CD24 expression & B cell maturation shows a novel link with energy metabolism: potential implications for patients with ME/CFS

Posted on 11/21/2018 by wames

CD24 expression and B cell maturation shows a novel link with energy metabolism: potential implications for patients with Myalgic Encephalomyelitis / Chronic Fatigue Syndrome , by Fane K. Mensah, Christopher W Armstrong, Venkat Reddy, Amolak S Bansal, Saul Berkovitz, Maria Leandro and Geraldine Cambridge in Front. Immunol. 22 Oct 2018

Research abstract:

CD24 expression on pro-B cells plays a role in B cell selection and development in the bone marrow. We previously detected higher CD24 expression and frequency within IgD+ naïve and memory B cells in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) compared with age-matched healthy controls (HC). Here, we investigated the relationship between CD24 expression and B cell maturation.

In vitro stimulation of isolated B cells in response to conventional agonists were used to follow the dynamics of CD24 positivity during proliferation and differentiation (or maturation). The relationship between CD24 expression to cycles of proliferation and metabolism in purified B cells from HC was also investigated using phospho-flow (phosphorylation of AMPK-pAMPK), 1proton nuclear magnetic resonance and Mitotracker Far-red (Mitochondrial mass-MM).

In vitro, in the absence of stimulation, there was an increased percentage of CD24+ viable B cells in ME/CFS patients compared to HC (p< 0.05) following 5 days culture. Following stimulation with B cell agonists, percentage of CD24+B cells in both naïve and memory B cell populations decreased. p< 0.01). There was a negative relationship between percentage of CD24+B cells with MM (R2=0.76; p< 0.01), which was subsequently lost over sequential cycles of proliferation. There was a significant correlation between CD24 expression on B cells and the usage of glucose and secretion of lactate in vitro. Short term ligation of the B cell receptor with anti-IgM antibody significantly reduced the viability of CD24+ memory B cells compared to those cross-linked by anti-IgD or anti-IgG antibody. A clear difference was found between naïve and memory B cells with respect to CD24 expression and pAMPK, most notably a strong positive association in IgD+IgM+ memory B cells. In vitro findings confirmed dysregulation of CD24-expressing B cells from ME/CFS patients previously suggested by immunophenotype studies of B cells from peripheral blood.

CD24-negative B cells underwent productive proliferation whereas CD24+ B cells were either unresponsive or susceptible to cell death upon BCR-engagement alone. We suggest that CD24 expression may reflect variations in energy metabolism on different B cell subsets.

Cort Johnson discusses this research on the Simmaron Research blog: Immune Study Adds to Evidence Of Body-Wide Problems With Energy Production in Chronic Fatigue Syndrome (ME/CFS)

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Workwell’s two-day exercise tests & breaking the deconditioning dilemma in ME/CFS

Posted on 11/21/2018 by wames

Workwell’s two-day exercise tests and breaking the deconditioning dilemma in Chronic Fatigue Syndrome (ME/CFS) by Cort Johnson in Health rising blog, 19 Nov 2018

The first word in the first sentence of the paper says it all:

“Concise methodological directions for administration of serial cardiopulmonary exercise testing (CPET) are needed for testing of patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).”

Why concise? Because Workwell asserts that in the universe of diseases known to man Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is so different when it comes to exercise that it needs a place all it’s own. It needs it’s own concise methodology, and above all it needs to be understood differently.

This methodology paper, then, is an attempt by the exercise physiologists at Workwell (Staci Stevens, Mark Van Ness, Chris Snell, Jared Stevens) and Betsy Keller to spread the word that something very different, something perhaps even unique in the annals of medicine, is occurring in people with chronic fatigue syndrome when they exercise.

Someone, it seems, is listening. This dry, seemingly obscure methodology paper (“Cardiopulmonary Exercise Test Methodology for Assessing Exertion Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome“) has proven to be a surprise hit. In the two months since its publication it’s been viewed by over 7400 people spread across the globe…

It’s a remarkable fact that even people with disabling diseases can exercise to exhaustion two days in a row without effecting their ability to produce energy

Workwell has been giving two-day CPETs for years. I asked Staci if the drop in energy production seen in an exercise test given one day after a previous test was really unique in ME/CFS. Her answer demonstrated just how much we have to learn:

Clinically we have seen patients with more than 30 different fatiguing conditions including POTS and fibromyalgia. ME/CFS is unique but more research is needed to determine ME/CFS CPET subsets and if other conditions have abnormal test 2 responses.

Our clinical patients often have comorbid conditions, so this makes it more difficult to sort out. That said, several distinct subsets of abnormal responses are emerging. We have a case series on this very topic comparing fatiguing conditions with ME/CFS which will be published soon.

