Gene CTLA4 or CTLA-4 can downregulate T-lymphocyte immune responses which may also keep CD57 low

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astroman
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   Posted 2/17/2018 2:53 PM (GMT -6)   
Did a little research here on genes, low cd57 and low T cells. This is what I came up with:

CTLA4 or CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), also known as CD152 (cluster of differentiation 152), is a protein receptor that, functioning as an immune checkpoint,
downregulates immune responses............................

The mechanism by which CTLA-4 acts in T cells remains somewhat controversial. Biochemical evidence suggested that CTLA-4 recruits a phosphatase to the T cell receptor (TCR), thus attenuating the signal.":
/en.wikipedia.org/wiki/CTLA-4


This might be why some never achieve normal elevated cd57 values. CD57 also measures T cells (test flaw), not just Natural Killer cells. Low T cells from this gene can lower CD57test.


"CD57 was initially used as a marker for NK cells, but it is not expressed by all NK cells and is also expressed by T-cell subpopulations.":
cvi.asm.org/content/16/8/1249.full


Its a fact that Lyme alone can lower T cells. But, if you have this "switchable" gene and it was already "expressed"- this might have previously lowered your T cells (immune defense), possibly being WHY you developed lyme symptoms.

Post Edited (astroman) : 2/19/2018 10:52:27 PM (GMT-7)


astroman
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   Posted 2/17/2018 4:09 PM (GMT -6)   
HSP90 up-regulates the CTLA4 gene controlled T- cells. Its used for that in cancer immunotherapy.

/www.nature.com/articles/s41467-017-00449-z
Had initial lyme symptoms late 80's, then again and with bullseye early 90's. Ended ABX for Lyme in 2015. Rebuilding / fine tuning / fixing muscles since then; member "10 Percenters Lyme Club". What an adventure this has been. Hashimotos adds to the enjoyment.

astroman
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   Posted 2/18/2018 12:37 PM (GMT -6)   
There were people wondering about cd-57 this last month. Usually newbies asking about that, 23andme reviles this gene.

My hypothesis here: if you dont have this gene defect cd57 is more likely work for improvement tracking.

Post Edited (astroman) : 2/18/2018 11:40:04 AM (GMT-7)


mpost
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   Posted 2/19/2018 1:00 AM (GMT -6)   
thanks for the effort, but this makes absoluelty no sense to me. i started the jurney sick as a dog with CD57 164 and i am close to ending it with almost no symptoms left, so 99% recovered, with CD57 of 72.... after 6+ months of antibiotics, that...again, were VERY effective in my case....

disclaimer: i have had the same genes the whole time smile

Girlie
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   Posted 2/19/2018 1:26 AM (GMT -6)   
mpost said...
thanks for the effort, but this makes absoluelty no sense to me. i started the jurney sick as a dog with CD57 164 and i am close to ending it with almost no symptoms left, so 99% recovered, with CD57 of 72.... after 6+ months of antibiotics, that...again, were VERY effective in my case....

disclaimer: i have had the same genes the whole time smile


I think that's why some LLMD's don't bother with the cd57.
Dr. J.'s clinic hasn't mentioned I get that test done...and I've got a whack of blood work they want me to do.

Anyone know if Dr. H. uses cd57 to assist in gauging improvement?
Moderator, Lyme Forum
Symp started April/2013; Buhner's Lyme May 15-July24/14; Igenex pos. July 3/14
Doxy: July 4-Aug.24/14;Zithro July26-Aug24/14; Amox + Proben. Aug. 29/14;
added biaxin Sept. 26/14
Disc. amox,added Ceftin Nov. 20th.;
Disc. biaxin added Buhner bart herbs Dec/14;Jan/15 pulsing Tinda (w/ Ceftin);
Abx/herb break Apr-July/15; July-mino; Aug. added Rif;
Nov./15 mino - to biaxi

Georgia Hunter
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   Posted 2/19/2018 3:46 AM (GMT -6)   
CD57 is a gauge, but it's a faulty gauge. Since most of us aren't dealing with one pathogen, we can have therapeutic success and gain normal function but still have low CD57 numbers. This is likely due to undetermined pathogens. Protozoans are bad about suppressing immune response and lowering T cell formation. It is accomplished through MTRR mutations as well as other epigenetic shifts in the one carbon metabolism chain. I haven't seen a test for protozoans that was worth a flip so they go undetected.

The more I study, the more I see our problems as simply a reduction in nutrients/vitamins and an altering of our GI flora. This snowballs into the problems we face.

astroman
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Date Joined Mar 2014
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   Posted 2/19/2018 11:19 PM (GMT -6)   
mpost said...

disclaimer: i have had the same genes the whole time


Maybe this makes more sense- Known genes that can cause health issues depend on if they were "expressed" or "switched" (as Wiki likes to call it). "Activated" sounds better to me. So if this gene was activated, your T cells can be compromised.

Note: These are somewhat different than your genes responsible for your hair, skin and eye color ect.
Funny, I read there is not a gene for red hair, but one which prevents it. People missing this gene have red hair by default.

Long story short, according to the links I provided in the post: a low T-cell count might "pull down" your CD57 Natural Killer cell count. This can be one reason the cd57 test is unreliable- because it also counts T-cells.

So this is part is just my thinking: adding the info together from the above two links, its could be possible that if you have this gene (and I suppose the one Hunter also mentioned), and it was expressed from the challenge of lyme treatment or other stress, pathogens ect (we get worse before better) your T cells are now lower pulling your CD57 value down.

Maybe in time, if whatever made your T cell gene switch is resolved, your T cells will go up bringing CD57 up with it.

T-cell strength against lyme BB bacteria, or maybe "response" for a better word, can be measured by the i-Spot test from Wisconsin. They even say this value can be lower than normal in chronic lyme- so much that its no longer able to do its job. They prove this time and time again. I have read other opinions on this, but since this lab specializes in this topic, they prob know what they are doing so I tend to believe them.

Post Edited (astroman) : 2/19/2018 10:54:07 PM (GMT-7)


Georgia Hunter
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   Posted 2/20/2018 5:47 AM (GMT -6)   
Astro, you are correct. Our body prioritizes its functions. As an example, there are two functions that are more important than just about anything and get priority. Those functions are buffering acids and making DNA. We know chronic inflammation causes an increased acidity in the body so the body diverts more resources to alleviate that problem. People with chronic inflammation also have a decrease in one carbon metabolism. It is often due to insufficient cofactors and substrates and this causes epigenetic shifts in our methylation genes which reduces T cell formation. The basic chemical structures of DNA used to make T cells, and all cells for that matter, are purines and pyrimidines. T cells are not as high a priority as other cells so the pyrimidines are used for other things rather than making T cells.

Pyrimidines are broken down into carbon dioxide, beta-alanine, and ammonia where purine rings are broken down into uric acid. Uric acid is a free radical scavenger and scavenging free radicals is very high on the body's priority list. Ammonia buffers acid. So an increased rate of pyrimidine and purine breakdown would help reduce problems Lyme patients are suffering from. This would lower T cell formation but the body does it on purpose.

Pyrimidines contain a pyridine ring that is formed from nicotinic acid (niacin.) This can also be made from mycobacterium, E coli, and several other gram negative bacteria. So reducing these bacteria can reduce the pyridine formation which can reduce pyrimidine formation which can reduce ammonia as a by-product. Pyridines also act as electrophiles to scavenge for free radicals. If they do this, they aren't helping to make DNA or T cells.
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