Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes 2022, Schutzer et al

Steven E Schutzer, Tao Liu, Chia-Feng Tsai, Vladislav A Petyuk, Athena Schepmoes, Yi-Ting Wang, Karl Weitz, Jonas Bergquist, Richard Smith, Benjamin Natelson

preprint

Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia. We quantified a total of 2,083 proteins using immunoaffinity depletion, tandem mass tag isobaric labeling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1,789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p-value < 0.05. This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.

https://www.biorxiv.org/content/10.1101/2022.09.14.506792v2

Edit: Now published, see post #12

 

You'd think they might have wondered whether the proteome profile is also the same in healthy people, wouldn't you. Because that would tell them something different altogether.

 

Interesting that Canadian Blood Services disallows blood donations from people with "Chronic Fatigue Syndrome", as it's labeled by CBS, but allows donations from people with Fibromyaligia.

Who is right? Are these two separate diseases, or are they one and the same, just varied manifestations?

 

They are different clinical problems.
The study above contributes nothing to the discussion on whether they may have some common causes or mechanisms isms. You might as well study CSF in people with thyroid disease and hypertension and say because the results are the same the diseases are the same. Barmy.

 

Where is the fibro only control? Others already mentioned healthy controls.

 

Thank you @Jonathan Edwards, I appreciate your assessment of the article.

Yes, now they are viewed as separate diseases, but several years ago, some in medicine called them "cousin illesses", or cousin syndromes as they were seen at that time.

Interesting that in some closely related family members there have been cases of some members being diagnosed with ME, while others have been told they have FM.

Perhaps that's where the "cousin illness/syndrome" idea came from.

 

Really illustrates (to me) that we need something like GWAS to identify the underlying disease pathology. This study hasn't turned up anything to identify disease pathology of either ME/CFS or FM ---
I'm hoping that GWAS will provide clues to potentially disrupted pathways and then technology like this [mass spectrometry-based proteomics] can be applied to identify biomarkers, drug targets ---

 

Assumption here being that CSF carries the underlying signature of both diseases.

 

This tells us no such thing. They looked at 1,789 shared proteins and, quite rightly, corrected for the huge number of comparisons. That makes it very hard to find statistically significant differences and with n=15 they could only hope to find enormous differences. Not statistically significantly different does NOT mean 'the same'.

 

Published as Myalgic encephalomyelitis/chronic fatigue syndrome and fibromyalgia are indistinguishable by their cerebrospinal fluid proteomes (2023, Annals of Medicine)

 

Indeed and then there is the issue of overlap/comorbidities and diagnostic certainty making it hard to be sure quite what they are looking at other than ‘people diagnosed with x or y’ (but you can’t be sure they don’t also have x,y,z or anything else I assume)?

 

Merged thread

Abstract
Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other.

Material and methods
To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n = 15) and one without (n = 15) fibromyalgia.

Results
We quantified a total of 2083 proteins using immunoaffinity depletion, tandem mass tag isobaric labelling and offline two-dimensional liquid chromatography coupled to tandem mass spectrometry, including 1789 that were quantified in all the CSF samples. ANOVA analysis did not yield any proteins with an adjusted p value <.05.

Conclusion
This supports the notion that ME/CFS and fibromyalgia as currently defined are not distinct entities.

1. 
   Key message
2. ME/CFS and fibromyalgia as currently defined are not distinct entities.
   
   
3. Unbiased quantitative mass spectrometry-based proteomics can be used to discover cerebrospinal fluid proteins that are biomarkers for a condition such as we are studying.
   
   
   
   https://www.tandfonline.com/doi/full/10.1080/07853890.2023.2208372

 

This is interesting.
I started off with a diagnosis of severe ME over 20 years ago. At year 12 my pain levels went through the roof and my doctor at that time decided I had fibromyalgia as well. One of my old friends from university had exactly the same illness pattern. It is hard to tell where one illness starts and the other begins.

My aunt had a diagnosis of fibromyalgia only, but we often used to compare notes and our symptoms were very similar except I was at the more severe end of the spectrum. Bizarrely I found doctors to be more sympathetic of my fibromyalgia diagnosis, despite the fact the ME type symptoms were far more disabling.

 

Clinical specimens for this study

A total of 15 and 15 subjects were included in the CFS-only and CFS + FM groups, respectively. They were diagnosed as reported [Citation7]. Thus all subjects fulfilled the 1994 case criteria for CFS [Citation8] as modified by BHN to include severity: Patients had to report at least a substantial reduction in activity across a number of life spheres where substantial was ‘3’ of a 0 to five Likert scale (0 none; 1 mild; 2 moderate; 3 substantial; 4 severe and 5 very severe). The same Likert scale was used to assess symptom severity. So, in the month prior to intake, subjects had to report at least a substantial problem with three of the following symptoms plus at least a moderate problem on a fourth of the following list: sore throat, tender lymph nodes; headache; myalgia; arthralgia; unrefreshing sleep; problems with attention and/or concentration; and the complaint that minimal effort – physical or emotional – produces a dramatic worsening of symptoms – known as post-exertional malaise. All subjects tested negative on a set of rule out bloods used to identify medical causes of fatigue including anaemia, liver dysfunction, thyroid problems or possible autoimmune diseases. Subjects were also evaluated to determine if they fulfilled criteria for the 1990 case definition for fibromyalgia. Thus subjects given the co-morbid diagnosis of fibromyalgia had to report four quadrant pain and have at least 11 of 18 tender points on palpitation using 4 kg of force at each point [Citation9].

 

Abstract
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia have overlapping neurologic symptoms particularly disabling fatigue. This has given rise to the question whether they are distinct central nervous system (CNS) entities or is one an extension of the other. To investigate this, we used unbiased quantitative mass spectrometry-based proteomics to examine the most proximal fluid to the brain, cerebrospinal fluid (CSF). This was to ascertain if the proteome profile of one was the same or different from the other. We examined two separate groups of ME/CFS, one with (n=15) and one without (n=15) fibromyalgia.

But shouldn't they have had a separate fibromyalgia only group if they were looking for differences?

ETA: Apologies didn't read the previous posts from the merged thread.