Read more about:

  • POTS & deconditioning
  • Workwell’s plans for larger exercise tests
  • A Guide to Giving a Two-Day Exercise Test in ME/CFS – The Methodology Section
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Associations between clinical symptoms, plasma norepinephrine & deregulated immune gene networks in subgroups of adolescents with CFS

Posted on 11/19/2018 by wames

Associations between clinical symptoms, plasma norepinephrine and deregulated immune gene networks in subgroups of adolescent with Chronic Fatigue Syndrome, by Chinh Bkrong Nguyen, Surendra Kumar, Manuela Zucknick, Vessela N Kristensen, Johannes Gjerstad, Hilde Nilsen, Vegard BruunWyller, in Brain Behav Immun. 2018 Nov 9. pii: S0889-1591(18)30796-7 [Epub ahead of print]

Highlights:

Research abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is one of the most important causes of disability among adolescents while limited knowledge exists on genetic determinants underlying disease pathophysiology.

METHODS: We analyzed deregulated immune-gene modules using Pathifier software on whole blood gene expression data (29 CFS patients, 18 controls). Deconvolution of immune cell subtypes based on gene expression profile was performed using CIBERSORT. Supervised consensus clustering on pathway deregulation score (PDS) was used to define CFS subgroups. Associations between PDS and immune, neuroendocrine/autonomic and clinical markers were examined. The impact of plasma norepinephrine level on clinical markers over time was assessed in a larger cohort (91 patients).

RESULTS: A group of 29 immune-gene sets was shown to differ patients from controls and detect subgroups within CFS. Group 1P (high PDS, low norepinephrine, low naïve CD4+ composition) had strong association with levels of serum C-reactive protein and Transforming Growth Factor-beta. Group 2P (low PDS, high norepinephrine, high naïve CD4+composition) had strong associations with neuroendocrine/autonomic markers. The corresponding plasma norepinephrine level delineated 91 patients into two subgroups with significant differences in fatigue score.

CONCLUSION: We identified 29 immune-gene sets linked to plasma norepinephrine level that could delineate CFS subgroups. Plasma norepinephrine stratification revealed that lower levels of norepinephrine were associated with higher fatigue. Our data suggests potential involvement of neuro-immune dysregulation and genetic stratification in CFS.

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Shop this Christmas on Amazon Smile & raise funds free for WAMES

Posted on 11/16/2018 by wames

You shop. Amazon gives, with a smile.

Amazon will donate 0.5% of the net purchase price of eligible purchases to the charitable organisation of your choice.

Choose WAMES!

AmazonSmile is the same Amazon you know. Same products, same prices, same service.

  • Go to https://smile.amazon.co.uk
  • Sign in to your account or register a new account
  • Name WAMES as the charity you wish to support
  • Now shop – Amazon will send money to WAMES
  • Or go directly to support WAMES

Remember – always shop through https://smile.amazon.co.uk

Choose WAMES now and help keep WAMES on the campaign trail!

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The abnormal cardiac index & stroke volume index changes during a normal tilt table test in ME/CFS patients… are not related to deconditioning

Posted on 11/16/2018 by wames

The abnormal cardiac index and stroke volume index changes during a normal tilt table test in ME/CFS patients compared to healthy volunteers, are not related to deconditioning, by C (Linda) MC van Campen, Frans C. Visser in Journal of Thrombosis and Circulation, 7 November, 2018

Research abstract: 

1.1    Background. A small study in ME/CFS (Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome) patients undergoing tilt testing, showed that, despite a normal tilt test, stroke volumes and cardiac output were lower than in healthy volunteers. Moreover, it was suggested that this difference was related to deconditioning of patients.

Aim of the study. We performed table testing in 150 ME/CFS patients. Stroke volumes and cardiac output were related to the severity of the disease.

1.2    Methods and results. In the patients the severity of the disease was clinically evaluated according to the ME criteria and scored as mild, moderate or severe disease. In a subgroup of 109 patients this clinical diagnosis was confirmed by the physical functioning score of the Rand-36 questionnaire. Significantly lower physical functioning scores (indicating worse functioning) were observed in the more severely affected patients. Stroke Volume Index (SVI) and Cardiac Index (CI) were measured by suprasternal aortic Doppler imaging in the supine position, prior to the tilt, and twice during the tilt. Thirty-seven healthy volunteers underwent the same tilt protocol. In all patients and all healthy volunteers, a normal heart rate and blood pressure response was observed during the tilt. The decreases in SVI and CI during the tilt was significantly larger in patients compared to the SVI and CI decrease in HV. The decrease in SVI and CI were similar and not significantly different between the mild, moderate, and severe ME groups.

