SequenceME genetic study - from Oxford Nanopore Technologies, the University of Edinburgh and Action for ME

[Utsikt]

If the genetic analyses showed differences between ME/CFS triggered by COVID and ME/CFS not triggered by COVID, wouldn't that raise the question of further subtyping or different diseases based on triggers?

If they are wastly different - probably yes.

If there are some minor differences, they might just be due to the covid-ME/CFS being confounded by signals related to the susceptibility to covid infections.

If we had enough samples, the WGS from EBV-ME/CFS might also look different than the WGS for ME/CFS in general.

So minor differences would be interesting, but might not mean there are subtypes of ME/CFS itself.

 

[Jonathan Edwards]

If the genetic analyses showed differences between ME/CFS triggered by COVID and ME/CFS not triggered by COVID, wouldn't that raise the question of further subtyping or different diseases based on triggers?

Long Covid genetics might throw up genes that reflect Covid viral protein recognition leading to a different level of immune response but the same ME/CFS in the end. For instance there might be an HLA allele or haplotype link.

 

[rvallee]

But it sounds as though the team really need support from other donors now to keep the project moving forward quickly. The next step in Phase 2 is analysing the data, it will cost about half a million pounds and take about a year.

A significant fraction of this can probably come from donations, with the right social media campaign. Every step along the way makes further steps more likely to be funded.

Although obviously even better would be the German funding going in part to this, it's such a no-brainer.

 

[Robert 1973]

Although obviously even better would be the German funding going in part to this, it's such a no-brainer.

If the MEA still has excess money in the bank, the £500k–£1m needed to fund the analysis would seem to be an ideal project to spent it on.

 

[MeSci]

Mark Smith
BBC Radio Gloucestershire

People suffering from Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome, say new government funding for research into the illness is "a drop in the ocean" compared with how much is really needed.

Helen Stout, 67, from Cam in Gloucestershire, says she has not been able to "ride a bike, cook a meal or jump in puddles with the grandchildren" since becoming unwell in 2020.

"ME causes this country a huge disease burden. This funding is a drop in the ocean," she said.

The government is spending £4.75 million on the research, saying it will be the world's largest study of its kind, offering new hope to around 390,000 people living with the condition in the UK...

Rosie Barrett, 32, from Budleigh Salterton, Devon, has had to become a full time carer for her sister, Alice, 29, whose been bed-bound due to ME for five years.

"Even when you look at how much the government has invested recently, it's nothing compared to other illnesses," she said.

'ME left me unable to ride a bike, cook or play with my grandkids'

People with ME say new government funding for research into the illness is "a drop in the ocean".

www.bbc.co.uk

 

[hotblack]

Long Covid genetics might throw up genes that reflect Covid viral protein recognition leading to a different level of immune response but the same ME/CFS in the end. For instance there might be an HLA allele or haplotype link.

That’s interesting. So maybe one reason there was none with ME/CFS is precisely because it can be triggered by so many different things? Disparate triggers converging on something downstream? Whereas with LC there is one common trigger?

 

[Jonathan Edwards]

triggered by so many different things? Disparate triggers converging on something downstream? Whereas with LC there is one common trigger?

That's the idea.

 

[Robert 1973]

That’s interesting. So maybe one reason there was none with ME/CFS is precisely because it can be triggered by so many different things? Disparate triggers converging on something downstream? Whereas with LC there is one common trigger?

I can’t remember, did the DecodeME questionnaire include any questions about whether participants’ ME/CFS followed any specific identified infections (eg EBV/glandular fever)?

If there is data on participants whose ME/CFS followed EBV, then presumably we might have expected to find variants in genes which affect the immune response to EBV, just as we might expect to find variants which affect the immune response to Covid in people with LC?

 

[Andy]

I can’t remember, did the DecodeME questionnaire include any questions about whether participants’ ME/CFS followed any specific identified infections (eg EBV/glandular fever)?

Question 25 in the screening questionnaire.

Did you have an infection when, or just before, your first ME/CFS symptoms started?
□ Yes, glandular fever
□ Yes, COVID-19
□ Yes, another infection
□ No (Skip to Question 27)
□ Don’t know (Skip to Question 27)

 

[Jonathan Edwards]

If there is data on participants whose ME/CFS followed EBV, then presumably we might have expected to find variants in genes which affect the immune response to EBV, just as we might expect to find variants which affect the immune response to Covid in people with LC?

The Edinburgh team have data indicating that a substantial minority of people with ME/CFS identify EBV as trigger. It is quite interesting, in that light, that DecodeME did not find a DR linkage. (DR controls most of the presentation of microbial antigens to T helper cells.) Even DQ looks to have given no major signal.

