Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS),2021,Fluge,Mella,Tronstad

Thank you. I'm very curious about his views of ME as non-classical autoimmune disease.

 

Thank you so much @Kalliope

 

My pleasure. The translation was done very quickly during watching the lecture for the first time and with brain fog. I tend to loose a lot of vocabulary then, but hope at least main messages came through.

He says he can't find any of the typical tissue damage in ME patients which you would have expected in typical autoimmune diseases. No histologic inflammation. With pathogenic antibodies as in lupus, rheumatism, you will see tissue damage. He has not (yet) seen this in ME patients.

He went on to list everything they have done to look for specific autoantibodies in ME/CFS over ten years with no result.

ETA: Which was a quite impressive list on a slide at 31 minutes and includes a picture of him and his wife collecting pig tissue (dorsal root ganglion) at a slaughterhouse

 

Thanks so much @Kalliope for sharing this and for the extensive summary. Indeed pretty advanced and hard to follow but easier with Fluge's slides and your notes. I always appreciate the chance to listen to some Norwegian as well, it's like Danish but nice

 

Glad you could follow the lecture in Norwegian as well. I feel their paper from last spring on their hypothesis on disease mechanisms for ME drowned in the pandemic and never received the attention it deserved. Otherwise I'd think some journalists would have gotten interested and we might have had some media articles helping with breaking it a bit down for us. Hopefully it's not too late.

ETA: Danish is much more charming to listen to than Norwegian, by far!

 

The study referred to:
https://www.s4me.info/threads/prepr...patients-with-covid-19-wang-et-al-2021.19230/

That's the first time I've ever seen anyone call Danish charming Sorry folks, Scandi in-joke (and as a half Dane I'm allowed to joke about it).

ETA: very interesting talk, and good summary @Kalliope

 

Indeed, pandemic news would have diverted some press attention from studies like this, for better or worse. I suppose to the degree Fluge et al's model might actually hold together as future clinical studies and research (by either themselves or others) seek to test its different components, the paper would gain renewed relevance and we'd hopefully see more accessible versions of the model itself. I liked how Fluge emphasised at the beginning that this is their best bet at a theory as of now, e.g. there is always room for error and refinements as things develop. Will be exciting to follow...

And a rare fan of Danish, lovely to see!

 

I guess if you read between the lines is he saying that cognitive techniques have no way of doing anything for ongoing/active immune activation and vascular dysregulation - so where these are generating the symptoms no difference would occur? But yes what is he including in 'secondary autonomic adaptations'? And what is he including in coping strategies?

- it could be as far as saying those who are mild and can do some things will get benefit from proper pacing/reduced exertion/better support and understanding around that as they can actually stay beneath their baseline and adjust to their disability, but I wouldn't call those 'cognitive', 'psychosocial'. I wonder whether it is 'this bit is off my turf, but this other bit it definitely doesn't work for'?

 

I think that last line of yours is important. Just as they develop synacthen test type things to differentiate secondary from primary in those various illnesses, are there any mechanisms that could be probed to separate these out? I guess just like with those conditions it could be that there are different causes/issues for different individuals/types causing 'similar' outcomes? But maybe I'm showing my lack of knowledge?

 

So Chris Ponting checked the UK Biobank to see if the claim of an HLA association, in ME/CFS ("*" & "**"), applied to that (UK Biobank) cohort and it didn't - correct?

Seem to recall that the Norwegian group found an association with TPPP gene*** which also wasn't replicated in the UK Biobank (correct?). Still if we can identify a genetic signal for some people then that would be useful.
Wonder if selection criteria for Norwegian biobank would explain the difference and/or the genetic characteristics of the Norwegian group?

*"Association to specific HLA genes"
9.48 minutes from start
**https://www.nature.com/articles/s41598-020-62157-x
*** https://www.s4me.info/threads/genet...022-hajdarevic-et-al.25070/page-2#post-411286

 

The focus on the immune system may be based on the HLA association and that association wasn't replicated in the UK Biobank cohort --- so the whole immune/autoantibody thing may not hold up if the HLA association is incorrect.

*https://www.nature.com/articles/s41598-020-62157-x

 

Øystein Fluge held a presentation at RME last week (in English) where he goes through the findings in this paper:
YouTube: Pathomechanisms in ME/CFS - a model

Fluge and Haukeland University Hospital in Norway are now recruiting up to six patients to a pilot study where they will target plasma cells using the anti-cd38 monoclonal antibody medication Daratumumab. Study start date was 1 June 2022 and is set to end on 1 June 2024.