Tag: 2018

Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation

Abstract:

BACKGROUND: A recent in vitro pilot investigation reported Rituximab significantly reduced natural killer (NK) cell cytotoxicity in healthy donors. Chronic fatigue syndrome/Myalgic encephalomyelitis (CFS/ME) is a debilitating disorder of unknown etiology. A consistent finding is a significant reduction in NK cell cytotoxicity. Rituximab has been reported having questionable potential therapeutic benefits for the treatment of CFS/ME, however, the potential effects of Rituximab on NK cell cytotoxicity in CFS/ME patients are yet to be determined.

METHODS: A total of eight CFS/ME patients (48.63 ± 15.69 years) and nine non-fatigued controls (NFC) (37.56 ± 11.06 years) were included using the Fukuda case definition. Apoptotic function, lytic proteins and degranulation markers were measured on isolated NK cells using flow cytometry following overnight incubation with Rituximab at 10 μg/ml and 100 μg/ml.

RESULTS: There was a significant reduction in NK cell lysis between CFS/ME patients and NFC following incubation with Rituximab at 100 μg/ml at 12.5:1 and 6.25:1 effecter-target (E:T) ratios (p < 0.05). However, there was no significant difference for NFC following incubation with Rituximab at 10 μg/ml and 100 μg/ml. There was no significant difference between CFS/ME patients and NFC for granzyme A and granzyme B prior to incubation with Rituximab and following overnight incubation with Rituximab at 10 μg/ml. There was a significant decrease in granzyme B in CFS/ME patients compared to NFC with 100 μg/ml of Rituximab prior to K562 cells stimulation (p < 0.05). There was a significant increase in CD107a (p < 0.05) and CD107b expression (p < 0.01) in NFC after stimulation with K562 cells prior to incubation with Rituximab. There was a significant increase in CD107b expression between CFS/ME patients and NFC prior to incubation with Rituximab and without stimulation of K562 cells (p < 0.01). Importantly, there was a significant increase in CD107b following overnight incubation with 100 μg/ml of Rituximab in NFC prior to K562 cells stimulation (p < 0.01).

CONCLUSION: This study reports significant decreases in NK cell lysis and a significant increase in NK cell degranulation following Rituximab incubation in vitro in CFS/ME patients, suggesting Rituximab may be toxic for NK cells. Caution should be observed in clinical trials until further investigations in a safe and controlled in vitro setting are completed.

Source: Eaton N, Cabanas H, Balinas C, Klein A, Staines D, Marshall-Gradisnik S. Rituximab impedes natural killer cell function in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients: A pilot in vitro investigation.BMC Pharmacol Toxicol. 2018 Mar 27;19(1):12. doi: 10.1186/s40360-018-0203-8.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870391/ (Full article)

Please Help David Tuller, Our Champion!

David Tuller’s fundraiser is now live! Tuller has been tireless in his battle against the GET/CBT ideological onslaught! He has much more work to do and he needs our support.

Tuller has been touring the globe, speaking about the harm the PACE trial has caused ME/CFS patients. Recently, he co-authored a critical paper, Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT, that was published in BMC Psychology.

Tuller has written more than seventy-five  posts on Vincent Racaniello’s Virology Blog, spanning seven years. His articles comprise a full history of how the PACE trial was used to mislead health care providers into thinking ME/CFS could be cured with “a walk and a talk.” Tuller has taken on some of the authors of the PACE study and, despite threats from them, has continued to challenge their findings.

Last year, Tuller successfully raised money through Crowdrise  in order to continue investigating and blogging about the PACE trial. The funds went to the School of Public Health at the University of California, Berkeley, which created a position for Tuller to continue his investigative work. Now, a year later, the funds have run out, and Tuller has to depend on the generosity of our community to continue his work.

Please donate HERE!

Drug hoped to treat CFS causes impaired immune function, Griffith study says

Reports that a drug used to treat autoimmune diseases and cancer could also treat Chronic Fatigue Syndrome (CFS) have been refuted by a new Griffith University study.

To be published in BMC Pharmacology and Toxicology, the study by Griffith’s National Centre for Neuroimmunology and Emerging Diseases(NCNED) concluded that the use of Rituximab in CFS patients could incur problems with their immune cells and is not beneficial as a potential treatment.

The Natural Killer (NK) cells have vital functions in fighting viruses, bacteria and tumours.

“We found that these functions were significantly impaired when exposed to Rituximab in CFS patients,” says Scientific Co-Director of NCNED, Professor Sonya Marshall-Gradisnik.

