were for both male and female, 11 showed gender differences. source
  • 80% of 612 metabolic pathways are decreased source
  • Sphingolipids and Glycosphingolipids decreased source
  • Phospholipids decreased. source
  • phospholipid, PC (containing the essential omega 3 fatty acid docosahexaenoic acid (DHA, C22:6),  and oleic acid (C18:1) )  increased. This pattern is opposite to that seen in response to acute infection and the CDR  and metabolic syndrome. source
  • Purines decreased. Plasma uric acid was decreased in males. Plasma adenosine was decreased in females. source
  • Aromatic Amino Acid Metabolites from microbiome decreased. Plasma 4-hydroxyphenyllactic acid decreased in males. Plasma phenyllactic acid decreased in females. source
  • Plasma lathosterol was decreased in both males and females  source
  • Total plasma cholesterol, desmosterol, cortisol, and aldosterone were normal in both males and females  source
  • Flavin Adenine Dinucleotide decreased. source
  • Cholesterol and bile acid synthesis through the lathosterol pathway decreased. source
  • Plasma chenodeoxycholic acid decreased in females  source
  • Pyrroline-5-Carboxylate and Arginine Were Increased. source
  • Branch Chain Amino Acid Metabolic Intermediates Were Decreased. 2-Hydoxyisocaproic acid decreased.
  • Hydroxyproline was increased in females source
  • lower levels of L-glutathione and increased oxidative stress (vicious cycle, source)
  • elevated 8-OH-deoxy guanosine (marker for total oxidative stress source)
  • unvaforable lipid profile, signs of oxidative stress induced damage to lipids and proteins source
  • mitochondrial dysfunction / abnormal mitochondrial degeneration (neutrofils). degree of dysfunction correlated with severity of illness.
  • high concentration of H2S in urine (H2S normally present in body in low dosage, but high dose is very toxic)
  • over 40% of CFIDS patients have coenzyme Q10 deficiency.
  • Mild to severe atrophy of type II fibres with a mild to moderate excess of lipid. Branching and fusion of mitochondrial cristae. Mitochondrial degeneration with swelling, vacuolation, myelin figures and secondary lysosomes. (50 patients, controls showed no abnormalities) source
  • increased COX-2 production (Maes – source? mentioned in source)
  • Readily switch to Anaerobic metabolism in stead of aerobic (Sarah Myhill link source?)
  • Deficiency of CoQ10 has been found in some CFS patients . CoQ10 is a mitochondrial nutrient, which acts as an essential cofactor for the production of ATP and displays significant antioxidant activities and anti-inflammatory effects. Maes – source? mentioned in source
  • Decreased levels of CoQ10 and ATP , increased levels of lipid perocidation (indicating oxidative stress induced damage). source
  • lower urinary cortisol to creatinine ratio source
  • higher plasma norepinephrine level , and serum C-reactive protein concentration source
  • Schisandra chinensis polysaccharide improved metabolites in rats. The TCA cycle metabolic pathways and the alanine, aspartate and glutamate metabolism were identified as significant metabolic pathways involved with SCP. The therapeutic mechanism of SCP against CFS was partially due to the restoration of these disturbed pathways. (link to poly)
  • Muscle/Endurance/Stamina/ Cardio
  • In the basal state, CFS cultures showed increased myogenin expression but decreased IL6 secretion during differentiation compared with control cultures source
  • 16hr EPS no increase in both AMPK phosphorylation and glucose uptake (controls: significant increase) – exercise-related defect source
  • IL6 secretion in response to EPS was significantly reduced in CFS source
  • Maximal cardiopulmonary exercise test. Lousy 24h/48h recovery rates in CFS (patients 0%/4% vs 85%/100% controls) source
  • post-exertional malaise is composed of two empirically different experiences, one for generalized fatigue and one for muscle-specific fatigue. source
  • LVEF end-diastolic diameter  as well as body surface area corrected LV end-diastolic volume, stroke volume , and mass were significantly lower in patients. source
  • Wall motion abnormalities were observed in 4 patients and contrast enhancement (fibrosis) in 5 (12 patients total were tested) source
  • Immune system
  • serum BAFF levels increased – chronically activated B-lymphocyte system? source
  • There were no significant differences in baseline serum BAFF levels between patients with mild, moderate, or severe ME/CFS. source
  • No difference in APRIL serum levels between ME/CFS and controls. source
  • presence of auto-antibodies
  • more or less normal B-cell compartment, a biased NK-cell phenotype and a poorly responsive T-cell compartment (reason for  intercurrent viral infections?) source