That might suggest that nothing is likely to come up for Long Covid either, but the risk weightings might be rather different, especially if quite a lot of Long Covid turns out to be self-limiting over no more than a couple of years. As far as I know, what genetic data we have for LC so far has not picked out any HLA risk alleles.

I think the lack of HLA-D linkage is quite good evidence against any theory based on the idea of foreign antigen triggering autoimmunity. There really ought to be a DR link if that was what happened I think.

 

[Binkie4]

Question 25 in the screening questionnaire.

Did you have an infection when, or just before, your first ME/CFS symptoms started?
□ Yes, glandular fever
□ Yes, COVID-19
□ Yes, another infection
□ No (Skip to Question 27)
□ Don’t know (Skip to Question 27)

@Jonathan Edwards
The question asks " Did you have an infection when, or just before,your first ME/CFS symptoms started"
I wasn't totally sure how to answer this question and it's possible that, because of the nature of ME, it might have been difficult for others too.

It depends on how I look at the timings of my illness. I have believed since learning of the nature of ME that glandular fever was at the root of it but I had that in March 1986 and I was not diagnosed with ME until 2008. I think I ticked the box for glandular fever on the basis of a solid diagnosis based on repeated blood tests and a spinal tap. I was told I had a glandular fever like virus. I had a diagnosis of post viral fatigue syndrome for some months after it and couldn't work then. I continued to have low stamina and never worked full time again.

I was eventually able to work part time building up to 4 days a week and then down as I became more ill again until I retired 12/13 years later. I didn't connect my energy loss with ME until about 8 years later when I was completely bed bound for a while, and an endocrinologist I saw for another condition listened fully and diagnosed me with ME, confirmed at Dr Bansal's Chronic Fatigue Service clinic.

I now think I had mild ME since 1986 not low stamina as I had explained it to myself.

 

[Amw66]

Glandular fever is also triggered by CMV .
We don't do serology much here to be able to distinguish which one is the culprit .

It's a glandular fever positive / negative test in Scotland , unless something has changed post COVID .

 

[Jonathan Edwards]

It's a glandular fever positive / negative test in Scotland , unless something has changed post COVID .

I am not sure that is quite right. One screening test is for the presence of atypical large lymphocytes, which may not be completely specific but is characteristic of EBV and not designated a 'glandular fever test'. After that there are tests for rising EBV antibodies and likely PCR. Not since I was a teenager have virologists talked of 'glandular fever' as far as I know. Cytomegalovirus may produce 'mononucleosis' (the large lymphocytes) but my understanding is that it is an u common cause of clinical or pathological confusion.

 

[Binkie4]

I was told after my first blood test that I had 'reactive lymphocytes ++'. There was no Dr Google then so that is how it stayed apart from the addition of ' a glandular fever type virus'.
I was teaching in a 6th form College on teaching practice and the other postgrad teaching student became ill on the same day as well as our senior lecturer tutor.

 

[tornandfrayed]

I am not sure that is quite right. One screening test is for the presence of atypical large lymphocytes, which may not be completely specific but is characteristic of EBV and not designated a 'glandular fever test'. After that there are tests for rising EBV antibodies and likely PCR. Not since I was a teenager have virologists talked of 'glandular fever' as far as I know. Cytomegalovirus may produce 'mononucleosis' (the large lymphocytes) but my understanding is that it is an u common cause of clinical or pathological confusion.

I wish I'd asked questions when I was younger. I assumed that I had reasonable evidence that it was EBV that triggered my ME because I had a negative test during another infection a couple of months before. Then later after I had been ill for a while I had a positive test for EBV.

I had always, since childhood, been prone to being symptomatic with every infection going and being more sick and longer than other people. That was getting worse in the 2 or 3 years before the infection that triggered my ME/CFS. Every viral infection caused a chest infection lasting an additional 2 or 3 weeks. The triggering infection was actually two infections, the second starting around two weeks after the acute symptoms of the first ebbed. Not that I was well in between. I suppose it could have been a resurgence of the 1st infection. Or this could be an example of the double assault theory.

And, to add another level of complexity, we had a long weekend in Argyll that spring. Could there have been a tick bite I didn't notice?

 

[Amw66]

I am not sure that is quite right. One screening test is for the presence of atypical large lymphocytes, which may not be completely specific but is characteristic of EBV and not designated a 'glandular fever test'. After that there are tests for rising EBV antibodies and likely PCR. Not since I was a teenager have virologists talked of 'glandular fever' as far as I know. Cytomegalovirus may produce 'mononucleosis' (the large lymphocytes) but my understanding is that it is an u common cause of clinical or pathological confusion.

I was just going by the blood test print out.
It was a line in addition to the FBC which simply said
glandular fever - positive.
ETA . I asked the GP whether this was EBV or CMV - they didn't know , just that it was " positive" for glandular fever .