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Research: Neuronal recognition by CD8 T cells elicits central diabetes insipidus.

CBS

Senior Member
Messages
1,522
Perhaps a mechanism by which autoimmunity leads to fluid loss, hypovolemia and POTS/OI.

I should note that this article was first brought to my attention by another PR member (whom I would gladly acknowledge but I don't have their permission to do so). I've been away for a while and am just getting back to PR. Thanks to "you know who you are."


Cutting edge: Neuronal recognition by CD8 T cells elicits central diabetes insipidus.

Scheikl T, Pignolet B, Dalard C, Desbois S, Raison D, Yamazaki M, Saoudi A, Bauer J, Lassmann H, Hardin-Pouzet H, Liblau RS.

J Immunol. 2012 May 15;188(10):4731-5. Epub 2012 Apr 13.

Abstract

An increasing number of neurologic diseases is associated with autoimmunity. The immune effectors contributing to the pathogenesis of such diseases are often unclear. To explore whether self-reactive CD8 T cells could attack CNS neurons in vivo, we generated a mouse model in which the influenza virus hemagglutinin (HA) is expressed specifically in CNS neurons. Transfer of cytotoxic anti-HA CD8 T cells induced an acute but reversible encephalomyelitis in HA-expressing recipient mice. Unexpectedly, diabetes insipidus developed in surviving animals. This robust phenotype was associated with preferential accumulation of cytotoxic CD8 T cells in the hypothalamus, upregulation of MHC class I molecules, and destruction of vasopressin-expressing neurons. IFN-γ production by the pathogenic CD8 T cells was necessary for MHC class I upregulation by hypothalamic neurons and their destruction.
This novel mouse model, in combination with related human data, supports the concept that autoreactive CD8 T cells can trigger central diabetes insipidus.
 

adreno

PR activist
Messages
4,841
Not much you can do if your vasopressin-expressing neurons are destroyed. Bummer.
 

CBS

Senior Member
Messages
1,522
Not much you can do if your vasopressin-expressing neurons are destroyed. Bummer.

No disrespect intended but I strongly disagree.

See: Desmopressin acutely decreases tachycardia and improves symptoms in the postural tachycardia syndrome.


Desmopressin (DDAVP); practically no side effects if used appropriately, potential in many patients for near complete alleviation of many classic "CFS" symptoms, particularly some of the most life altering symptoms.

Personally, I believe treatment of hypovolemia in may be a necessary first step in stabilizing ME patients so that they can tolerate more aggressive therapies such as anti-virals. I suspect that that failure to address (or even recognize) hypovolemia first leaves the patient with a weakened system when stronger overall health would lead to greater treatment success across a number of modalities.

The first goal of treatment should always be to stabilize the patient. hydration and delivery of oxygen and nutrients are all vital functions. Without stabilizing these essential functions, all other efforts are compromised.
 

adreno

PR activist
Messages
4,841
No disrespect intended but I strongly disagree. Desmopressin (DDAVP); practically no side effects if used appropriately, potential in many patients for near complete alleviation of many classic "CFS" symptoms, particularly some of the most life altering.
Right, but there is no way of curing it.
 

CBS

Senior Member
Messages
1,522
While having to keep my desmopressin close at hand, I find it a small price to pay for the huge benefits I have derived from 0.5 mg /day since January, 2009.

Without it I suspect I would have failed on both Valcyte and Equilibrant. As it is, I was functioning at 1 of 10 (bed-bound, little, if any, self care, lights off, NO SOUND; as close to death as I can imagine). I'm now at a solid 7/10 on a daily basis and recovering regularly from activities I didn't dare dream of at the time.

Not a cure but I honestly do not expect a cure in my life time (although I'd take one). I've had this for eighteen years and reversing the downward death spiral of ME was huge.
 

Enid

Senior Member
Messages
3,309
Location
UK
What particularly rings bells for me here CBS is cytotoxicity and acute but reversible encephalomyelitis, recalling recognition and memory loss (even passing out) and yet memory, vocabulary, mental speed up slowly returned - it took some effort - general recognised ME supps etc. but it all returned. But muscles less easily and described here (UK) as reactive arthritis only, though MS and myelin sheath damage suspected.
 

CBS

Senior Member
Messages
1,522
What particularly rings bells for me here CBS is cytotoxicity and acute but reversible encephalomyelitis, recalling recognition and memory loss (even passing out) and yet memory, vocabulary, mental speed up slowly returned - it took some effort - general recognised ME supps etc. but it all returned.

I had a similar thought. And while my cognition has improved dramatically with desmopressin (and valcyte), I recently required a small increase in my dose in order to keep my fluid loss under control. I recently had a visit with my pituitary specialist and I asked him about desmopressin metabolism/excretion. He said that while he was not clear on the exact mechanism, a pattern of needing to increase dose with increases in activity levels was common amongst diabetes insipidus patients.
 

Enid

Senior Member
Messages
3,309
Location
UK
I probably have some level of diabetes too (have to rush and eat a biscuit periodically after activity) - it's an auto-immune state ME tips into .... one day soon this immune system crash (pathogen or what) will be revealed. Glad you have specialists to aid you there - too confusing for Docs here. And surely glandular treatments can only aid as your Docs discover you need - important part of it all.
 

CBS

Senior Member
Messages
1,522
I probably have some level of diabetes too (have to rush and eat a biscuit periodically after activity) - it's an auto-immune state ME tips into .... one day soon this immune system crash (pathogen or what) will be revealed. Glad you have specialists to aid you there - too confusing for Docs here. And surely glandular treatments can only aid as your Docs discover you need - important part of it all.

Hi Enid,

Just to be clear, diabetes (melllitus - type 1 or type 2) is an illness that is distinct from diabetes insipidus. The characteristics shared by the two (in a majority of cases) are a high rate of fluid loss and increased thirst; this is where the word diabetes was derived ("to go through, pass over"). Diabetes mellitus is caused by a lack of insulin production (type-1) or insulin resistance (type 2).

Diabetes insipidus is an inability to "concentrate urine" which means that your body is losing a significant amount of fluid relative to what you are taking in (compensatory increased thirst is common but in some cases the "thirst mechanism" in the hypothalamus is also damaged). Central diabetes insipidus is caused by the absence of a sufficient amount of vasopressin, this prevents the kidneys from conserving fluids by shunting filtered fluid back to the blood stream (forgive me for the abbreviated description) and results in a high volume of fluid loss (typically greater than 3000 ml/day and the resultant low sodium concentration).

I hope this helps.

Shane
 

Enid

Senior Member
Messages
3,309
Location
UK
Thanks Shane - I had all that at one stage too but has cleared now (dire thirsts increase water intake didn't solve, frequent urination and sometimes clear in colour, sometimes neon orange - leaching out potassium). It has resolved and I hope with your Doc's treatment yours will too. Some damage in the hypothalmus rings bells for me - much spoken of and co-morbids at that time - bod's regulatory systems lead me to suspect it in my case. But it's reversible - how I don't know but on a battery of ME support supps. You can be more accurate with your specialists there.

I'll certainly look into the useful information you have given now.