  • reduced T cell response to mitogens and certain antigens
  • increased HLA-DR activation markers
  • decrease in antibody dependent cell mediated cytotoxicity
  • mast cell activation
  • decreased NK function
  • protein kinase genes in isolated NK cells: 37 genes were significantly upregulated and 55 genes were significantly downregulated source
  • NK cell cytotoxic activity significantly lower (due to decreased functional capacity) source
  • significant reduction in the NK cell associated perforin levels source
  • reduced perforin level within the cytotoxic T cells – T cell associated cytotoxic deficit source
  • skewed NK cell population with high CD69 and low CD25 expression source
  • NKp46 elevated source
  • altered essential fatty acid (EFA) status
  • the system is biased towards a T-helper (Th) 2 type immunity-oriented pattern
  • weakened Th1 and Th17 immune response (as well as Th2), consistent with viral trigger
  • consistent and significantly attenuated patterns of Th1 and Th17 immune responses , well-established Th2 inflammatory millieu source need to add broderick et al source
  • increased markers of peripheral inflammation
  • increased CRP
  • increased auto-antibodies
  • activation of immuno-inflammatory pathways, increased bacterial translocation, autoimmune responses to serotonin (5-HT). source
  • IgD, IgG, IgA, IgM unchanged source and source
  • Significant changes were observed in B-cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-α and IFN-γ source
  • Significantly reduced numbers of IFN-γ responses source
  • lack of EBNA-1-IgG.  source
  • elevated VCA-IgM was found more frequently in patients source
  • No difference in levels of VCA-IgG, CMV-specific IgM and levels of IgG . source
  • Tregs increased source
  • Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation source
  • greater numbers of naive B cells as a percentage of lymphocytes, greater numbers of naive B cells as a percentage of B cells, greater numbers of transitional B cells, reduced numbers of plasmablasts. Cause unclear, may suggest a subtle tendency to autoimmunity. source
  • Similar absolute numbers of T, B, NK. source and source
  • TGF-β – seems to be upregulated source
  • leptin increased source
  • increased resistin source
  • Cancer
  • Increased risk of Non Hodgkins Lymphoma (NLH, specifically types DLBCL and MZL) source
  • Increaased risk of kidney cancer source
  • Increased risk of pancreatic cancer source
  • Inverse association with breast cancer source
  • Inverse association with cancer of the oral cavity and pharynx. source
  • No association with brain tumor risk. source
  • Cytokines 
  • cytokine levels correlated to early/later stages (<3/>3 years sick)! source
  • high level of pro-inflammatory cytokines (influence NK, and HPA axis!) also known to cause extreme fatigue
  • lowered proinflammatory cytokines source
  • low level of anti-inflammatory cytokines source
  • CSF1 decreased  source
  • LTα increased
  • IL-1α increased source
  • IL-1RA increased source
  • IL1-β
  • IL-2 decreased (EBV) source
  • IL-4 increased source
  • IL-5 increased
  • IL-6 increased
  • IL-6 decreased  source
  • IL-6 secretion in response to EPS significantly reduced  source
  • IL-8 increased source
  • IL-8 decreased source
  • IL12p40 increased source
  • TNF-α increased source
  • TNF-α decreased (EBV) source
  • TNF-β decreased  source
  • IL-10 decreased source
  • IL-10 unchanged (EBV)source
  • IL-13 decreased
  • IL-13 increased (early stages) source
  • IL-15 decreased
  • IL-17A decreased  (later stages) source
  • IL-17A  increased (early stages) source
  • IP-10 decreased source
  • sFasL decreased source
  • TRAIL/ TNFSF10  increased source
  • MCP1 increased source
  • SCF / SF increased source
  • type 2 helper cell dominate cytokine profile source
  • Patients with serotonin( 5-HT ) autoimmune activity displayed higher TNFα, IL-1 and neopterin and increased IgA responses against LPS of commensal bacteria than those without 5-HT autoimmune activity. source
  • Lymphocytes (because some research contradicts eachother these are listed by cell type)
  • abnormal activity of T lymphocyte subsets
  • clonal populations of gd T-cells
  • PDGFBB decreased source
  • CD2+CD26+ elevated source (T cell/NK cell compartment activated_.
  • CD3+ decreased source
  • CD3+ (lymphocytes) unchanged source
  • CD4+/CD8+ ratio decreased source, no difference in cell death source
  • CD3/CD4 unbalanced ratio source
  • CD3+CD4+(lymphocytes)  unchanged source
  • CD3+CD8+ (lymphocytes) unchanged source
  • CD3-Cd56+ (NK) reduced source
  • no difference CD3-CD56+ (lymphocytes) source
  • triple producing CD4+ reduced source
  • double producing CD4+ reduced source
  • CD4+ decreased source
  • CD5 unchanged source increased source?
