Chronic mild to moderate fatigue is also called chronic idiopathic fatigue. Physicians at best consider psychotherapy for treatment. But most physicians do not view this condition as a real disease.
In contrast, debilitating chronic severe disease has been termed chronic fatigue syndrome (CFS), or if more severe, myalgic encephalopathy (CFS/ME). Meanwhile published metabolic aberrations in CFS/ME suggest estimating these diseases no longer as mere psychiatric diseases. The metabolic results inspire to further exploration of cell stress response mechanisms, which are summarized in this paper.
Interestingly, cell stress responses were tightly linked to vitamin D3 – mediated effects, such as homeostatic regulation of metabolism, energy and redox balance, as well as defense against pathogens and toxins. Specific personality traits, prevalence of indoor activities, latitude and climate predispose to vitamin D3 deficiency, which is supposed to represent a missing link for a comprehensive model of disease progression from mild chronic fatigue to most severe forms.
By diagnosing vitamin D deficiency in early stages of chronic fatigue, the progression to severe and debilitating chronic fatigue may be prevented. In more severe stages of chronic fatigue, such as CFS/ME, resistance against mere vitamin D replenishment seems to be the rule. Some causal mechanisms for this resistance and potential treatment options are shown.
Conclusion:
Scientific insight to the biomolecular mechanisms of cell homeostasis helps to understand and treat all clinically manifestations associated with different stages of chronic fatigue.
Excerpt from conclusion:
Physicians could be stimulated to revise their treatment regimens by omitting all interventions which induce further redox stress and xenobiotic burden. The drug
and chemical intolerances of CFS/ME patients call for only minor dosages of pain and psychoactive substances. Instead, restoration of effective VDR activity should be
targeted. This is assumed to stabilize a SIRT1/Nrf2-driven stress response.
This might be achieved by plant based diets and/or supplementations, such as those recommended by Naviaux et al. [8], and Xiao W 2018 [31], 8/10 including all B vitamins, and by supplements of vitamin D3 and minerals, which include calcium and magnesium,
in particular. Phosphate deficiency through long-standing vitamin D deficiency should be considered as well.
Due to presumed vitamin D3 resistance and to distinct genomic and translational vitamin D3 responses, personalized high doses such as 250 mcg cholecalciferol and up to 2400 mg calcium per day should be applied [57,58]. Careful clinical observations should clarify the potential reversibility of very severe and long-standing CFS/ME stages. In any case, any sort of stressful challenge, such as xenobiotics, drugs, nutrient additions, microwaves, and psychosocial stress, should be avoided as much as possible.
Stories were written in 2019 from caregivers, parents, and spouses, most of whom live with a pwME (person with ME). To protect those in our care, some authors have not used their full names.
Each patient suffers from Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), a neuro-immune disease which affects each person differently, with a great variety of symptoms and a wide spectrum of disease burden. The National Academy of Medicine says ME/CFS is three times more common in women than men (1), and they estimate that 80% of patients have not yet received a diagnosis (2).
Through their experiences caring for loved ones with ME/CFS, these caregivers have anecdotes and requests for future doctors and occupational therapists to assist with servicing their suffering pwMEs.
J., Mother and at-home caregiver of a pwME
Courtney Miller, at-home caregiver and wife of Robert Miller, an ME/CFS patient of 30 years
Elizabeth B. Burlingame, mother and at-home caregiver of a pwME
Cochrane recently amended its exercise review for myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS) in response to an official complaint.
Objective:
To determine if the amended review has addressed the concerns raised about the previous review and if exercise is an effective treatment that restores the ability to work in ME/CFS.
Method:
The authors reviewed the amended Cochrane exercise review and the eight trials in it by paying particular interest to the objective outcomes. We also summarised the recently published review of work rehabilitation and medical retirement for ME/CFS.
Results:
The Cochrane review concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. However, the review did not consider the unreliability of subjective outcomes in non-blinded trials, the objective outcomes which showed that GET is not effective, or the serious flaws of the studies included in the review. These flaws included badly matched control groups, relying on an unreliable fatigue instrument as primary outcome, outcome switching, p-hacking, ignoring evidence of harms, etc. The review did also not take into account that GET does not restore the ability to work.
Conclusion:
GET not only fails to objectively improve function significantly or to restore the ability to work, but it’s also detrimental to the health of≥50% of patients, according to a multitude of patient surveys. Consequently, it should not be recommended.
