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

Jonathan Edwards said:
I am working on some paragraphs now. And Jo should be round for tea tomorrow!
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Any suggestions on topics for background reading/learning for those of us not versed in this stuff who want to have the best chance of understanding what you’ll be talking about?

DecodeME got me learning about DNA. This paper built on that with B cell repertoires, receptors and lifecycles as well as a bit about T cells.

It sounds as if cytokines, complement proteins/pathways and the tumour necrosis factor superfamily would be useful areas here?
 
hotblack said:
It sounds as if cytokines, complement proteins/pathways and the tumour necrosis factor superfamily would be useful areas here?
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Jonathan Edwards said:
Probably everything. But a lot of it is fairly familiar stuff and easy to follow I think.
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I think otherwise, in quite a major way! I'm really excited about your and Jo C's paper but when it appears, as things stand, I really am going to be reading it thinking, 'What? What?'

Like @hotblack, I've been mugging up on DNA (thymine! homologous! SNP!) so that I have more than a snowball's chance in hell of understanding DecodeME's results but I know zippo about any other aspect of biology. I've read everything you've said about your ideas so far and I haven't understood any of it. I don't know anything about B cells, T cells, cytokines, and whatnot except that they exist.

Should those of us crawling in the dust of ignorance be reading about immunology, generally speaking? Or cell biology? Or specific bits of both? Or something else? Maybe the things @hotblack listed?
 
@Sasha this youtube account (https://www.youtube.com/@AKLECTURES) has been a great resource for me to learn about topics in biochemistry, immunology, etc.

It's meant to be a "review series" for those studying for medical school, so all the videos are around 10 minutes each and clearly laid out (and will be marked as part of a series if the concept takes more than 10 mins to explain).

The account has hundreds of videos but usually they are well tagged in the description, so you can find a bunch of relevant videos easily if you just search something like "cytokines" or "complement system."

Often I will watch a video, it doesn't make sense immediately, but then I'll watch the next few related videos and it'll start making sense. Then I can go back to the first one and all of a sudden it clicks in my head.
 
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Jonathan Edwards said:
No, only buns and lemonade.
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Bummer. I prefer figs myself.

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Here's an association, but this specifically is only describing healthy controls. It's a positive correlation between Vitality (SF-36) and IGHV3-23/IGHV3-30. r=0.527, q=0.039. The more they have the healthier they are, so opposite direction of the association between controls and ME/CFS in the other studies.
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Edit: Data from Table 2.

Proteomics and cytokine analyses distinguish myalgic encephalomyelitis/chronic fatigue syndrome cases from controls (Giloteaux et al, 2023, Journal of Translational Medicine) Edit: S4ME
 
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I'm really interested in what is going on behind the scenes with IGHV3-30. Is anything happening? Three studies with a positive result on something so specific feels to me like an "all hands on deck" moment.

And there's a way this finding potentially relates to daratumumab. If dara works, it might be through killing abnormal B cells. And here we see something abnormal about B cells.

Sato et al are going to be measuring this in their upcoming Rituximab trial, but who knows how long until we see those results.

Apart from just retesting this in a larger cohort to confirm, the authors outlined what to do next:
Our study is limited by the small sample size and the potentially heterogeneous populations of B cells sampled.
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Sorting B cells into naive, memory, and atypical B cells prior to performing repertoire sequencing would substantially improve the inferences drawn from future repertoire sequencing studies.
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Given the emerging evidence of altered serum antibody repertoires targeting microbiome antigens (56) in ME/CFS patients, future studies should also consider sequencing IgA, as well as IgM and IgG isotypes.
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Future repertoire sequencing studies in ME/CFS where repertoires from patients and controls are sampled prior to and following vaccination could shed light on whether B-cell responses to antigenic challenge are impaired in ME/CFS.
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Maybe the grants and research are going on as we speak, as fast as the speed of science infrastructure will allow. I wish there was more action on this visible to the public though.
 
forestglip said:
I'm really interested in what is going on behind the scenes with IGHV3-30. Is anything happening? Three studies with a positive result on something so specific feels to me like an "all hands on deck" moment.
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Do you mind listing what those 3 studies were? The first thing that comes to mind to check is whether all of them were done after Covid started.
 
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