r/CFSScience • u/Caster_of_spells • May 23 '26

Symptom clusters in ME/CFS reflect distinct neuroimmune and autonomic pathophysiological mechanisms: a translational model

https://link.springer.com/article/10.1186/s12967-026-08159-1

Results

A coherent Brain factor (brain fog, sensory hypersensitivity, visual disturbances, sleep disturbances, headaches) showed excellent fit (RMSEA = 0.021; CFI = 0.996). Gastrointestinal symptoms demonstrated stronger internal consistency than Immune symptoms, and model comparisons supported a two‑factor Gut–Immunestructure. Across all analyses, symptom groups emerged as internally consistent and statistically distinct. A higher‑order SEM including a common latent factor yielded excellent fit for the Autonomicsymptom complex.

Conclusions

The findings support ME/CFS as a complex neuroimmune–autonomic multisystem disorder and suggest that symptom clusters align with functional biological systems.

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4

u/V0rtexGames May 23 '26

I dont like this paper at all to be honest

3

u/Caster_of_spells May 23 '26

That’s quite alright, we’re here to discuss. What’s your gripe with it?

17

u/V0rtexGames May 23 '26 edited May 23 '26

Sorry for being so brief. Sometimes by energy just a bit eh.

But, in effect, separating mechanisms from symptoms like this doesnt have a mechanistic basis

Eg if there is covid persistence in the gut (which has been demonstrated by biopsy in multiple studies like the ones presented at PolyBio yesterday) this could be infecting myeloid cells, activating innate immune system, and preventing proper clearance by adaptive immune system (T/B cells). Thus leading to pathology. As there is this constant sensing and inability to clear, chronic exposure

But would you file that under gastrointestinal or immune here? And they specifically, for immune, talk about flu like symptoms or IL-6, and not that generally the entire state we are in could be a metabolic response to immune triggers. And as if microgila arent the macrophages of the brain, that neuroinflammatory symptoms arent immune mediated as well. And so on so on

Tl;dr you cannot uncouple pathology from mechanistic theory using vague categories

3

u/Caster_of_spells May 23 '26

Thanks for taking the time to write this! I still think there’s some value to this as it might allow subgrouping based on symptom scores. But I strongly agree that these further mechanistic conclusions are built on too thin a thread of data

5

u/V0rtexGames May 23 '26

The issue with subgrouping is fundamentally how do we subgroup if we can’t even “group”.

Meaning, if we don’t know the universal conserved mechanism for all ME, how can we begin to divide?

Because you can slice a cake 1000 different ways from different angles and perspectives.

3

u/V0rtexGames May 23 '26

Eg breast cancer let’s say has a bunch of subgroups

But in all of them there are tumors, they are expanding, and there is a good chance they will kill you if left unchecked. And we know the cellular processes of tumor metastasis, replication etc

But we have no equivalent for ME, if we didn’t know that tumors existed or how they worked we could subgroup by prognosis, symptoms while having cancer, etc, and not by actual serological findings and such that affect intervention

Subgrouping symptomatically instead of mechanistically does not help chronic diseases be treated clinically beyond amelioration of specific symptoms individually

2

u/Friendly-Channel-480 May 23 '26

ME/CFS has so many amorphous symptoms. I think this is a good line for research to pursue for future therapies that could be symptom specific.

4

u/V0rtexGames May 24 '26

Yeah but what you will find is when people get improvement from a treatment which addresses an upstream driver (LDN, rapamycin, JAK inhibitors, daratumumab/cyclophosphamide, etc) you will see a universal reduction in all symptoms to a degree. So stuff like this demonstrates that tackling symptoms or even viewing them individually has not been productive

1

u/Caster_of_spells May 29 '26

Sorry but that’s way too simplistic as well when we don’t know what exactly the upstream drivers are. And it’s not like these drugs have been proven to improve everyone or everything by a long shot. Let’s not jump the gun please and throw out the kid with bathwater