Excerpts from paper:
5. Conclusion
The recently amended Cochrane exercise review for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) concluded that graded exercise therapy (GET) improves fatigue at the end of treatment compared to no-treatment. Larun et al. also concluded that there is no evidence that GET is safe. However, the review continues to ignore the unreliability of subjective outcomes in non-blinded studies and fails to address other key flaws of the studies in the review. These flaws included:
1) using criteria that also select people who do not have the disease;
2) not excluding patients with a psychiatric or self-limiting illness;
3) badly matched control groups;
4) relying on an unreliable fatigue instrument as primary outcome;
5) not using objective outcomes and/or ignoring them;
6) outcome switching;
7) p-hacking;
8) ignoring evidence of multi-system biological pathologies that can not be explained by their psychological treatment rationale;
9) ignoring evidence of harms.
Analysis of the objective outcomes shows that GET does not lead to clinically significant objective improvement. It also does not lead to improvement of CFS symptoms count or quality of life measurements, which remains lower for those with ME/CFS, than in many other debilitating illnesses.
Only 5% of patients recover. Many patients are unable to work and those who can work, often need a reduction in hours and/or reduction of physical intensity. Unfortunately, GET doesn’t restore the ability to work. Instead, more patients are unable to work and more are reliant on illness benefits after being treated with GET than before treatment with it.
Finally, to use the words of three leading exercise physiologists in the field of ME/CFS, “graded exercise [therapy]…not only fails to improve function, but is detrimental to the health of [ME/CFS] patients and should not be recommended” [106]
3.6 Important factors enabling a return to work
According to a report by NIVEL, the Netherlands Institute for Health Services Research [92], there are a number of important things which enabled ME/CFS patients to (return to) work. For 92%, the most important thing was support in finding the right balance between work and spare time. The second most important thing (84%), was support and cooperation from the employer to enable patients to continue to work. Other important things were the following:
• supplying information about ME/CFS to colleagues and superiors (62%);
• changing tasks (61%);
• reducing the number of hours they had to work (61%);
• more rest periods during working times (60%);
• the availability of a special rest place at work (45%);
• working from home (52%);
• individual support and coaching in general (51%);
• and by an occupational health physician in particular (44%);
• adjustments to working conditions (furniture, physical aids) (38%);
• and a regulation or provision for commuting to work (36%).
Diminished cardiopulmonary exercise test (CPET) performance indicates the physiological basis for reduced capacity for activities of daily living and work. Thus, it may be a biomarker for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Objective:
To determine statistical properties of cardiac, pulmonary, and metabolic measurements obtained during CPET in people with ME/CFS.
Methods:
Fifty-one females with ME/CFS and 10 sedentary females with similar age and body mass received cardiac, pulmonary, and metabolic measurements during 2 CPETs separated by 24 hours. Two-way analysis of variance and effect size calculations (Cohen’s d) were used to assess the magnitude and statistical significance of differences in measurements between groups. Reliability of CPET measurements was estimated using intraclass correlation coefficients (formula 2,1; ICC2,1). Responsiveness of CPET measurements was assessed using minimum detectable change outside the 95% confidence interval (MDC95) and coefficients of variation (CoV).
Results:
CPET measurements demonstrated moderate to high reliability for individuals with ME/CFS. Comparing subjects with ME/CFS and control subjects yielded moderate to large effect sizes on all CPET measurements. MDC95 for all individuals with ME/CFS generally exceeded control subjects and CoVs for CPET measurements were comparable between groups.
Conclusions:
CPET measurements demonstrate adequate responsiveness and reproducibility for research and clinical applications.
Post-exertional malaise (PEM) is an exacerbation of symptoms that leads to a reduction in functionality. Recognition of PEM is important for the diagnosis and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).
Open-ended questionnaires were provided to subjects following two maximal exercise tests, 24 hours apart. Subjects evaluated how they felt at five time points. Responses were classified into 19 symptom categories.
Results:
ME/CFS subjects (n = 49) reported an average of 14±7 symptoms compared to 4±3 by controls (n = 10). During the seven days afterwards, ME/CFS subjects reported 4±3 symptoms. None were reported by controls. Fatigue, cognitive dysfunction, and sleep problems were reported with the greatest frequency. ME/CFS patients reported more symptom categories at higher frequencies than controls. The largest differences were observed in cognitive dysfunction, decrease in function, and positive feelings.
Conclusions:
A standardized exertional stimulus produced prolonged, diverse symptoms in ME/CFS subjects. This provides clues to the underlying pathophysiology of ME/CFS, leading to improved diagnosis and treatment.