  • CD56+CD3- reduced source
  • CD7 unchanged source
  • CD8+ increased
  • triple producing CD8+ reduced source
  • double producing CD8+ reduced source
  • CD10 unchanged source
  • CD11b decreased expression
  • CD16 – (NK) similar absolute % source
  • CD16+CD56– – (NK) similar source
  • CD19 – (B) similar absolute % source
  • CD19+ unchanged source
  • CD19+IgD+CD38highCD10+CD5+ – similar source
  • CD19+CD27highCD38high – similar source
  • CD19+IgD+IgM+CD27+CD1c+ – similar source
  • CD19+ B cells are replaced with CD20 B cells which are immature and poorly functioning (Rituxan kills these cells), CD19 severely reduced (creates B cells), unchanged source
  • CD20+ increased (correlated auto-antibody production), CD20 immature – correlation with tumors
  • CD21 increased (retrovirus ligand)
  • CD25 decreased source CD 25 increased source , CD25 – (Treg) increased, (NK) significantly lower expression source
  • CD27 increased source , unchanged source , CD27+ – (B) no significant differences source
  • CD28+ increased subsets, unchanged source
  • CD3 – (NK) similar absolute % , (T) similar absolute % source
  • CD3-CD56+CD16+ (NK) similar absolute % source
  • CD3+ subset – slightly unbalanced source
  • CD3+CD56+ – significantly lower frequency source
  • CD3+CD4+ – (T) similar absolute % source
  • CD3+CD8+ – (T) similar absolute % source
  • CD38 increased source? , decreased source
  • CD40L decreased source
  • CD4 – minor difference (increased), (T) similar absolute %, ex vivo significantly lower proliferation response source
  • CD4+CD25++FOXP3+ – (Treg) – significantly higher source
  • CD4+CD25++FOXP3+CD127– – (Treg) significantly higher source
  • CD45 (T) similar absolute % source
  • CD45RA+CCR7+CD27+CD28+ (naive memory cells) – similar source
  • CD45RA–CCR7+CD27+CD28+ (central memory cell) – similar source
  • CD45RA–CCR7-CD27+CD28+ (transitional memory cell) – similar source
  • CD45RA–CCR7-CD27+CD28- (effector memory cell) – similar source
  • CD45RA-CCR7-CD27-CD28- ( terminally diff. memory cell) – similar, but lower frequency (?) source
  • CD5 – higher expression (marker for impaired T cell response) source
  • CD56 significantly reduced (kills off  bad things), reduced source , CD56 (NK) similar absolute % source
  • CD56highCD16–  – (NK)  similar source
  • CD56+CD16+ – (NK) similarsource
  • CD57 – significantly lower staining intensity (similar %) source
  • CD69 decreased (= T cell activation marker) source ,  CD69 (NK) – signigicantly higher expression source
  • CD8 – minor difference, significantly lower activation and frequency of effector memory cells subset source
  • CD95+ increased source reduced source
  • FOXP3 – (Treg) increased source
  • Ki67 – lower in CD4 cells, similar in CD8 cells source
  • PD-1 – exhaustion marker, differences with control source
  • XMRV (turned out to be contamination of murine something that was used.)
  • 68/101 CFIDS patients XMRV+ (67%) – WPI
  • 8/218 Healthy people XMRV+ (3,7%) – WPI
  • 11/11 CFIDS patients XMRV+ confirmed – Cleveland Clinic
  • 0/11 healthy people XMRV+ (env) 1/11 healthy people XMRV+ (gag) – confirmed – Cleveland Clinic
  • gag/env CFIDS strain >99% similar to XMRV+ prostate cancer
  • XMRV expression is stimulated by androgens(hormones), cortisol and inflammation.
  • in the animal world that Xenotropic, polytroips and SSFV MLVs cause neuroimmune disease and lead to tumors
  • extreme increase in Cytokine and Chemokine Production
  • EBV and (TNFa activates)NF-κB activation can markedly increase XMRV production. Another study found a positive correlation between NF-κB production and severity of illness.
  • Co-infections
  • HHV-6, HHV-7
  • Active HHV6 and dual HHV6 + HHV7  infections were detected in CFS patients , not controls (17 CFIDS, 12 fatigue, 20 healthy).
    HHV-7 reactivation was also significantly higher in  patients. HHV6 variant B was predominant in CFS patients (12/13).
    HHV6/7 reactivation possibly linked to significant decrease of CD3 and CD4 , decrease of CD4/CD8 ratio . Increase of CD95. source
  • HHV6 – no significant difference between patients and controls. Both CFS and controls positive for HHV7 (high loads).
    (48 patients, 35 controls). source
  • Patients with CFS often have active β herpesvirus infections, suggesting an underlying immune deficiency.
