Pupil disfunction in POTS and OI

[ramakentesh]

Something to look out for as it usually suggests an autoimmune basis (Autoimmune autonomic gangliopathy with autoantibodies against nicotinic a3 autonomic acetylcholine receptors.)

 

[merylg]

I get enlarged pupils if I take Tramadol (look like a druggy!)

 

[Hip]

Something to look out for as it usually suggests an autoimmune basis (Autoimmune autonomic gangliopathy with autoantibodies against nicotinic a3 autonomic acetylcholine receptors.)

I am trying to figure out why there are so often autoantibodies against various receptors. Any ideas on this, ramakentesh?

Some autoantibodies seem to activate a receptor when they attach to it (agonize the receptor); other autoantibodies block the normal functioning of the receptor (antagonize the receptor). In either case, these autoantibodies that target receptors obviously may significantly hinder normal communications in the body (communications mediated by receptors and their ligands), and this communications dysfunction likely underlies many of the pathophysiologies of a disease.

But why, out of all the different molecular targets in the human body, do autoantibodies often target receptors?

For example, ME/CFS has autoantibodies that target the M1 subtype of muscarinic receptor, in 50% of patients. Orthostatic hypotension has autoantibodies that target both the M2 and M3 subtypes of muscarinic receptor (and in this case, the autoantibodies activate these two muscarinic receptors), as well as autoantibodies to ?1 and ?2 adrenergic receptors. Sjgren's syndrome has autoantibodies that target the M3 subtype of muscarinic receptor (and in this case, the autoantibodies block this M3 muscarinic receptor).

And you say above that POTS has autoantibodies to the A3 subtype nicotinic receptors.


I'd like to know what (pathological) processes in the body, or during an infection, set the molecular targets of autoantibodies? Knowing this may provide a way to stop the production of autoantibodies, and this could dramatically improve if not cure these autoantibody-associated diseases.

 

[fla]

What sort of pupil dysfunction? I've always been especially prone to red eyes on photographs but I assumed my retina was just more reflective than everyone else's?

 

[ramakentesh]

In this case we are probably looking for abnormal responses to light - particular in one pupil. In my case the pupils were different sizes for about two weeks unless I was in a dark room.

For example, ME/CFS has autoantibodies that target the M1 subtype of muscarinic receptor, in 50% of patients. Orthostatic hypotension has autoantibodies that target both the M1 and M2 subtypes of muscarinic receptor (and in this case, the autoantibodies activate these two muscarinic receptors), as well as autoantibodies to ?1 and ?2 adrenergic receptors. Sjgren's syndrome has autoantibodies that target the M3 subtype of muscarinic receptor (and in this case, the autoantibodies block this M3 muscarinic receptor).

Are you referring to the work of David Kem et al on Orthostatic hypotension? Previously all of the work I was aware of was looking at autoantibodies that bind to or block a3 acetylcholine receptors in POTS, OH and in Sjorgens Syndrome. Can you refer me to the research that talks about muscarinic receptors? Other than perhaps mediating vasodilation I am confused about how muscaranic receptors would effect autonomic control as they are generally not ganglionic. i guess vasodilation?

Doc have also looked into autoantibodies against Norepinephrine transporter, beta 2 activating or binding, and perhaps ang II receptor binding but apparently finding autoantibodies does not automatically prove a conclusion that they have a pathological role in a disease state even when it involves those receptors.

As for why - gees if they knew that you'd be seeing some pretty impressive treatments for all autoimmune disease right across the board. Its alwasy the same situation - loss of self tolerance and then different arms of the immune system perpetually attacking specific targets - the targets being the main delineator of the disease.

Molecular mimicry is a popular possibility on patient discussion and some research theory - at least for Ankylosing Spondylitis. A bacteria enters the body that has the ability to trick a suspectible host into attacking antigens in the body that are similar to those attached to the bacteria. Much of the newer reseatch also points to a poor immune system going crazy because it cannot competantly rid the body of certain pathogens that contain proteins similar to the patient's histocompatibility.

 

[ramakentesh]

I found it - thanks for the tip:

http://www.ncbi.nlm.nih.gov/pubmed/12851722

 

[Hip]

Can you refer me to the research that talks about muscarinic receptors? Other than perhaps mediating vasodilation I am confused about how muscaranic receptors would effect autonomic control as they are generally not ganglionic. i guess vasodilation?