5. Conclusion
The presence of symptoms during and after the two-day CPET and the extended recovery time in the ME/CFS group exemplify PEM. Two key symptoms, cognitive dysfunction and a decrease in function, can potentially indicate the occurrence of PEM. This is consistent with a 2019 survey of 1,534 ME/CFS subjects where the top selected PEM consequence was “reduced stamina and functional ability” (selected by 99.4%) followed by “physical fatigue” (98.9%), “cognitive exhaustion” (97.4%), and “problems thinking” (97.4%). Other complaints prominent in ME/CFS patients after activity are fatigue, muscle/joint pain, headaches and sleep disturbances. The disparity in the time to recover may serve as an additional marker. These symptoms and the rate of recovery contribute to the existing literature on PEM and assist health care professionals in recognizing PEM.
By discerning both the attributes of PEM and its manifestations in each patient, health care providers can identify patients with ME/CFS and devise patient-specific treatment plans to combat the onset and reduce the severity of symptoms. OTs are already familiar with the concepts of energy conservation and activity management but these concepts may need to be modified for ME/CFS patients. For example, more rest may be needed following activity compared to other medical conditions. Patients may reach a plateau of activity which is improved but not close to “normal” since the physiological underpinnings of ME/CFS are not yet fully understood. Early diagnosis and symptom management promote the maintenance of or even improvement in patient function.
This paper also sheds light on the possible risks of a 2-day CPET. It does not appear that patients or research subjects suffer permanent or protracted damage from CPET. Our data show that recovery is bimodal, with approximately half of subjects taking a week or less to recover. This information can be shared with patients or research subjects so that they might make a better informed decision. Exploration of this bimodal pattern may also help discover subgroups within or the pathophysiology underlying ME/CFS.
Chronic Fatigue Syndrome patients should do very short exercise sessions (1-3 minutes), raising their heart rate no more than 30 beats per minute above their normal baseline.
Patients should rest to return heart rate to baseline between these short sessions.
Address oxidative stress, inflammation, and cell function to treat ME/CFS.
“You can’t rest your way out of this illness.”
In This Episode
About Dr. Nancy Klimas … 00:05:08
What is CFS? … 00:06:07
Is CFS a Post-Viral Illness? … 00:07:26
CFS Prevalence … 00:09:51
CFS Predispositions … 00:10:38
How to Exercise With CFS … 00:12:23
CFS Treatment Approach … 00:20:46
CFS Medications and Treatment … 00:24:58
Natural Anti-Virals … 00:28:40
New CFS Research … 00:30:57
Exercise Tips for Chronic Fatigue Syndrome
Physical activity can be very difficult for people with Chronic Fatigue Syndrome. Even a small walk to the bathroom or the mailbox can leave them completely exhausted and bedridden, let alone 30 minutes of exercise.
Dr. Klimas explained that chronic fatigue patients have an extremely low aerobic threshold, and understanding this is key to creating an exercise regime that doesn’t leave them with a chronic fatigue flare up. “They’re much better doing short, but frequent exercise than to try to go longer on endurance.”
Key Exercise Tips:
Do short bouts of exercise with adequate rest in between to allow the heart rate to return to your baseline.
Keep heart rate within 30 beats per minute of your resting heart rate.
Let the patient be the guide.
Keep a log to track progress and understand flares.
She said, “You have to find this gentle way of moving them along and doing little short bits that they can tolerate. And then they’ll become more and more confident when they don’t crash, that they can do a little more…”
[McEvedy CP, Beard AW (1970) Royal Free Epidemic of 1955: A Reconsideration The British Medical Journal 1: No. 5687: 7-11]
Royal Free Hospital former site
re-analysed some of the case notes, and hypothesised that the Royal Free outbreak was epidemic hysteria. This hypothesis was the beginning of an entrenched belief that the disease at the Royal Free, and similar cluster outbreaks, were psychosomatic. This was to have a profound effect on the interpretation of the same illness for nearly 50 years as a presumptive psychosomatic, an interpretation that has lasted nearly 50 years.
[Kermack WO, McKendrick AG. Contribution to the mathematical theory of epidemics. Proc Royal Soc London. 1927;772:701-721]
for the transmission of disease has been used to examine the published admission data from the Royal Free Hospital for the purpose of finding out if the disease had the characteristics of a contagious disease. Similar cluster outbreaks have also been modelled to assess whether they have similar characteristics to the Royal Free outbreak.