  • HTLV
  • HTLV-2 gag gene, not identified in blood. No marker for CFIDS (21 patients, 21 CDC employees, 42 healthy controls) source
  • EBV
  • Levels of EBV, HHV, CMV similar in patient and control (10 patients, 10 control) source
  • EBV – no significant difference between patients and controls  (48 patients, 35 controls) source
  • EBV has long been suspected of involvement in CFS onset, but EBV is not consistently detected in all patients source
  • EBV was found in 15-30% of all biopsies source
  • 30% of CFS patients shows abnormal EBV serology. source
  • EBV-specific memory B cells are low or absent in most CFS patients. source
  • CFS patients show diminished T-cell cytokine response to EBV.source
  • CFS patients show reduced EBV-specific multifunctional memory T cells. source
  • There is evidence of enhanced latent EBV replication in CFS patients. source
  • EBNA-1-IgG is reduced in a subset of patients but total IgG and B-cell subpopulations are not different in EBNA-1-IgG positive and -negative CFS patients. source
  • HPV-B19
  • HPV-B19 has been the most reported CFS-associated virus source. Although several studies have detected parvovirus B19 DNA in the GI tract of CFS patients, it is not consistently detected in all patients source. Another difficulty is associating the onset of CFS with the presence of antibodies to HPV-B19.
  • Significant difference for HPV-B19 between patients and controls, may be relevant for a subset of patients.  (48 patients, 35 controls) source
  • Gut
  • low levels of Bifidobacteria
  • significant alterations in gut microbiota source, source
  • higher levels of aerobic bacteria
  • small intestinal bacterial overgrowth (SIBO)
  • increased D-lactic acid bacteria (-> mitochondrial dysfunction, affects CNS) source
  • low levels of Escherichia coli
  • raised IgA and IgM to LPS of gram negative enterobacteria . Increased gut permeability. IgA correlated to severity of illness.
  • Candida albicans in the faecal microflora during the acute phase of illness
  • Overgrown pathogenic bacteria found in the oral cavity and GI tract produce the “toxic gas” hydrogen sulfide (H2S) when they come in contact with heavy metals (H2S normally found in body, but higher in CFS), high levels of H2S caused by an intestinal overgrowth of Gram positive D/L lactate-producing bacteria play a major role in CFS and lead to a series of reactions in your body that leave cells devoid of oxygen and energy. source , source Meirleir.
  • altered essential fatty acid (EFA) status source
  • Neurological / Brain / Spinal Cord
  • Chronic fatigue has 738 unique proteins. (Lyme has 692). These are complement cascade proteins (which helps clear infectious pathogens) indicating infection and immunesystem response. This article  also found complement system proteins in cerebrospinal fluid from CFS patients which differentiated CFS patients from healthy controls. sources : UMDNJ, PLOSONE, BMC
  • Orthostatic Intolerance
  • Orthostatic hyperventilation (physiological response to hypovolemia/distal blood pooling!) source
  • many symptoms of CFS can be reproduced by selectively adding neuromuscular strain during the examination source
  • disturbed (re)activity of the autonomic nervous system, altered sympathetic-neural and sympathetic adrenomedulla reactivity.  Lower baseline and attenuated responses of epinephrine. source
  • Exercise stress -> subtle catecholaminergice hyporeactivity. source
  • no difference with controls in response to insulin tolerance test source
  • Patterns of abnormal visual attention source
  • Increased sympathetic activity/ reduced heart rate variability (HRV) at night. source
  • Fractional anisotropy increased in right arcuate fasciculus and right inferior longitudinal fasciculus (may reflect degeneration of crossing fibers or strengthening of short-range fibers)  source
  • Bilateral white matter atrophy source
  • Cortical thickness increased in both right arcuate end points, the middle temporal gyri, and one right ILF end point, the occipital lobe source
  • Fibromyalgia
  • Fibromyalgia is an immunologic disorder. The cytokine (IFN-γ, IL-6, IL-8, IL-10, MIP-1β , MCP-1, and MIP1-α ) responses to mitogenic activators of PBMC isolated from patients with FM were significantly lower than those of healthy individuals, implying that cell-mediated immunity is impaired in FM patients. This research resulted in a diagnostic test for fibromyalgia. source
  • Test can differentiate fibromyalgia from osteoarthritis and rheumatoid arthritis. Unique  spectral patterns and biochemical differences. source
  • Expression levels of peroxisome proliferator-activated receptor gamma-coactivator 1-alpha and transcription factor A were significantly lower in FM patients, Mitochondrial DNA was lower as well. These were normal in CFS patients. Mitochondrial dysfunction-dependent events could be a biomarker of differentiation between CFS and FM. source
  • coQ10 helps with Fibromyalgia pain