Cell-Based Blood Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Missailidis et al Feb 2020

https://www.preprints.org/manuscript/202002.0029/v1

 

From the same researchers last year

https://www.s4me.info/threads/an-is...me-cfs-patients-missailidis-et-al-2019.11121/

 

The real test will be specificity with respect to immune and mitochondrial disorders. However, though on the odds this test will fail like all the others, this is what we might see on what will be the eventual successful test. We have to wait for replication and further testing.

 

Wow, if true, this is groundbreaking.

 

A sensible note of caution from @Simon M

https://twitter.com/user/status/1224325448055894016

 

Where are these authors from, and who are they affiliated with?

 

Latrobe University in Australia.

Paul Fisher, one of the authors, presented on their work at the Emerge symposium last year, https://www.s4me.info/threads/video...nsatory-changes-in-me-cfs-patient-cells.9177/

 

It is worth remembering that a test with 100% sensitivity and specificity is useless, because it recognises a group that you have already recognised clinically.

Tests are only useful if they indicate some underlying process that might be recognised better by the test than by clinical assessment. If the test is better it must have a specificity and sensitivity of less than 100% because at least some of the clinical assessments must be wrong (for there to be something better).

 

This line jumps out at me, unfortunately:

This implies patient samples and control samples were not treated equally. If, say, patient samples traveled further before being frozen that might explain a high lymphocyte death rate upon being unfrozen, might it not?

I hope that, upon coming out of pre-print, the peer review process will have necessitated the authors clarifying as to whether patient and HC samples were treated identically.

 

I'm not sure I understand the problem with that. Many diseases are diagnosed this way. It's not ideal but nothing ever is.

 

One of my concerns is that ME might turn out to be some kind of spectrum disorder, and that we share hundreds of potential biomarkers but no biomarker is core to the disease.

 

I thought it interesting that they made reference specifically to co-morbid POTS in the CCC-guided patient selection.

Would seem to me like including those with POTS makes drawing any conclusions harder, given the many known diseases and issues that present with POTS beyond just CFS/ME. I doubt they were experts in POTS too and able to confidently exclude all of these.

Even if they did, POTS research is showing secondary mito dysfunction in many of the patients, not all of which have a CFS/ME diagnosis...

 

I really think they are on to something. Their main idea is that Complex V inefficiency is the root cause of ME/CFS. I don't understand exactly what Complex V is and what it does, however it seems that ME/CFS might be a milder form of a genetic mitochondrial disease called Complex V deficiency.

The bold part describes ME/CFS very well, or at least a subset. Namely, extreme lactic acid build up and muscle fatiguability after trivial / minor activities, such as walking, staying upright, etc. I recall reading several papers confirming this lactic acid issue.

I wonder though if Complex V deficiency also has PEM as a symptom?

PS:

Another mitochondrial disease affecting the complexes, Leigh's disease seems to be triggered in certain cases by a sudden stressor. From wikipedia:

If this mitochondrial disease can be triggered in such a way, then maybe ME/CFS could be triggered in a similar manner? Very interesting.

 

The world of POTS is messy as well. Some of the internationally known POTS specialists do not believe in ME and believe those who have ME have primary POTS. Then their POTs patients are ‘tired’ too. Many if not all display several symptoms which overlaps with ME, without ever being diagnosed with ME.

Other than Dr Rowe, POTS and ME specialists are not typically mingling and in my view, they should. They should be invited to ME conference and vice versa.

To add to the complexity of just being diagnosed, first line physicians are not necessarily able to identify patients with POTs that come to their office. In my case, when i initially went in because i was feeling worse upright and slightly better reclining, i was deemed lazy and depressed and told i needed anti-depressants. I had to go 7 hours in a plane to a doctor who knew exactly what was wrong. And when i got back the doctor was still in disbelief, though willing to prescribe me atenolol which had been started in the US. It was another 8 years until she was willing to do a NASA lean test so I could be included in a study.

 

This is just plain wrong. Your perfectly identified clinical diagnosis of me/cfs still makes you a psychiatric patient in 99% of all cases.