Results
Using the 1927 Susceptible Infected Recovered (SIR) model
[Kermack WO, McKendrick AG. Contribution to the mathematical theory of epidemics. Proc Royal Soc London. 1927;772:701-721]
for the transmission of disease, we show that the epidemic of a disease of an unknown aetiology at the Royal Free Hospital in 1955, and other similar twentieth-century outbreaks, have the characteristics of a communicable disease. The disease causing the Royal Free outbreak was given the name ‘Benign Myalgic Encephalomyelitis’ by Acheson
[A new clinical entity? Lancet. 1956;1:789-790]
in 1956, now identified as ME.
Conclusions
By showing that the Royal Free and other ME attributed outbreaks fit the SIR disease model, we demonstrate that the McEvedy and Beard hysteria hypothesis is mathematically incorrect. The ensuing management of the treatment of ME/CFS-like conditions evolving from that, now mathematically improbable belief may need to be re-evaluated.
4. Conclusions
By using the Susceptible Infected Recovered (SIR) model for the transmission of disease
and comparing actual and predicted admission data we show:
The Royal Free cluster outbreak has the mathematical attributes of a contagious
disease.
The cluster outbreaks in Cumbria and Great Ormond Street appear to have the attribute of contagious diseases with similar infection indices (Beta) as the Royal Free.
Furthermore, attempting to model a known hysteria outbreak in Kombolcha yielded no viable solution, and the limited results obtained in no way matched the results from modelling the ME cluster outbreaks.
Thus this work mathematically disproves the McEvedy–Beard hypothesis that the cluster outbreak at the Royal Free was due to mass hysteria.
Leeds Church Institute Arts/Theology Bursary blog post: …but maybe I don’t,
by Dr Charlotte Naylor Davis, 22 July 2020
Charlotte is a biblical scholar who asks a lot of questions and mainly writes about how the Bible has been used and interpreted over history. ‘I have published on heavy metal and the Bible, and feminist critical thinking, and sci fi. I am usually found asking the question “how did we end up thinking the bible said that?”’ She is currently working with a photographer on an art/theology project for the Leeds Church Institute.
My life took a turn ten years ago.
I did an MA in Biblical Studies and towards the end I got ill. No surprise really, as I had worked for churches doing ministry whilst doing a 2 year part time MA in one year full time. When I came to look back on that year with a doctor later we would realise that I didn’t have more that one day off in a row for over six months. But, I was young and had always worked long hours because I have always picked jobs I loved. I was 30. I never got better from that illness.
At first we thought I was merely burnt out. I was diagnosed with depression because I was sad and tired all the time. I spent the year working an admin job so that I could write my PhD proposal in my spare time and my mood lifted. But I was still exhausted. I had pains in my arms and frequent headaches. I had always had awful menstrual issues but now these resulted in me sleeping for often 18 hours straight once the cramps had gone, unable to think or do anything. But most telling that something was wrong was that I started to lose my words. Nouns started to elude me if I was tired. My husband at the time became a master of lateral thinking because I could often only describe the function of something: can you get my bag, its in…that place where we make the food?
Nouns started to elude me if I was tired.
When we moved to Brighton I would go for walks in the downs. I loved walking alone but found myself unable to get up Devil’s Dyke without constant breaks. I had thrown myself into exercise as this was the remedy for depression. Go outside! Fresh air! But the more I did this the worse it got. After a year, two episodes of fainting at the gym and the constant feeling of weakness we were worried something was wrong with my heart and I bullied my doctor into tests. My mood was fine, I was in a loving home doing the PhD I dreamt of, two cats. I was not depressed. I was sick.
It was nice to know someone didn’t think I was making it up. It was frustrating because there is neither a cure nor any real treatment. What is wrong with me is a multi-systemic dysfunction which may be neurological though they don’t give you tests. ME is a debilitating illness which needs more study and I can’t explain it fully here so please do go to the ME Association website and find out more. You see for years it has been treated as a mental illness not a physical one. The problem with this being that you cannot, no matter what CBT you get good at, or positive thoughts you have, think your way out of bed if your legs don’t work. And some days they don’t.
Why am I telling you all this?
Well, my ME has irreparably damaged my life and I’m still not ok with it. I have questions for God about why this happened and how I’m meant to deal with it that are unresolved. And that tension I said I loved so much (see previous blog post)….well, it hurts. It manifests as a grief that I can barely express and I don’t like it.