CFS – sometimes known as ME (myalgic encephalomyelitis) – is a complex illness characterised by impaired memory and concentration, metabolic, cardiac, gut and immune dysfunction and debilitating muscle pain and fatigue on exertion (also known as neuroimmune exhaustion).

It is estimated that the prevalence rate of CFS/ME worldwide is between 1 and 2 per cent.

Related to the ion channels

The Gold Coast NCNED team has discovered the illness is related to problems in the ion channels that allow calcium into the body’s cells. Calcium is required by almost every cell in the human body and is vital in helping the immune system destroy a virus or infection.

The team has proven that patients with CFS/ME have lower levels of calcium coming into their cells, that their cells store less calcium and that this is the basis of their illness.

Professor Don Staines, Clinical Co-Director of NCNED, says: “These results are important as NK cells are already known to have impaired function in CFS patients, suggesting certain doses of Rituximab may not be beneficial for the treatment of this condition.”

“Undertaking an initial study has enabled us to secure additional research funding from the national competitive grants process from the Mason Foundation where we can now undertake a larger study using this drug in vitro to validate our novel findings,” says Professor Staines.

First author for these world-first scientific findings was PhD student, Ms Natalie Eaton.  She will be presenting the study at an NCNED-sponsored conference later this year.  The focus of the conference will be promoting greater understanding of pathology and pharmacothereapeutics for CFS, through a Research, Innovation, Discovery, Learning and Education (RIDLE) model.

Source: Press Release: Griffith University, March 27, 2018.

Pediatric chronic fatigue syndrome: current perspectives

Abstract:

Pediatric chronic fatigue syndrome is an important illness as it is relatively common and also very disabling with a wide range of impacts on the child, the family, and health care systems. It is a complicated illness but the majority of children get better with specialist treatment. This literature review provides an update on the epidemiology of chronic fatigue syndrome/myalgic encephalomyelitis, including factors associated with it, and discusses the current evidence for treatment.

Source: Esther Crawley. Pediatric chronic fatigue syndrome: current perspectives. Dove Press. 29 March 2018 Volume 2018:9 Pages 27—33 https://www.dovepress.com/pediatric-chronic-fatigue-syndrome-current-perspectives-peer-reviewed-article-PHMT (You can download a PDF file of the full article.)

Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes

Abstract:

Background: Several studies have shown that patients with functional somatic syndromes (FSS) have, on average, deficient endogenous pain modulation (EPM), as well as elevated levels of negative affectivity (NA) and high comorbidity with depression and reduced resting heart rate variability (HRV) compared to healthy controls (HC). The goals of this study were (1) to replicate these findings and (2) to investigate the moderating role of NA, depression, and resting HRV in EPM efficiency within a patient group with fibromyalgia and/or chronic fatigue syndrome (CFS). Resting HRV was quantified as the root mean square of successive differences between inter-beat intervals (RMSSD) in rest, a vagally mediated time domain measure of HRV.

Methods: Seventy-eight patients with fibromyalgia and/or CFS and 33 HC completed a counter-irritation paradigm as a measure of EPM efficiency. Participants rated the painfulness of electrocutaneous stimuli (of individually calibrated intensity) on the ankle before (baseline phase), during (counter-irritation phase) and after (recovery phase) the application of a cold pain stimulus on the forearm. A larger reduction in pain in the counter-irritation phase compared to the baseline phase reflects a more efficient EPM.

Results: In contrast to our expectations, there was no difference between pain ratings in the baseline compared to counter-irritation phase for both patients and HC. Therefore, reliable conclusions on the moderating effect of NA, depression, and RMSSD could not be made. Surprisingly, patients reported more pain in the recovery compared to the counter-irritation and baseline phase, while HC did not. This latter effect was more pronounced in patients with comorbid depression, patients who rated the painfulness of the counter-irritation stimulus as high and patients who rated the painfulness of the electrocutaneous stimuli as low. We did not manage to successfully replicate the counter-irritation effect in HC or FSS patients. Therefore, no valid conclusions on the association between RMSSD, depression, NA and EPM efficiency can be drawn from this study. Possible reasons for the lack of the counter-irritation effect are discussed.

