Antibodies to ß adrenergic and muscarinic cholinergic receptors in patients with CFS

[Marky90]

Would IVIG or steroids (like Predislone) be useful against the antibodies?

It provides symptom relief in some patients, yes.

 

[deleder2k]

Would IVIG or steroids (like Predislone) be useful against the antibodies?

Plasmapheresis, IVIG and Prednisolone could all be beneficial.

 

[msf]

It would be good to know whether the Ritux cases showed a preponderance of major or minor responders.

 

[alex3619]

Is this the Holy Grail we have been looking for, at least for a subset?

Its early days yet, and association is not causation, but its a darn good place to start. Furthermore it may mean finding grant money for looking for more autoantibody types that much easier to get.

This does not identify responders and nonresponders. What it does is show that patients with particular autoantibodies may respond. The fact that nonresponders did not show an antibody decline might however mean they are justified in repeated treatment until they do respond.

It is however one of the most encouraging pieces of research all year!

One thing it might mean is that ME is not one disease, but characterized by different combinations of autoantibodies. This is just speculation at this point, but its looking more likely.

Its analogous in a way to how brain disorders may be misclassifications. How the brain is affected is probably a many dimensional problem. Not just dysfunction but specific location of disfunction matters. A shift in just a millimeter one way or another may change the symptoms. Indeed, ME may suffer this problem too as different vascular capacities in different places in the brain may lead to different symptoms.

I am a nonstandard type 2 diabetic. I met the technical criteria but my blood tests never looked like they were supposed to once you went to secondary tests. This might go a long way to explaining why.

Well, we might have screwed up lives. We might have had whole life experiences slip past us. We definitely got to see the dark side of exhaustion, pain and brain dysfunction. Yet how many others ever get to understand what it is like to watch the answers unfold to the greatest mystery of our lives?

 

[deleder2k]

Hear, Hear, @alex3619!

 

[Gijs]

Yes Alex, it is for a subgroup! And these findings make sence. I think a low dose of prednison will help but prednison is a very bad drug for the longterm.

 

[Valentijn]

Can anyone figure out the rates of the types of auto-antibodies in patients compared to controls?

 

[msf]

Someone remind me, have the Ritux studies shown a correlation between responder status and the level and duration of B-cell depletion?

 

[Marky90]

Well spoken @alex3619 ! This indicates for me that within the ME-patient population, there lies various undiscovered autoimmune diseases.

 

[deleder2k]

Yes Alex, it is for a subgroup! And these findings make sence. I think a low dose of prednison will help but prednison is a very bad drug for the longterm.

I don't think low dose work... I have had 120mg methylprednisolon IV. It didn't work.. In MS they use 3g over 3 days with prednisolon. 5 mg daily won't do it..

 

[Sidereal]

Rituximab responders vs. non-responders:

 

[alex3619]

I don't think low dose work... I have had 120mg methylprednisolon IV. It didn't work.. In MS they use 3g over 3 days with prednisolon. 5 mg daily won't do it..

To stop autoimmune problems with drugs like this you need very high immune suppressing doses. Which is very damaging over time. How many know that drugs like this were the first line of treatment in some parts of the world in the late 70s? My aunt got something that I would call CFS after contracting Ross River virus (we lived on the banks of that river!). She was on high dose cortisol until they had to stop treatment due to side effects. These treatments suppress the problem, but do not eliminate the problem.

PS Low dose use of these kinds of drugs have hormone replacement effect, not immune suppression. Its a different use of the drug.

 

[Marky90]

To stop autoimmune problems with drugs like this you need very high immune suppressing doses. Which is very damaging over time. How many know that drugs like this were the first line of treatment in some parts of the world in the late 70s? My aunt got something that I would call CFS after contracting Ross River virus (we lived on the banks of that river!). She was on high dose cortisol until they had to stop treatment due to side effects. These treatments suppress the problem, but do not eliminate the problem.

PS Low dose use of these kinds of drugs have hormone replacement effect, not immune suppression. Its a different use of the drug.

Yeah, i would be more scared of long term steroid use compared to rtx if i`m honest.

 

[alex3619]

Someone remind me, have the Ritux studies shown a correlation between responder status and the level and duration of B-cell depletion?

I think this was discussed on another thread. I think the answer is no. Its about antibody suppression, not B cell suppression itself. The drug suppresses B cells in all patients, but may not target plasma cells effectively. Hence some plasma cells may lurk and need repeated treatment, or alternative treatment, but this is not easy to show - its inferred.

 

[Sidereal]

Steroids are not a viable solution. Just ask lupus patients what long-term immunosuppressive doses of prednisone are like.

 

[Marky90]

I think this was discussed on another thread. I think the answer is no. Its about antibody suppression, not B cell suppression itself. The drug suppresses B cells in all patients, but may not target plasma cells effectively. Hence some plasma cells may lurk and need repeated treatment, or alternative treatment, but this is not easy to show - its inferred.

Do you know if there`s currently anyway to locate these "rogue" plasma cells?

 

[jimells]

What's that crackling sound in the distance? Is it... could it be... the Humpty Dumpty of Psychobabble has taken a great fall?

And look... all the King's Horses and Sir Simon's Men couldn't put Humpty together again...

 

[Riley]

Antibodies against ß2, M3 and M4 receptors were significantly elevated in CFS patients compared to controls.

We provide evidence that 29.5% of patients with CFS had elevated antibodies against one or more M acetylcholine and ß adrenergic receptors

Are they saying that 29.5% of the 268 CFS patients studied had elevated antibodies?

 

[DanME]

M3 Receptor:

"However, with respect to vasculature, activation of M3 on vascular endothelial cells causes increased synthesis of nitric oxide, which diffuses to adjacent vascular smooth muscle cells and causes their relaxation and vasodilation."

"The muscarinic M3 receptor regulates insulin secretion from the pancreas[4] and are an important target for understanding the mechanisms of type 2 diabetes mellitus."

"The M3 receptors are also located in many glands, both endocrine and exocrine glands, and help to stimulate secretion in salivary glands and other glands of the body. Other effects are: Increased secretions from stomach, Eye accomodation."

Directly linked to NO syntheses and insulin secretion. Very interesting!!!

 

[DanME]

M4 seems to be a bit ominous. Only found in the brain, seems to be involved in extrapyramidal motor control via dopamine.