Could bone marrow studies be useful?

Posts moved from Deep Sequencing of BCR Heavy Chain Repertoires in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, 2025, Ryback et al

Bone marrow studies might be a good future target, there is one person I know of with bone marrow samples from ME/CFS patients but I'm unsure of what condition they are in.

 

I don't think so, I'll ask some questions about their availability and quality.

It would be nice to try clear up if the cell themselves are developing abnormally or if they're responding normally in the context of their environment. Though I'm not sure a bone marrow study would entirely answer the question.

 

A big problem with bone marrow is heterogeneity within the tissue. Different types of cells are competing for niches to develop in. We have no successful studies of marrow in other diseases like lupus or RA that answer this sort of question as far as I know.

Bone marrow sampling is also very painful in many cases.

 

I think we know what the question is and I think @MelbME would agree. It is whether any skewing to VH3-30 is occurring because of a shift in checkpoint-dependent selection in the bone marrow environment or once the cells have gone out into lymph nodes. If we could answer that it would be of huge value.

But it needs very careful usage of controls and normalisations of data. If bone marrow sampling was easy it would be a viable project - maybe a pilot study of 50 pro bands and 50 controls and then scale up and replicate with 200 of each. But that would be very tough.

It is not so much looking for a needle in a haystack as trying to establish whether heartsease is a commoner weed in Martlesham fields than Boromeswell fields using 20 samples of ground ten metres in diameter at each site when heartsease grows in scattered clumps depending on the amount of moisture, sunshine, slope, recent fertiliser dressing and what crops were grown last year. You might need 1000 samples, not because heartsease is hard to find but because it is patchy.

I suspect that to get a reliable estimate of a B cell repertoire shift you might need ten bone marrow samples from the same patient.

 

Does that mean 50 PwME and 50 control people? (I'm not sure if you're talking about people here or some bit of people's biology).

What disease would a PwME have to have to have ten bone marrow samples as part of the investigation/treatment? Is there such a thing? If so, can we glom onto the relevant clinics and do the research?

 

yes

The problem is that one bone marrow sample is very unpleasant. People with life-threatening leukaemia may get half a dozen bone marrows over a period of months or years but one at a time. To do this B cell sampling in ME/CFS you would need ten samples on the same day. A bit like being in the first row at Agincourt I suspect.

And of course it would be of no value to that person's treatment. There is no way I could ask a patient to undergo that.

 

Could bone-marrow sampling be done as part of organ donation when a PwME has passed away? The MEA has an information leaflet about organ donation, though it says that only about 1 in 100 people die in circumstances that would allow organ donation.

Or could a single bone marrow sample taken from a PwME because of leukemia be grown in a lab to yield more samples? (Not sure if that addresses the patchiness problem.)

 

If they were killed in a traffic accident maybe but the cost of organising that would be astronomical - many millions.

No because B cells only grow in bottles if you bock normal selection controls - so the population of antibodies produced would be entirely an artefact of the culture system.

 

I'm going to have one last go. This says that that bone marrow is usually taken from the hip. What about PwME going under anaesthetic for hip surgery, such as hip replacement? Or indeed general anaesthetic for anything? Or would the pain or infection risk after taking samples be significant?

 

Something like that.

 

Yeah this was my fear and I hadn't even thought 10 samples, that's just not something worth doing now. If the VH3-30 was to become accepted as a clear part of the disease mechanism then maybe someone does the bone marrow study but this is a project on the scale of DECODE in terms of cost and time.

Nevertheless, I'll still check to see what number of samples are available if any.

 

Hip replacement idea is clever, I wonder if that would be possible.

 

I think DecodeME only cost £3.2m, which is peanuts in the grand scheme of things. The UK government blew £5m on PACE, which was utterly without merit. RECOVER spend $US 1bn without finding anything. If this is an important study, I think the money should be spent, if a strong case can be made.

 

It is, but I wonder how many are done?

Several friends and close relatives of my age (mid-60s) have already had hip and knee replacements. Mine are in fantastic nick, though! Not because I've been lucky or careful; because for the last 25 years I've been unable to do most of the things that wear them out.

 

From Wikipedia:

 

Sorry, I wasn't very clear, was I! What I meant was, how many are joint replacements are done in people with ME/CFS?

The frequency could be significantly lower than average, since many of us can't do nearly as much activity as healthy people. Some of us probably have unusually low levels of wear and tear damage.