Source: Van Den Houte M, Van Oudenhove L, Van Diest I, Bogaerts K, Persoons P, De Bie J, Van den Bergh O. Negative Affectivity, Depression, and Resting Heart Rate Variability (HRV) as Possible Moderators of Endogenous Pain Modulation in Functional Somatic Syndromes. Front Psychol. 2018 Mar 6;9:275. doi: 10.3389/fpsyg.2018.00275. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845717/ (Full article)

Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia

Abstract:

OBJECTIVE: Chronic Fatigue Syndrome (CFS) is a disorder of unknown etiology associated with debilitating fatigue. One symptom commonly reported is disequilibrium. The goal of this study was to determine if CFS patients demonstrated verified balance deficits and if this was effected by comorbid fibromyalgia (FM).

METHODS: Twenty-seven patients with CFS (12 with comorbid FM) and 22 age and gender matched controls performed posturography.

RESULTS: Balance scores were significantly correlated with physical functional status in the CFS group (R2 = 0.43, P < 0.001), which was not found for mental functional status (R2 = 0.06, P > 0.5). CFS patients (regardless of FM) had significantly higher anxiety subscale of the vertigo symptom scale scores. CFS patients, regardless of FM status, demonstrated significantly lower overall composite balance scores (Controls – 78.8±1.5; CFS – 69.0±1.4, P < 0.005) even when controlling for anxiety and also had worse preference scores, indicating they relied on visual information preferentially even when visual information was incorrect. Interestingly, the CFS+FM group, not CFS only, demonstrated significantly worse vestibular scores (Controls – 70.2±2.4; CFS only – 67.9±3.8; CFS with FM – 55.4±4.6, P = 0.013).

INTERPRETATION: The major findings are that poor balance may be associated with poorer self-reported physical health. In addition, CFS patients seemed to rely preferentially on visual inputs, regardless of whether it was correct. The finding that vestibular function may be impaired in patients with CFS+FM but not in those with CFS alone suggests that the pathophysiology of CFS+FM may differ as has been suggested by some.

Source: Serrador JM, Quigley K, Zhao C, Findley T, Natelson BH. Balance deficits in Chronic Fatigue Syndrome with and without fibromyalgia. NeuroRehabilitation. 2018;42(2):235-246. doi: 10.3233/NRE-172245.

Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study

Abstract:

Purpose: One hallmark of chronic fatigue syndrome (ME/CFS) is task related worsening of fatigue. Global brain hypoperfusion, abnormal regional activation, and altered functional connectivity of brain areas associated with cognition and memory have been reported but remain controversial.

Methods: We enrolled 17 female participants fulfilling the CDC Criteria for ME/CFS and 16 matched healthy controls (HC). Using a 3T-Phillips Achieva MRI-scanner, pseudo-continuous arterial spin-labeling (pCASL), was used to study the dynamics of regional cerebral blood flow (rCBF) and their relationship to mental fatigue in ME/CFS patients and HC during a demanding cognitive task, i.e. modified Paced-Auditory-Serial-Addition-Testing (PASAT).

Results: ME/CFS subjects reported more fatigue than HC at baseline (p < .01). Global brain perfusion of ME/CFS and HC subjects was similar at rest. The PASAT resulted in significantly increased fatigue in ME/CFS participants and HC. Although not different between groups, overall CBF significantly increased over the first 3 min of the PASAT and then decreased thereafter. Regional CBF (rCBF) changes were significantly different between groups during the post-task recovery period. Whereas improvement of fatigue of ME/CFS subjects was associated with decreased rCBF in both superior temporal gyri (STG), precuneus, and fusiform gyrus, it was associated with increased rCBF in the same areas in HC.

Conclusions: Our results suggest that ME/CFS is associated with normal global CBF at rest and during a strenuous task (PASAT); however rCBF of several brain regions associated with memory, goal-oriented attention, and visual function was differentially associated with recovery from fatigue in ME/CFS patients and HC.

Source: Roland Staud, Jeff Boissoneault, Jason G. Craggs, Song Lai & Michael E. Robinson (2018) Task related cerebral blood flow changes of patients with chronic fatigue syndrome: an arterial spin labeling study, Fatigue: Biomedicine, Health & Behavior, DOI: 10.1080/21641846.2018.1453919

Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome

We recently reported in Gut that non-coeliac wheat sensitivity (NCWS) is associated with a state of systemic immune activation in conjunction with a compromised intestinal epithelium.1 Patients with NCWS experience GI symptoms, most commonly including abdominal pain and bloating, as well as extraintestinal symptoms, among which fatigue, headache and cognitive difficulties feature prominently.1 2 A principal component analysis of the generated data from our study, including markers of antibody reactivity to wheat gluten, intestinal cell damage and systemic innate and adaptive immune responses to microbial components, found clustering of the patients and controls into discernible groups and demonstrated the potential utility of the identified biomarkers for identifying patients with NCWS.1