I realised last year that I have been ill for over 10 years. When I got sick no one talked to me about how this would affect my psyche. They talked about physical issues but no one offered me counselling for what I was losing or would miss out on. A 30 year old who had pushed herself her whole life was now forced by her own body to stop. I was not prepared for what I would lose. The rhetoric of illness I had grown up with was one of ‘fighting’. We treat illness as a battle to be won. So I fought. I refused to give in to this thing. I kept going. I ‘managed’ it by giving over my spare time to rest but carrying on working.
The rhetoric of illness I had grown up with was one of ‘fighting’. We treat illness as a battle to be won.
But if illness is a battle then I lost. I am losing. And I wasn’t prepared for that outcome. I wasn’t prepared for the fact that I would get ill and never get better. And because I was taught to think of it as a battle, then every time I gave in, I failed. So I made myself more and more ill.
Better theologians that me have written about disability. The rhetoric of the battle to be won is incredibly damaging to people with chronic illness. We will not physically win this. Maybe we will mentally win…but honestly when the main symptom of your illness is fatigue, deep, debilitating fatigue, most of the time you haven’t the energy to mentally win at anything.
When I finally accepted that I was ill in a way that was disabling, I had to put down many things I loved. Energy for tasks is a 1:1 swap for me so taking a shower is as tiring as seeing a friend; doing my marking is as tiring a going to the pub. I have to make direct choices before a day starts about where I will put my energy.
I have to make direct choices before a day starts about where I will put my energy.
Going to church became impossible. To get up, dressed, presentable and out of the house in the morning was so tiring, but being in the noise and having to concentrate was even more energy. I was always working on Monday so Sunday had to be a day of rest like I had never done. But that meant a chunk of my ministry – teaching young people – was gone. Part of my identity, the way I expressed my faith and service to God – gone.
People would say I was still useful to God because I could still pray…but let me tell you a secret about your friends with exhaustion and fatigue: sometimes we can’t even do that. You see when I get fatigued I can’t string a sentence together. That noun problem I told you about earlier, it’s got worse. I often say words in the wrong order, I don’t remember names, I barely can articulate my immediate need. So coming from a charismatic background I felt utterly lost in my faith practice. All the things I valued were being taken away.
I have lost so much to this illness. And I battled with it for so long that I didn’t face that grief until last year when I realised my 30s had gone by. People were sharing 10 year photos on facebook and nearly everyone had something good to share, and I suddenly reviewed my 10 years and was faced with 30 year old Charlotte’s abilities vs 40 year old Charlottes disability.
I felt utterly lost in my faith practice. All the things I valued were being taken away.
I’d got a PhD in that time, so you’d think it wouldn’t matter. But the amount I can accomplish in a day is down to about 4 really good hours. (by the way, that makes my ME ‘moderate’, that’s how severe this illness can be). I was faced with all the things I hadn’t achieved, and had put to one side. The stark contrast laid out before me of the friend, sister, lover I had been vs the one that I was now caused me considerable grief.
It still does.
And I am both angry and thankful to God about where I am. I don’t understand my illness. I know it could be worse. But not facing the anger and sadness and only being able to talk about what I’m grateful for has also been damaging. Because I had never felt that I was allowed to hold that tension. I have always felt that I am to be grateful because I’m not as ill as I could be, despite the fact that this illness robs me of my one great gift – language and self-expression – I am always ‘meant’ to be able to turn it around to hope. I hate seeing the tension in people’s faces when I tell them how deeply painful this illness is on physical, spiritual and emotional levels. So I resolve it. I do not love that tension.
But not facing the anger and sadness and only being able to talk about what I’m grateful for has also been damaging.
In my darkest moments I question God because I got ill by following what I believed, and others believed, I was called to do. I undertook those jobs with prayer and discernment – why then did they lead to this?
Now, I know I could have managed my life better. I know that the cause of my ME is not so straightforward. I know that theologies of illness and healing are also not so simple as ‘if I had faith I would be made well’…but my darkest moments I wonder what I did to deserve this. I wonder why I am not healed when my disability has caused me to lay down exactly what I was sure was my calling from God. I question why God would make such frail bodies? What did I do that caused this?
my illness makes me scared and my question comes not from my intellect but from my fear.
You see, questioning is a pastoral issue.
Because I don’t really think that I caused this illness, my illness makes me scared and my question comes not from my intellect but from my fear.
I don’t really want a discussion about healing – I have read and seen enough to know that my body is valuable and wonderful as it is. But my question comes from my grief and my difficulty getting used to this new body and getting used to limitations.
When I ask “what is the point of me if I can’t even pray?” I am not actually asking for an answer, I’m searching for that parental embrace that tells you that your very existence is a joy.
