Decreased Expression of the CD57 Molecule in T Lymphocytes of Patients with Chronic Fatigue Syndrome, 2019, Espinosa and Urra

Andy

Senior Member (Voting rights)
Abstract

The chronic fatigue syndrome (CFS) is characterized by a prolonged incapacitating fatigue, headaches, sleep disturbances, and decreases in cognition, besides alterations in other physiological functions. At present, no specific biological markers have been described in this pathology. In the present study, we analyzed in lymphocytes the CD57 expression for the diagnosis of CFS, evaluating both the percentage of blood lymphocytes expressing CD57 and the average amount of the molecule expressed per cell.

The study demonstrated a marked and significant decrease in the expression of CD57 in lymphocytes of CFS patients regarding healthy controls. In T lymphocytes, the decrease was significant both in the percentage of cells expressing CD57 (7.5 ± 1.2 vs 13.3 ± 1.6, p = 0.024) and in a more relevant way in the amount of CD57 molecule expressed per cell (331 ± 59 vs 1003 ± 104, p  ≤ 0.0001). In non-T lymphocytes, the decrease was significant only in the amount of CD57 expressed per cell (379 ± 114 vs 691 ± 95, p  = 0.007). The study of CD57 antigen in blood lymphocytes is a useful marker that could cooperate in the diagnosis of CFS patients. Its decrease in T lymphocytes provides most valuable results than the results in other lymphocyte subpopulations.
Paywalled at https://link.springer.com/article/10.1007/s12035-019-1549-7
alt https://sci-hub.se/https://link.springer.com/article/10.1007/s12035-019-1549-7
 
Initial thoughts:
  • N=22, Canadian criteria
  • 9 had Lyme diagnoses but were found to be clear prior to any antibiotic treatment - however no differences in results were found between the 'Lyme' and non-'Lyme' groups in the ME/CFS cohort
  • p-values were nice and low, not clear (on my skim) about Bonnferroni correction but might not be important depending on how many markers they looked at
  • Not sure how valid a biomarker this would be as, despite the clear statistical significance of the results, there appears to be a lot of overlap between controls and patients
  • As often, cannot rule out result could be due to looking at sedentary patients vs non-sedentary controls. Nor if result would also apply to other illnesses.
Interesting study. CD57 seems to come up a lot in various chronic illnesses.
 
CD57 is widely believed to be a marker for Lyme. There are even established thresholds, e.g. under 60 = active Lyme etc. I don't buy into it even though my Infectious Disease doctor does - precisely because supposedly other diseases can influence values. I have a whole multi-colored chart profiling my CD-57 trajectory over the past 15 or so blood draws.

Incidentally, the 9 that had Lyme diagnoses but were found to be clear? I take that with a grain of salt. But I only skimmed this. Will read more carefully in a bit.

Trust me when I say you don't want dueling biomarkers for two controversial diseases; it will only feed naysayers.
 
THE Chronic Fatigue Syndrome (he asked with a shudder)?

One of the ways you differentiate Lyme from ME/CFS is that the latter has PEM. These authors don't seem to recognize that. It is a distinguishing feature for ME/CFS, even more so than swollen knees would be for classic Lyme.

What's chronic Lyme syndrome?

I could go on.

So lets just foist a controversial Lyme marker onto the unsuspecting ME/CFS community. The problem with that is that in the real world of Lyme, many patients with low CD57 numbers test positive for Lyme via conventional CDC 2Tier testing.

Ok, could some of those have ME/CFS too? Could CD57 really be diagnostic for ME/CFS? I guess, but it's purportedly cross-elastic with other diseases too, which always devalued it for Lyme as a diagnostic tool. But the wording used in this seems so....forced, that I am agin it regardless.
 
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CD57 is a protein that sits on those T cells that have the ability to kill other cells (cytotoxicity). In general CD57 sits on CD8 T cells rather than CD4 T cells. CD8 cells tend to recognise bits of foreign protein that has got into cells (e.g. virus proteins). CD4 cells tend to recognise bits of foreign protein floating about outside cells. That links to the killing strategy of CD8 cells - which are there to kill host cells that have got invaded. CD4T cells do not kill usually - they 'help' B cells and other T cells to do other jobs.

There is another protein that sits on the outside of killer lymphocytes, CD56. As a rule natural killer cells, which do not recognise any specific antigens but are more 'innate killers' carry CD56 where the killer T cells carry CD57. Things are not quite that simple but this is the standard situation.

Both CD57 and CD56 carrying killer cells, but chiefly the CD57 T cells, also have the job of killing B or T cells that might be autoimmune or otherwise unwanted. So they have a regulatory function on other immune responses as well as mediating their own responses.

A shift in CD57 expression would be interesting but it is worth noting that a lot of groups have already sifted through lymphocyte subsets in ME and not really found much. For a long time CD56 natural killer cells were thought to be defective but this has not really held up.
 
CD57 is a protein that sits on those T cells that have the ability to kill other cells (cytotoxicity). In general CD57 sits on CD8 T cells rather than CD4 T cells. CD8 cells tend to recognise bits of foreign protein that has got into cells (e.g. virus proteins). CD4 cells tend to recognise bits of foreign protein floating about outside cells. That links to the killing strategy of CD8 cells - which are there to kill host cells that have got invaded. CD4T cells do not kill usually - they 'help' B cells and other T cells to do other jobs.

There is another protein that sits on the outside of killer lymphocytes, CD56. As a rule natural killer cells, which do not recognise any specific antigens but are more 'innate killers' carry CD56 where the killer T cells carry CD57. Things are not quite that simple but this is the standard situation.

Both CD57 and CD56 carrying killer cells, but chiefly the CD57 T cells, also have the job of killing B or T cells that might be autoimmune or otherwise unwanted. So they have a regulatory function on other immune responses as well as mediating their own responses.

A shift in CD57 expression would be interesting but it is worth noting that a lot of groups have already sifted through lymphocyte subsets in ME and not really found much. For a long time CD56 natural killer cells were thought to be defective but this has not really held up.
 
THE Chronic Fatigue Syndrome (he asked with a shudder)?

god i hate this. it reminds me of those dark early days around the Lake Tahoe outbreak when the media used to refer to the illness as this. I think it's maybe an Americanism...?

Yeah, I remember people calling it "The Chronic Fatigue Syndrome" around 1987. I have a feeling it may have been due to the subconscious influence of the 1979 movie "The China Syndrome." The Chernobyl disaster happened in 1986, so the 1979 movie was probably being referenced a lot around that time.
 
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A shift in CD57 expression would be interesting but it is worth noting that a lot of groups have already sifted through lymphocyte subsets in ME and not really found much. For a long time CD56 natural killer cells were thought to be defective but this has not really held up.
Has any body heard anything about CD57 levels rising with some viruses (e.g EBV and HIV) and declining with certain bacteria (e,g, Lyme and mycoplasma pneumoniae)?

I wonder how reliable CD57 is as a marker. Unfortunately, I've seen nothing convincing either proving its utility or disproving it. Some correlation, maybe.

I know it's widely used in Lyme circles. I know too that mainstream dogma states studies show no relation between dwindling CD57 values and Lyme, but I've read those studies - which I think amount to two - and their total combined population studied was 24. 24 out of over 400,000 Lyme cases in the US alone. How can any dogma rest on such flimsy numbers?

Is there an authoritative textbook/source on using CD57 levels as a barometer, or is it all just patchwork speculation and hearsay?
 
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