Immune dysregulation in CFS similar to autoimmune disorders


Perturbations in immune processes are a hallmark of a number of autoimmune and inflammatory disorders.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is an inflammatory disorder with possible autoimmune correlates, characterized by reduced NK cell activity, elevations in regulatory T cells (Tregs) and dysregulation in cytokine levels.

The purpose of this article is to examine innate and adaptive immune cell phenotypes and functional characteristics that have not been previously examined in CFS/ME patients.

Thirty patients with CFS/ME and 25 non-fatigued controls were recruited for this study.

Whole blood samples were collected from all participants for the assessment of cell phenotypes, functional properties, receptors, adhesion molecules, antigens and intracellular proteins using flow cytometric protocols.

The cells investigated included NK cells, dendritic cells, neutrophils, B cells, T cells, gamma deltaT cells and Tregs.

Significant changes were observed in B-cell subsets, Tregs, CD4+CD73+CD39+ T cells, cytotoxic activity, granzyme B, neutrophil antigens, TNF-alfa – and IFN-gamma in the CFS/ME patients in comparison with the non-fatigued controls.

Alterations in B cells, Tregs, NK cells and neutrophils suggest significant impairments in immune regulation in CFS/ME and these may have similarities to a number of autoimmune disorders.

Role of adaptive and innate immune cells in chronic fatigue syndrome/myalgic encephalomyelitis by EW Brenu et al in International Immunology, 19 January 2014.[Epub ahead of print]

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Immune dysfunction worse in severe CFS patients


Objective: Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a disabling illness, characterized by persistent, debilitating fatigue and a multitude of symptoms. Immunological alterations are prominent in CFS/ME cases, however little is known about the relationship between CFS/ME severity and the extent of immunological dysfunction. The purpose of this study was to assess innate and adaptive immune cell phenotypes and function of two groups of CFS/ME patients, bedridden (severe) and mobile (moderate).

Methods: CFS/ME participants were defined using the Centres for Disease Prevention and Control (1994 CDC) Criteria for CFS/ME.

Participants were grouped into healthy controls (n=22, age=40.14 ± 2.38), moderate/mobile (n=23; age=42.52 ± 2.63) and severe/bedridden (n=18; age=39.56 ± 1.51) CFS/ME patients. Flow cytometric protocols were used to examine neutrophil, monocyte, dendritic cells (DCs), iNKT, Treg, B, gamma delta and CD8+ T cell phenotypes, NK cytotoxic activity and receptors.

Results: The present data found that CFS/ME patients demonstrated significant decreases in NK cytotoxic activity, transitional and regulatory B cells, gamma delta 1T cells, KIR2DL1/DS1, CD94+ and KIR2DL2/L3.

Significant increases in CD56-CD16+NKs, CD56dimCD16- and CD56brightCD16-/dim NKs, DCs, iNKT phenotypes, memory and naive B cells were also shown in CFS/ME participants. Severe CFS/ME patients demonstrated increased CD14-CD16+ DCs, memory and naïve B cells, total iNKT, iNKT cell and NK phenotypes compared to moderate CFS/ME patients.

Conclusion: This study is the first to determine alterations in NK, iNKT, B, DC and gamma delta T cell phenotypes in both moderate and severe CFS/ME patients. Immunological alterations are present in innate and adaptive immune cells and sometimes, immune deregulation appears worse in CFS/ME patients with more severe symptoms. It may be appropriate for CFS/ME patient severity subgroups to be distinguished in both clinical and research settings to extricate further immunological pathologies that may not have been previously reported.

Analysis of the relationship between immune dysfunction and symptom severity in patients with CFS/ME, by Sharni Lee Hardcastle et al in J Clin Cell Immunol 5: 190.

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Adverse effects of antidepressants greater than reported



In the context of rapidly increasing antidepressant (AD) use internationally, and recent reviews raising concerns about efficacy and adverse effects, this study aimed to survey the largest sample of AD recipients to date.


An online questionnaire about experiences with, and beliefs about, antidepressants was completed by 1829 adults who had been prescribed antidepressants in the last five years (53% were first prescribed them between 2000 and 2009, and 52% reported taking them for more than three years).