So I have to be honest with you I do not love these questions or these tensions. I wish they did not exist. They pop up when I don’t get a job because of gaps in my CV that are due to the illness, and I get angry. They rear their heads when I forget to call someone and have to make an excuse, or I can’t express a simple request without getting frustrated at my partner and I get sad. They come from wounds which open every time I have to turn down work, or tell a friend I can’t be at something to support them, or tell my family I can’t do Christmas, or my partner that I can’t listen to them today because noise hurts me. They come from a place that some days is too difficult to articulate.
And those questions still hurt, even though I know that God is big enough that I don’t have to choose between frustration and thankfulness. They still just hurt.
I believe God is in the tension even when it hurts. I believe God is in the darkness holding our hand as we get used to new realities. I believe God is the light in that darkness when we feel safe enough to see it again.
As I compile the questions that people have been sending in to Phill (for the House of Questions project) I am mindful of the fact that questioning is a pastoral issue. We want to give something that helps people questions and hold tension and maybe even enjoy it. But I am not taking them lightly. I shall not tell you that you just need to enjoy the tension. I know that some of these things come from your deepest parts and I will be gentle.
because I love questions….but also, maybe I don’t.
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an unexplained chronic, debilitating illness characterized by fatigue, sleep disturbances, cognitive dysfunction, orthostatic intolerance and gastrointestinal problems. Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we analyzed the plasma proteomes of 39 ME/CFS patients and 41 healthy controls.
Logistic regression models, with both linear and quadratic terms of the protein levels as independent variables, revealed a significant association between ME/CFS and the immunoglobulin heavy variable (IGHV) region 3-23/30. Stratifying the ME/CFS group based on self-reported irritable bowel syndrome (sr-IBS) status revealed a significant quadratic effect of immunoglobulin lambda constant region 7 on its association with ME/CFS with sr-IBS whilst IGHV3-23/30 and immunoglobulin kappa variable region 3-11 were significantly associated with ME/CFS without sr-IBS.
In addition, we were able to predict ME/CFS status with a high degree of accuracy (AUC = 0.774-0.838) using a panel of proteins selected by 3 different machine learning algorithms: Lasso, Random Forests, and XGBoost. These algorithms also identified proteomic profiles that predicted the status of ME/CFS patients with sr-IBS (AUC = 0.806-0.846) and ME/CFS without sr-IBS (AUC = 0.754-0.780). Our findings are consistent with a significant association of ME/CFS with immune dysregulation and highlight the potential use of the plasma proteome as a source of biomarkers for disease.
Excerpt from Discussion
Whilst our exploratory study has identified a plasma protein biosignature using machine-learning algorithms that can predict ME/CFS status adequately, the clinical utility of these results remains to be shown. Validation of the panel of proteins in larger cohorts is needed to determine whether it would make a reliable biomarker. In addition, the specificity of the biosignature would need to be assessed to see if it could successfully distinguish ME/CFS cases, as well as ME/CFS cases with or without sr-IBS, from those with other fatiguing illnesses such as fibromyalgia and Gulf War Illness. Disease-specific specific biomarkers could provide an objective measure to aid in diagnosis of this heterogeneous disease. Previous proteomic studies in cerebrospinal fluid and saliva have identified protein signatures with predictive accuracies comparable to ours [11, 14], however, none have led to the development clinical biomarkers. In fact, no molecular biomarkers have been validated for ME/CFS diagnosis or prognosis [4], highlighting the challenges associated with this complex disease. Our work, whilst exploratory in nature, shows that the plasma proteome is a viable and untapped source of potential biomarkers in ME/CFS, and can provide insight into disease pathophysiology. In addition, we support previous results that ME/CFS patients with sr-IBS may constitute a subgroup with a distinct molecular profile [9, 26] and that considering subtypes of ME/CFS can lead to greater predictive accuracy in biomarker studies.
Our study is limited by small sample size, and the robustness of our findings needs to be verified in larger cohorts. Additionally, IBS status determination and stratification could be improved by an independent diagnosis at the time of participant recruitment. Nonetheless, our results comport with other work in ME/CFS that has found evidence in ME/CFS of immune dysregulation, B cell dysfunction, chronic inflammation, oxidative stress, and autoimmunity.
What did the latest study from the Center show? Basically, two things:
There appears to be a distinctive “signature” of a small group of proteins that distinguishes people with ME/CFS from healthy people;
The proteins involved in that “signature” are primarily involved in the immune response—particularly the response of immune cells called B cells—to infections, and the response seen in autoimmune diseases.