Genetics: HLA-DQA*05:01

Adding on to this, from Mella and Fluge's CycloME paper:

Frequency of HLA risk alleles (HLA DQB1*03:03 and/or HLAC*07:04) in responders and non-responders during follow-up. P-value from
Fischer’s exact test. HLA, Human Leukocyte Antigen

This was decently predictive of response rate in the paper, those HLA risk positive had a 10 responder to 1 non responder rate and those positive had a 11 responder to 29 non responder rate.

However we are talking about HLA DQA here so I don't know the difference.

But in general I am skeptical about DecodeME or genetics as I don't see how it would impact treatment or intervention. But i dont know much either
 
ryanc97 said:
Frequency of HLA risk alleles (HLA DQB1*03:03 and/or HLAC*07:04) in responders and non-responders during follow-up.
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Yes, the same two alleles that were risk alleles for ME/CFS in this other study:

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Fluge, Mella et al 2020

I feel like I must be missing something, because why was there never much interest in this? What's the chance of the same exact two alleles, out of the dozens possible, being significant in both?

I never looked deeply into it, but maybe the populations overlap so it's not a true replication.
 
forestglip said:
Yes, the same two alleles that were risk alleles for ME/CFS in this other study:

Human Leukocyte Antigen alleles associated with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Fluge, Mella et al 2020

I feel like I must be missing something, because why was there never much interest in this? What's the chance of the same exact two alleles, out of the dozens possible, being significant in both?

I never looked deeply into it, but maybe the populations overlap so it's not a true replication.
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I have no idea, but from my PoV, the only useful thing this is, is that if you wanna order Cyclophosmamide from Indiamart, you might wanna test for this gene somehow, if you don't have it, then you can take the Cyclo.
 
Hoopoe said:
That strikes me as unintuitive.

ME/CFS is triggered by a variety of pathogens and my intuition tells me that while specific genetic vulnerabilities for ME/CFS would certainly exist for each of these pathogens, they wouldn't be among the top hits in a GWAS. Variants related to disease process would dominate because these are what ME/CFS patients tend to have in common.

Maybe my mental model is wrong. I'm just an amateur that can't stop thinking about these things.
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It's a distinction that can't be easily made, because there are parts of the immune response that are going to be pathogen-specific and parts that are going to be generally anti-viral/anti-bacterial, etc. There's also differences in general cell susceptibility to infection that is somewhat independent of an immune system response, which is what the RABGAP1L finding speaks to. It's been found to be relevant in influenza and strep because it was studied in those contexts, but many viruses use those same mechanisms to infect cells.

So, long story short, it's very possible to have genetic hits that confer broader anti-viral protection (to an extent, since none of those genes are going to be fully protective against infection). And it's also important to keep in mind that the odds ratios are very slim for all the hits--increased susceptibility to just one class of pathogens may still be driving the hit.
 
ryanc97 said:
I have no idea, but from my PoV, the only useful thing this is, is that if you wanna order Cyclophosmamide from Indiamart, you might wanna test for this gene somehow, if you don't have it, then you can take the Cyclo.
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I don't think we can say that, or give the impression it's safe for untrained people to experiment on themselves with a drug known to be associated with cancer. Or any drug, for that matter.
 
Kitty said:
I don't think we can say that, or give the impression it's safe for untrained people to experiment on themselves with a drug known to be associated with cancer. Or any drug, for that matter.
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Yeah I don't think it's safe but it's something I might put on my try list.
 
Fair, I'm just stating what I should do. It's just my risk appetite is quite high. I know it is a powerful chemo drug. It would be a last resort for me if everything else didn't work. I'm quite sure everyone knows it's very risky.

But back to the point, it would seem based on the data the gene HLA DQB1*03:03 and/or HLAC*07:04 is fairly predictive of response on cyclophosphamide, that's my point. Why I have no idea.
 
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Jonathan Edwards said:
I am tempted to think that if anything a DQ signal is nudging things towards the more innate side of T cell recognition, which can use DQ, as seen with MAIT cells and gamma delta cells. It may just indicate a non-specific threshold effect due to perhaps binding outside of the traditional active site but even if it just does that it maybe should not be ignored.
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I think that story might tie in well with the BTN2A2 and BTN3A3 seem to have a similar role in gamma delta T cells.
 
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