Eight of the 20 adverse effects studied were reported by over half the participants; most frequently Sexual Difficulties (62%) and Feeling Emotionally Numb (60%). Percentages for other effects included: Feeling Not Like Myself – 52%, Reduction In Positive Feelings – 42%, Caring Less About Others – 39%, Suicidality – 39% and Withdrawal Effects – 55%. Total Adverse Effect scores were related to younger age, lower education and income, and type of antidepressant, but not to level of depression prior to taking antidepressants.


The adverse effects of antidepressants may be more frequent than previously reported, and include emotional and interpersonal effects.

Adverse emotional and interpersonal effects reported by 1829 New Zealanders while taking antidepressants, by John Read, Claire Cartwright, Kerry Gibson in Psychiatry Research, 2014

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Correction is a full-featured social network for all ages (not for 40-and-under patients, as previously reported) with neuro-immune illness (ME/CFS, Chronic Lyme Disease, Fibromyalgia, Atypical MS, MCS, mold illness)

It aims to:

  • Connect patients that have the most medical details in common, so they can share their treatment experiences with each other
  • Help patients visualize health changes over time using the comprehensive health tracker.
  • Collaborate with researchers to find answers for our illness.


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Exercise intolerance in CFS caused by low oxygen extraction


Background: The insufficient metabolic adaptation to exercise in Chronic Fatigue Syndrome (CFS) is still being debated and poorly understood.

Methods: We analysed the cardiopulmonary exercise tests of CFS patients, idiopathic chronic fatigue (CFI) patients and healthy visitors. Continuous non-invasive measurement of the cardiac output by Nexfin ® (BMEYE B.V. Amsterdam, the Netherlands) was added to the cardiopulmonary exercise tests. The peak oxygen extraction by muscle cells and the increase of cardiac output relative to the increase of oxygen uptake (ΔQ’/ΔV’O2) were measured, calculated from the cardiac output and the oxygen uptake during incremental exercise.

Results: The peak oxygen extraction by muscle cells was 10.83 ± 2.80 ml/100ml in 178 CFS women, 11.62 ± 2.90 ml/100 ml in 172 CFI, and 13.45 ± 2.72 ml/100 ml in 11 healthy women (ANOVA:P=0.001), 13.66 ± 3.31 ml/100 ml in 25 CFS men, 14.63 ± 4.38 ml/100 ml in 51 CFI, and 19.52 ± 6.53 ml/100 ml in 7 healthy men (ANOVA:P=0.008).

TheΔQ’/ΔV’O2 was > 6 L/L (normalΔQ’/ΔV’O2≈5 L/L) in 70% of the patients and in 22% of the healthy group.

Conclusion: Low oxygen uptake by muscle cells causes exercise intolerance in a majority of CFS patients, indicating insufficient metabolic adaptation to incremental exercise. The high increase of the cardiac output relative to the increase of oxygen uptake argues against deconditioning as a cause for physical impairment in these patients.

Decreased oxygen extraction during cardiopulmonary exercise test in patients with chronic fatigue syndrome by Ruud CW Vermeulen and Ineke WG Vermeulen van Eck in Journal of Translational Medicine 2014,12:20

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Medications cause 70% of dry eyes, mouth etc. in CFS

Chronic fatigue syndrome (CFS) is a heterogeneous and multisystemic disorder of unknown pathogenesis and etiology. It is characterized by prolonged generalized and abnormal fatigue post-exercise (98%), recurrent headache (90%) and problems of concentration and memory (85%) that have lasted for at least 6 months. It is accompanied by such other symptoms as tender lymph nodes (80%), musculoskeletal pain (75%) and psychiatric problems (65%). The prevalence of CFS is estimated to be between 0.5 and 2.5%, predominantly in women (4:1).

Many patients with CFS also complain of sicca symptoms [dryness of the eyes, mouth and other body parts] in up to 30–87%, and are more likely to have thyroid disorder and sleep disruption; that may suggest an underlying role of the immune system in these patients.

Primary Sjögren’ syndrome (PSS) is a systemic autoimmune disease, that presents chronic exocrine glands hypofunction leading to xerostomia and/or xerophthalmia, and extraglandular involvement, of which autoimmune hypothyroidism (AIHT) is the most common autoimmune disease developed.

Patients with PSS, also experience CFS-like musculoskeletal and neurocognitive symp-toms more than 50%, and the two disorders share some similar immunologic defects.