Extreme fatigue, in particular one that does not improve with rest, is a hallmark of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).3 Immune system abnormalities have been found to be associated with symptoms in a substantial number of patients with ME/CFS.4 5 Furthermore, many patients complain of GI symptoms of unknown aetiology.6–8 We considered whether a subset of patients with ME/CFS may exhibit serologic markers associated with NCWS, which might explain some of the corresponding symptoms. We screened serum samples from 131 patients with ME/CFS and 86 healthy controls (table 1), recruited as previously described,9 for the same markers as those in the above-mentioned study on NCWS.1 Questionnaires were used to assess GI symptoms within the past 6 months, including abdominal pain, bloating and nausea. Severity of individual symptoms was scored from 1 to 5 (1=absent; 2=mild; 3=moderate; 4=severe; 5=very severe), and a total score, based on the sum of individual symptom scores, was calculated for each subject.

Read full article HERE.

Source: Melanie Uhde, Alyssa C Indart, Xuechen B Yu, Sophie S Jang, Roberto De Giorgio, Peter H R Green, Umberto Volta, Suzanne D Vernon, Armin Alaedini. Markers of non-coeliac wheat sensitivity in patients with myalgic encephalomyelitis/chronic fatigue syndrome. http://dx.doi.org/10.1136/gutjnl-2018-316133

Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT

Abstract:

Background: The PACE trial was a well-powered randomised trial designed to examine the efficacy of graded exercise therapy (GET) and cognitive behavioural therapy (CBT) for chronic fatigue syndrome. Reports concluded that both treatments were moderately effective, each leading to recovery in over a fifth of patients. However, the reported analyses did not consistently follow the procedures set out in the published protocol, and it is unclear whether the conclusions are fully justified by the evidence.

Methods: Here, we present results based on the original protocol-specified procedures. Data from a recent Freedom of Information request enabled us to closely approximate these procedures. We also evaluate the conclusions from the trial as a whole.

Results: On the original protocol-specified primary outcome measure – overall improvement rates – there was a significant effect of treatment group. However, the groups receiving CBT or GET did not significantly outperform the Control group after correcting for the number of comparisons specified in the trial protocol. Also, rates of recovery were consistently low and not significantly different across treatment groups. Finally, on secondary measures, significant effects were almost entirely confined to self-report measures. These effects did not endure beyond two years.

Conclusions: These findings raise serious concerns about the robustness of the claims made about the efficacy of CBT and GET. The modest treatment effects obtained on self-report measures in the PACE trial do not exceed what could be reasonably accounted for by participant reporting biases.

Source: Carolyn E. Wilshire, Tom Kindlon, Robert Courtney, Alem Matthees, David Tuller, Keith Geraghty and Bruce Levin. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC PsychologyBMC series. Received: 29 May 2017; Accepted: 22 February 2018; Published: 22 March 2018.  https://doi.org/10.1186/s40359-018-0218-3 (Full article) © The Author(s) 2018.

Help Desperate Patients Get Crisis Support!

 

AMMES’ Crowdrise campaign to raise funds for emergency aid for patients in financial crisis was successful! We raised $10,000 in online donations and in checks sent separately by donors. AMMES has already begun processing applications to the fund. A big THANK YOU to everyone who donated!

So any patients are disabled and unable to work. Assistance at the right time can go a long way. Our mission is to help patients and their families in practical ways. This is one of them.

This is the description that appeared on Crowdrise. The campaign ended on May 11, 2018. You can still donate to this fund HERE.

“Between 836,000 and 2.5 million Americans suffer from ME/CFS. One quarter of these patients are severely ill, and are either bedbound or housebound. Severely ill patients are unable to work, and many are denied disability. The financial crisis generated by a loss of income coupled with rising costs of medical care can force patients to forego necessary care and medication. In some cases, patients may even lose their homes and end up living in cars. In order to assist patients in need, AMMES is setting up a crisis fund to provide one-time grants to patients for specific needs. The funds can be used to purchase a wheelchair, pay a medical bill, hire home care, secure adequate housing, and other basic needs. All applicants will be required to provide written medical confirmation of their diagnosis, proof of financial need, and document the specific purpose of the grant. Where possible, a phone interview will be conducted. (Some severely ill patients cannot speak.) Any patient within the United States and its territories is eligible.”