What do you think needs to be tested in the blood (plasma, PBMCs, etc) of patients?

I'd love to see the theory that peroxisomes are dysfunctional (Che, Lipkin Bridges 2022) investigated by checking the plasmalogen content of erythrocyte membranes.

We have developed a test method for the simultaneous quantitation of C16:0, C18:0, and C018:1 plasmalogen (PG) species and their corresponding fatty acids (FAs) in dried blood spots (DBS) and erythrocytes (RBC) by using capillary gas chromatography-mass spectrometry.

https://pubmed.ncbi.nlm.nih.gov/37747296/

peroxisomes are the organelle that make plasmalogens and a shortfall of them can lead to stiff erythrocytes that don't deliver oxygen properly.

 

The other finding screaming out for replication is Hwang's WASF3 finding but could you even see it in blood? He used muscle biopsy samples. What you can measure in serum apparently are the Endoplasmic reticulum stress markers GRP78, PERK and CHOP which were also part of his finding (noting that he found a pattern of activation that suggested something had gone wrong with ER stress management).

 

I stumbled across this earlier which looks interesting although it was serum and CSF.

Also there was that muscle on a chip abstract and the two mice studies suggesting something in the blood causes ME like symptoms in healthy animals and tissues. Perhaps that is worth further investigating somehow.

I also agree that WASF3 needs a replication attempt yesterday. I know it's not blood but I really hope the scientific community can get that organised.

 

See this thread
https://www.s4me.info/threads/assessing-current-pem-severity-whether-one-is-in-a-crash.42400/

 

re OP, imho one potential lead is the claim from nanoneedle experiments and other sources that healthy cells in ME plasma become ME like and MEcells in normal plasma become normal.

If this is replicable my suggestion would be to do fractionation experiments to discover the agents responsible.

You could use molecular seives and chromatographic techniques like southern blot for DNA, to create fractions of plasma to distinguish the causal molecule or molecules responsible for this change.

If it is not readily replicable we need to know whether that is a subtype issue or just a bad day at the laboratory kind of issue.

 

I seem to remember Lipkin and Morten metabolomic studies identified important unknown metabolites. I'm wondering if it's possible to replicate the detection of these metabolites/proteins using the tools you have at your disposal. Even if the item detected is unknown, replication in a separate study would provide justification for trying to decode what it is.

 

@Snow Leopard, in case you haven't noticed this thread.

 

I’m hoping that this hasn’t already been done ( maybe by OMF? )

I wonder if using longitudinal/ regular finger prick sampling (through the day and over a few days ) to look at how personal biochemistry changes.

My understanding is that this type of sampling would quench any activity. So use tandem HPLC/MS to investigate differences.

Hopefully then housebound and bedbound patients can also be tested if they choose?

Didn’t they used to check PKU levels on newborn heel prick samples?