The purpose of this study was to determine the causality of sicca symptoms in 199 consecutive patients diagnosed as having CFS, and the possible association with PSS, although few studies that have examined this association (between 2010 and 2012 in our chronic fatigue unit of Joan XXIII University Hospital) criteria of 1994.

One hundred sixty-seven patients (84%) were women. The age of onset of symptomswas 41 ± 10 years. Mucosal sicca symptoms were complained by160 patients (80.4%): 11/160 (6.8%) patients were diagnosed with PSS (9 patients were incomplete PSS and 2 patients were complete PSS by positive lower lip biopsy that had MSG focusscore >1, using the American-European criteria 20025). 110/160patients (68.75%) were mainly due to xerogenic medications.

Severe obstructive sleep apnea syndrome (OSAS) was diagnosed in 6/160 patients (3.75%) (according to the American Academy of Sleep Medicine, Chicago Criteria 1999) by polysomnographicanalysis. Thirty-eight (23.75%) patients were seropositive for thyroperoxidase antibody (TPO-Ab) and/or thyroglobulin antibody (Tg-Ab) (of these patients 33/160 (20.6%) were diagnosed as having AIHT), 15 (10.2%) had a positive antinuclear antibody (ANA) assay (titer count >1:160), and 5 (3.5%) had a positive parietal cell antibody (titer count >1:160). All were seronegative for anti-Ro/SS-A and anti-La/SS-B. In previous studies mucosal sicca symptoms were described as one of the common clinical manifestations of CFS as seen in our series.

Nishikai et al. and Sirois et al. had found sicca symptoms in 73% and 52% of their series respectively. As possible causes in our study, we determined that the prevalence of sicca symptoms (especially xerostomia) induced by psychotropic medications with anticholinergic side effects (amitriptyline, clonazepam, etc.) was high as described in several studies. Drugs with anticholinergic actions decrease salivary gland secretion by neurochemical blockade. It is usually dose related and reversible when medication is discontinued.

We also found a group of CFS patients with sicca symptoms that may be attributed to AIHT and OSAS.This suggests that these two disorders share common pathophysiological features with CFS. Interestingly, in patients with OSAS,CFS symptoms were improved by using continuous nasal positive airway pressure (CPAP).

Any potential relationship between CFS and PSS is complicated by the lack of a sensitive test or agreement regarding the diagnostic criteria for PSS.

Nishikai et al. examined a group of 75 seronegative patients diagnosed with CFS and found that 22 (29%) met the European criteria 1993 for PSS.6 Sirois et al. also examined 25 patients diagnosed with CFS and found that 32% met diagnostic criteria for PSS according to the European criteria 1993.

These results were not similar to ours in the study we present (11 patients if we included patients with incomplete PSS) as we described previously (Table 1). In searching of causes of this poor association, several considerations have to be taken into account in our study.

1st, in our study we used the 2002 criteria that require mandatory: (1) a positive salivary gland biopsy (only done in 5 patients), or (2) the presence of antibodies to SSA/Ro and/or toSS-B/La (negative in all patients). The serological item was also met in the 1993 criteria (used by Nishikai et al. and Sirois et al.,6,7) but only if a test for rheumatoid factor or ANA was positive. This condi-tion has probably increased the prevalence of PSS in their studies.

2nd, symptoms or signs of PSS do not always begin at the same time and that patients with incomplete SS maybe will meet the diagnostic criteria 2002 at some point in the future.

In summary, in our study about 70% of CFS patients with sicca syndrome are related to be drug-induced. Therefore, xerogenic medications, as possible cause, must be excluded. However, we recommend that patients who have been diagnosed with CFS and manifest mucosal sicca symptoms should be also screened for SS, AIHT and/or OSAS; and should be regarded as a comorbidity of CFS, not a diagnostic exclusion criterion.

Etiology of sicca syndrome in a consecutive series of 199 patients with chronic fatigue syndrome, by R Qanneta et al, in Reumatol Clin. 2013 (letter)

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Sleep solutions for disabled children: online events 11th, 12th 18th, 19th March

Children need good sleep as much as they need good food. Being tired affects your whole family’s mood, health, learning and behaviour, at school and work.

If this sounds like you, don’t suffer alone. This March, get help from Scope’s Sleep Solutions team and their bite-sized training and support. The team has years of experience working with families of disabled children and those with additional needs. Ask questions, pick up tips and find out more about what support is available.