1.3    Conclusions. During a normal tilt table test decreases in SVI and CI decrease are significantly greater in ME/CFS patients than in HV, consistent with previous work. The absence of differences between patients with mild, moderate, and severe ME/CFS suggests that the decreases in stroke volumes and cardiac output are not related to deconditioning. Other factors like decreased blood volumes and autonomic dysfunction may cause this difference in the hemodynamic response between ME/CFS patients and HV.

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Low omega-3 index & polyunsaturated fatty acid status in patients with CFS/ME

Posted on 11/15/2018 by wames

Low omega-3 index and polyunsaturated fatty acid status in patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis, by Jesús Castro-Marrero, Joan Carles Domingo, Alba Martinez-Martinez, José Alegre, Clemens von Schacky in Prostaglandins, Leukotrienes and Essential Fatty Acids (PLEFA) [Published online: November 9, 2018]

Highlights:

  • Erythrocyte omega-3 index (5.75%) and n-3 PUFA levels are low in individuals with CFS/ME.
  • The erythrocyte omega-3 index may be a useful biomarker of overall health, but cut-off points need be validated in the Spanish CFS/ME population.
  • This study suggests that low EPA + DHA levels may be a risk factor for poor cardiovascular health and pro-inflammatory status in CFS/ME. Understanding the role of omega-3 PUFAs and immunometabolism should be the next step.
  • Further studies of omega-3 fatty acid supplementation in CFS/ME are warranted.

Research abstract:

Background:
Several studies have suggested that low levels of omega-3 fatty acids (n-3 PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with cardiovascular risk, major depression, sleep problems, inflammation and other health-related issues. So far, however, erythrocyte PUFA status in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) has not been established. This study aimed to determine whether n-3 PUFA content and omega-3 index are associated with measures in CFS/ME patients.

Patients and Methods:
PUFA levels and omega-3 index were measured in 31 Spanish CFS/ME patients using the HS-Omega-3 Index® method. Demographic and clinical characteristics and self-reported outcome measures were also recorded.

Results:
A low mean omega-3 index (5.75%) was observed in 92.6% of the sample. Omega-3 index was inversely correlated with the AA/EPA ratio (p= 0.00002) and the BMI (p= 0.0106). In contrast, the AA/EPA ratio was positively associated with the BMI (p= 0.0038). No association for FIS-40 and PSQI measures was found (p> 0.05).

Conclusion:
The low omega-3 index found in our CFS/ME patients may indicate increased risks for cardiovascular health, which should be further investigated. A low omega-3 index also suggests a pro-inflammatory state in these patients. Attempts should be made to increase the omega-3 index in CFS/ME patients, based on intervention trials assessing a potential therapeutic value.

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CFS: Suggestions for a nutritional treatment in the therapeutic approach

Posted on 11/14/2018 by wames

Chronic fatigue syndrome (CFS): Suggestions for a nutritional treatment in the therapeutic approach, by Geir Bjørklund, Maryam Dadar, Joeri J Pen, Salvatore Chirumbolo, Jan Aaset in Biomedicine & Pharmacotherapy Vol 109, Jan 2019, Pp 1000-1007

Review abstract:
Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported.

In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l-carnitine, l-tryptophan, essential fatty acids, and coenzyme Q10) appear to be important in the severity and exacerbation of CFS symptoms.

This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients.

Excerpt:

A meta-analysis with 27 studies concludes that there are still few data to provide a promising hypothesis for the effective role of mineral and vitamin supplementation in the CFS pathophysiology and therapy. Current studies on minerals and vitamins in CFS patients need large population-based and age-matched prospective research, as well as well-observed interventional studies in CFS patients, to achieve more awareness in the efficacy of minerals and vitamins in the CFS pathophysiology. According to this analysis, vitamin A and vitamin E are promising vitamins that need further examination.

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Hand grip strength as a clinical biomarker for ME/CFS & disease severity

Posted on 11/13/2018 by wames

Hand grip strength as a clinical biomarker for ME/CFS and disease severity, by Luis C Nacul, Kathleen Mudie, Caroline Kingdon, Taane G Clark, Eliana M Lacerda in Frontiers in Neurology, 5 Nov 2018 [Preprint]

Research abstract:

Background:
The diagnosis of myalgic encephalomyelitis (ME/CFS) in research and clinical practice has largely relied on clinical history, which can be subjective in nature. Clinical signs are often subtle, overlap with other conditions, and are not formally included as part of diagnostic workup. The characterisation of clinical signs and biomarkers is needed for better diagnosis and classification of patients and to monitor treatment response.

