Multi-omics identifies lipid accumulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cell lines: a case-control study, 2026, Missailidis et

Thanks @chillier and @DMissa, very helpful.

The paper reported a lot of good detail about the machines and the techniques in Methods. I think it would also be good to report when analyses are subcontracted out, giving the name of the lab that did the work. For the reasons we have discussed, it does matter who does the work, probably at least as much as which machine was used.

Readers would see the name of the lab and some would immediately have a good idea of the protocols likely to have been applied and the quality of the work.
 
Hutan said:
I think it would also be good to report when analyses are subcontracted out, giving the name of the lab that did the work. For the reasons we have discussed, it does matter who does the work, probably at least as much as which machine was used.
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They are co-authors with their contributions and affiliations listed in the paper:


Daniel Missailidis 1,2,✉, Christopher W Armstrong 3, Dovile Anderson 4, Claire Y Allan 1,2, Oana Sanislav 1,2, Paige K Smith 5, Tammy Esmaili 6, Darren J Creek 4, Sarah J Annesley 1,2,7,#, Paul R Fisher 1,#
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1Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, VIC Australia
2La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC Australia
3Department of Biochemistry and Pharmacology, The University of Melbourne, Melbourne, VIC Australia
4Monash Proteomics and Metabolomics Platform, Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC Australia
5Monash Health, Melbourne, VIC Australia
6Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, VIC Australia
7La Trobe Institute for Sustainable Agriculture and Food, La Trobe University, Bundoora, VIC Australia


D.M and C.W.A wrote the original draft. D.M, C.W.A and D.A analysed the data. D.M, C.Y.A and O.S cultured and harvested the cell samples. D.A prepared the samples for MS and ran the MS in the laboratory of D.C. P.K.S, T.E, D.M and S.A undertook home visits to collect samples from people with ME/CFS. S.A and P.R.F acquired the funding, conceived the study, advised experimental design and analysis and supervised junior researchers. All authors read and approved the final manuscript.
 
So if I have understood this correctly, these B cells are in a state of increased rigidity of cell membranes, which alters how they receive and send signals?

And we aren't sure if this is a side effect of an underlying metabolic issue or if it is "intended" because the cells are doing so in response to some signal? A bit like some kind of chronic activation?

And it might be part of the disease loop. Can B cells end up in this state after an infection?
 
Hoopoe said:
So if I have understood this correctly, these B cells are in a state of increased rigidity of cell membranes, which alters how they receive and send signals?
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It is a possible consequence of some of the observations we made. We still have to verify those observations in primary cells and directly test whether accompanying changes that we think may occur do actually occur.
Hoopoe said:
And we aren't sure if this is a side effect of an underlying metabolic issue or if it is "intended" because the cells are doing so in response to some signal? A bit like some kind of chronic activation?
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If what we've seen does happen in cells in the body, yes, we don't know why it would be happening and it may be due to an intrinsic metabolic reason or a broader signalling reason. The thing with these sorts of immune cells (in this case B cells) is that they can completely remodel their metabolism at different stages (of eg: maturation) or as part of response to signals. So when we see shifts "on average" it could reflect cells in different stages, or responding to different signals, or responding to the same signals differently, or a combination. It could reflect an intrinsic metabolic issue that does affect B cells, but I'm guessing that the chances of this are probably lower due to how easily small shifts in any of the many complex immunological events can lead to drastic "on/off" degrees of metabolic pathway changes. ie those explanations are probably more likely in terms of raw chance? We have some work coming up that may help clarify this tho. This is all just my supposition.

Hoopoe said:
And it might be part of the disease loop. Can B cells end up in this state after an infection?
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It depends on what "this state" really means here. We can guess around but I would not comment until we do validation on primary cells straight from the body. The cell lines are useful to quickly and cost effectively screen for things being overtly different (or due to stable factors such as genetics which will survive the transformation process) but in terms of pinning down shifts in things as parts of a potential disease process we need to use cells that have had less done to them and with better characterised cohorts. That is what I am trying to push my newer research towards.
 
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SMPDL3B seems like it might be related to this lipid accumulation (at least in a very superficial way, without checking the details)

SMPDL3B is a membrane-associated protein involved in membrane lipid catabolic processes and sphingolipid metabolism. It acts as a negative regulator of inflammatory responses and Toll-like receptor (TLR) signaling.
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It is found in extracellular exosomes and is associated with lipid rafts on cell membranes.
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Just checked some other databases to see if Daniel's surprising lipid, the one that separated cases and controls, was measured in other studies. It does seem to have been, assuming PC 0-38:4 always refers to the same thing. Anyway the other studies I found have it similar in cases and controls, so Daniel's result could be an example of random variation clustering.

If it is not mere chance though, it could be interesting as it seems to be a plasmalogen, which is a topic of interest to me/cfs. (Che, Brydges, Likpkin et al 2022).

There's a group at Monash University here in Melbourne that are studying plasmalogen replacement therapy with some success. (Paul, Meikle, 2021). I took a supplement rich in alkylgylcerols for a while (a digestive-stable plasmalogen precursor) and it certainly didn't kill or cure me (although the experiment was confounded by a lot of factors, as is the case with n=1, especially when you expect the thing would work only after a time lag).
 
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Murph said:
assuming PC 0-38:4 always refers to the same thing
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It may not

also may not be a plasmalogen, depends on a chemical property that we couldn't discern from this type of data

The baker institute lipid people are involved in that work you have referenced going by Meikle's name being there. If I got funding for a bigger project on this there's a decent chance some of the baker people might be involved as they are the local experts on lipid profiles in immune cells and have a very nice facility for looking at this stuff. I haven't had conversations with anybody yet but I hope to once I have some time to get my ideas straight for a coherent project with disease plausibility. At the moment far too snowed in with 5 other 3+ year major projects to give this one the follow up time I'd like to. Sitting quietly and ruminating is a luxury I can scarcely afford at the moment. Lots of live samples coming in and things like that. Plus some time sensitive major experiments with a few hundred samples. It'll calm in some time but not for a while.

May be a good thing as I will have more data and information to judge what the best use of my future time and resources would be. There could be more compelling angles that come out of some of this work than what has been reported here
 
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