Yes. I put these references in an earlier thread on acetylcholine and the parasympathetic nervous system.

As for why - gees if they knew that you'd be seeing some pretty impressive treatments for all autoimmune disease right across the board. Its alwasy the same situation - loss of self tolerance and then different arms of the immune system perpetually attacking specific targets - the targets being the main delineator of the disease.

Molecular mimicry is a popular possibility on patient discussion and some research theory - at least for Ankylosing Spondylitis. A bacteria enters the body that has the ability to trick a suspectible host into attacking antigens in the body that are similar to those attached to the bacteria. Much of the newer reseatch also points to a poor immune system going crazy because it cannot competantly rid the body of certain pathogens that contain proteins similar to the patient's histocompatibility.

I find the idea that microbes trick the host into attacking antigens in the body quite interesting; there are a lot of tricks that microbes employ for immune evasion purposes (immune evasion = thwarting the action of the immune system, to ensure the survival of the microbe), and autoimmune attacks might just be one of their more clever immune evasion tricks.


I am particularly interested in enteroviruses in ME/CFS (and its co-morbid diseases like POTS). Autoimmunity can appear within hours of the initial enterovirus infection, and its appearance seems to be driven by certain key cytokines, such as IL-1? and TNF-?. Ref: here.

Perhaps inhibiting IL-1? and TNF-?, even after autoimmunity has begun, may help reverse it?

 

[ramakentesh]

yeah that is what I am looking at also because i have Ank Spond.

 

[Hip]

In which case, you might be interested in the list of TNF-alpha inhibiting supplements I compiled. I did some experiments a while back taking lots of these TNF-alpha inhibiting supplements simultaneously.

Supplements that inhibit TNF-alpha:


Cat's claw - a remarkably potent inhibitor of TNF-alpha production

5-Loxin extract from Indian Frankincense (Boswellia Serrata) is a very potent inhibitor of TNF-?

Acetylcholine significantly inhibits the release of TNF (so acetylcholine boosters like choline bitartrate, alpha GPC, carnitine may well reduce TNF. However, "piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine")

Astragalus
Burdock (Arctium lappa)
Ginger
N-acetyl-l-cysteine
Chondroitin sulfate
Devil's Claw
Curcumin
Milk thistle
Alpha lipoic acid
Allicin (from Garlic)
Stinging nettle leaf
Magnesium
Vitamin C
ECGC Green Tea
Vitamin E
Tea tree
Ashwagandha
Rehmannia root
Coptis root
Anethole (in fennel)
Frankincense
Xylitol
Fish Oil (Omega-3)
Oxymatrine
Artesunate
Dietary fiber
Colostrum: Soluble TNF-? receptors in human colostrum neutralize TNF-? bioactivity
Niacinamide
Benicar
Quinine
Naltrexone
Deprenyl
Azithromycin - selectively reduces TNF-alpha levels in cystic fibrosis airway epithelial cells
Royal Jelly
Oregano
Gingko
Licorice
Clove
Q10 - a moderate anti-inflammatory effect
Evening primrose oil (gamma-linolenic-acid) - converts to Prostaglandin E1, which suppresses TNF-alpha


The Following Supplements INCREASE production of TNF-alpha:

Reishi mushroom
Rhodiola rosea
Elderberry juice (Sambucol)
Chlorella
Spirulina
Ginseng
Dandelion root
Honey
Chocolate
Echinacea
Silica
Lactoferrin
Biotin deficiency - up-regulates TNF- production in murine macrophages

 

[fla]

I found it - thanks for the tip:

http://www.ncbi.nlm.nih.gov/pubmed/12851722

Interesting, the Muscarinic acetylcholine receptor M1 is related to stomach acid secretion and low stomach acid is related to vitiligo which a subset of us also have. I remember Montoya bringing up vitiligo in one of his videos. Someday all of these clues will fit nicely together.

 

[ramakentesh]

I am very interested so thank you very much Hip! And I have some experiences with many of those:

Licorice improves both my POTS and my AS
Rehmannia improves my POTS
Rhodiola rosea improves my POTS for about two days before ALWAYS bringing on a massive relapse of AS - which may tie in with your observations.
Astralagus helps both POTS and AS for me.
Stinging nettle tea works wonders for AS but seems to bring on POTS for me although this could be random
Similarly, ginger lowers my BP and Curcumin makes POTS much worse for me.

I guess ill find the balance one day!