Sleep Solutions: get involved in Scope’s online events 11th, 12th, 18th, 19th March

According to a Contact a Family survey, over 70% of disabled children have sleep problems.

Sleep deprivation in children can affect their mood, concentration levels, behaviour, health, learning… the list is endless! A child with sleep problems will also have huge impacts on parents and siblings – sleep is crucial for everybody’s health and well-being.

The most common sleep problems children experience are:

  • Problems falling asleep
  • Problems staying asleep
  • Waking too early in the morning

Scope can support families and professionals to help to resolve sleep difficulties by offering:

  • Tips for tackling sleep problems
  • Sleepy foods
  • Average sleep needs
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State of caring survey 2014

Carers UK’s annual State of Caring survey looks into the impact that caring for ill, frail or disabled relatives can have on carers’ finances, health and ability to live their own lives. By sharing your views and experiences, you can help them expose how hard it can be to care and and what needs to change to make carers’ lives better.

The survey should take between 15 and 30 minutes to complete  depending on the detail of information you wish to provide and will bring together and update a variety of different pieces of research Carers UK has done in previous years to get an up to date picture of caring in 2014.

If you have had a particularly good experience and received support that has made a real difference to you, or have had particularly bad experiences, they would like to know.

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Arolwg cefnogaeth i ofalwyr Caerdydd a’r Fro

Mae Bwrdd Iechyd Prifysgol Caerdydd a’r Fro, Cyngor Caerdydd a Chyngor Bro Morgannwg yn cydweithio i gael adborth gan ofalwyr sy’n byw yng Nghaerdydd neu Fro Morgannwg, er mwyn deall pa mor dda yr ydym yn eich cefnogi ac er mwyn ein helpu ni i wella. Byddem yn ddiolchgar pe baech yn llenwi’r arolwg byr hwn, gan fod eich barn yn bwysig iawn i ni.

Pam ddylech chi gymryd rhan?

Gofalwr yw rhywun sy’n edrych ar ôl perthynas, ffrind neu gymydog sy’n methu ymdopi heb gymorth oherwydd eu bod yn oedrannus, yn anabl oherwydd iechyd corfforol neu iechyd meddwl, problem gyffuriau neu alcohol neu sydd â salwch hirdymor. Mae’r gofal a roddir ganddynt yn ddi-dâl. Os yw hyn yn eich disgrifio chi, a fyddech cystal â llenwi’r arolwg hwn.



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Bwysig gwahaniaethu ME (gyda Post-exertional malaise) o CFS


Myalgic Encephalomyelitis (ME) was identified as a new clinical entity in 1959 and has been acknowledged as a disease of the central nervous system/neurological disease by the World Health Organisation since 1969. Cognitive impairment, (muscle) weakness, circulatory disturbances, marked variability of symptoms, and, above all, post-exertional malaise: a long-lasting increase of symptoms after minor exertion, are distinctive symptoms of ME.

Chronic Fatigue Syndrome (CFS) was introduced in 1988 and was redefined into clinically evaluated, unexplained (persistent or relapsing) chronic fatigue, accompanied by at least four out of a list of eight symptoms, e.g. headaches and unrefreshing sleep, in 1994.

Although the labels are used interchangeably, ME and CFS define distinct diagnostic entities. Post-exertional malaise and cognitive deficits e.g. are not mandatory for the diagnosis CFS, while obligatory for the diagnosis ME. “Fatigue” is not obligatory for the diagnosis ME.

Since fatigue and other symptoms are subjective and ambiguous, research has been hampered. Despite this and other methodological issues, research has observed specific abnormalities in ME/CFS repetitively, e.g. immunological abnormalities, oxidative and nitrosative stress, neurological anomalies, circulatory deficits and mitochondrial dysfunction.

However, to improve future research standards and patient care, it is crucial that patients with post-exertional malaise (ME) and patients without this odd phenomenon are acknowledged as separate clinical entities, that the diagnosis of ME and CFS in research and clinical practice is based upon accurate criteria and an objective assessment of characteristic symptoms, as much as possible, that well-defined clinical and biological subgroups of ME and CFS patients are investigated in more detail, and that patients are monitored before, during and after interventions with objective measures and biomarkers.

Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS): The essence of objective assessment, accurate diagnosis, and acknowledging biological and clinical subgroups, by Frank N.M. Twisk in Front. Physiol.5:109

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