Hand grip strength (HGS) has been used as an objective measure of muscle strength and fatigue, which is a primary symptom of ME/CFS. We assessed the potential usefulness of HGS as a diagnostic marker in ME/CFS.

Methods:
We compared HGS measurements from participants in the UK ME/CFS Biobank, with groups consisting of people with ME/CFS of differing severity (n=272), healthy (n=136), multiple sclerosis (n=76) controls, and others with chronic fatigue not meeting the diagnosis of ME/CFS (n=37). We correlated the maximum and minimum of, and differences between, 3 repeated HGS measurements with parameters of disease severity, including fatigue and pain analog scales, and physical and mental component summaries from the SF-36v2TM questionnaire across recruitment groups.

Results:
HGS indicators were associated with having ME/CFS, with magnitudes of association stronger in severely affected than in mild/moderately affected patients. Compared with healthy controls, being severely affected was associated with a reduction in minimum HGS of 15.3kg (95%CI 19.3-11.3; p<0.001), while being mild/moderately affected was associated with a 10.5kg (95%CI 13.2-7.8; p<0.001) reduction. The association persisted after adjusting for age, sex and body mass index. ME/CFS cases also showed lower values of maximum HGS and significant drops in values from the first to second and third trials, compared to other study groups. There were significant correlations between HGS indicators and clinical parameters of disease severity, including fatigue analog scale
(Spearman’s Rho= -0.40, p<0.001), pain analog scale (Rho=-0.38, p<0.001), and physical component summary (Rho=0.42, p<0.001).

Discussion:
HGS is markedly reduced in ME/CFS, particularly in patients with more severe disease, and may indicate muscle and fatigue related symptoms.

HGS is a potential diagnostic tool in ME/CFS, and could also be used to enhance patient phenotyping and as an outcome measure following interventions.

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Understanding ME & CFS symptoms in children – take part in research project!

Posted on 11/09/2018 by wames

Symptomatology of pediatric ME & CFS – research project

The Center for Community Research at DePaul University in the USA, led by Prof Leonard Jason says:

There is currently little research on children with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Through this study, we hope to learn more about the symptoms and experiences of children who are living with ME and CFS.

We are requesting responses from children (ages 5-17) with ME and CFS and their parents. Parents will complete the first set of questionnaires (30 minutes), and children will complete the next (final) set of questionnaires (30 minutes).

Take the online survey

We recognize that this survey contains many questions, and we are extremely grateful for the time and effort you devote to this study.  You do not need to complete all of the questions at one time; you may save and return to complete the survey later as many times as necessary.

Contact Madison Sunnquist  msunnqui@depaul.edu with any questions, or if you would like to be contacted about future research opportunities related to pediatric ME and CFS.

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Internet-delivered cognitive behaviour therapy for chronic health conditions: a systematic review & meta-analysis

Posted on 11/06/2018 by wames

Internet-delivered cognitive behaviour therapy for chronic health conditions: a systematic review and meta-analysis, by Swati Mehta, Vanessa A Peynenburg, Heather D Hadjistavropoulos in Journal of Behavioral Medicine, 1 November 2018 [Preprint]

Review abstract:

This systematic review and meta-analysis aims to evaluate the effectiveness of internet-delivered cognitive behavioural therapy (ICBT) on anxiety and depression among persons with chronic health conditions.

A systematic database search was conducted of MEDLINE, CINAHL, PsycInfo,
EMBASE, and Cochrane for relevant studies published from 1990 to September 2018. A study was included if the following criteria were met:
(1) randomized controlled trial involving an ICBT intervention;

(2) participants experienced a chronic health condition;

(3) participants >=18 years of age; and

(4) effects of ICBT on anxiety and/or depression were reported.

The Cochrane Risk of Bias tool was used to assess the risk of bias on the included studies. Pooled analysis was conducted on the primary and condition specific secondary outcomes. Twenty-five studies met inclusion criteria and investigated the following chronic health conditions: tinnitus (n = 6), fibromyalgia (n = 3), pain (n = 7), rheumatoid arthritis (n = 3), cardiovascular disease (n = 2), diabetes (n = 1), cancer (n = 1), heterogeneous chronic disease population (n = 1), and spinal cord injury (n = 1). Pooled analysis demonstrated small effects of ICBT in improving anxiety and depression.

Moderate effects of therapist-guided approach were seen for depression and anxiety outcomes; while, self-guided approaches resulted in small effects for depression and moderate effects in anxiety outcomes. ICBT shows promise as an alternative to traditional face-to-face interventions among persons with chronic health conditions. Future research on long-term effects of ICBT for individuals with chronic health conditions is needed.

 

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