CamKII & immune reaction

[peglem]

http://bloodjournal.hematologylibrary.org/...ull/112/13/4961

 

This paper is way too complicated for me to understand- but the DISCUSSION section at the end explains how CamKII is involved in autoimmunity and inflammatory processes. Would love to have Buster's (and anybody else who understands this) commentary!

[MomWithOCDSon]

http://bloodjournal.hematologylibrary.org/...ull/112/13/4961

 

This paper is way too complicated for me to understand- but the DISCUSSION section at the end explains how CamKII is involved in autoimmunity and inflammatory processes. Would love to have Buster's (and anybody else who understands this) commentary!

You certainly are . . . on a roll, that is!

 

I really appreciate it, though. The whole CamKII/memory thread begun yesterday has really gotten me going with respect to my DS; it made so many little things fall into place! But then, of course, the question is, what to do about it?!?!

 

This paper is intense! Hopefully, Buster or someone else with more science at their disposal can "water it down" for the likes of me.

 

In the meantime, I'm going to try adding taurine to DS' supplements and see what happens.

[Buster]

The article is quite good. It builds on some research from 2005 that Rifkin published around "Toll-like receptors, endogenous ligands, and systemic autoimmune disease" (for those who read such stuff : http://www3.interscience.wiley.com/journal...649336/abstract )

 

What this new article found was that certain cells that had detectors for bacteria (these detectors are known as TLR2 and TLR4) became super sensitive and produced significant inflammation (inflammatory cytokines and IFN Beta) when in the presense of sustained Cam Kinase II.

 

They found that a particular signalling pathway (known as MyD88) was being enhanced and resulted in significant amounts of pro-inflammatory cytokines (stuff that causes localized inflammation). On the other hand, there's an interesting paper elsewhere that mice who have deficient MyD88 have difficulty clearing gram-positive bacteria (see "MyD88 is required for mounting a robust host immune response to Streptococcus pneumoniae in the CNS" http://brain.oxfordjournals.org/cgi/content/full/127/6/1437).

 

This left me a bit confused. I originally thought that PANDAS kids might be deficient in MyD88 - i.e., unable to clear GABHS on their own. What this new paper indicates is that perhaps the MyD88 is working fine but something is causing sustained Cam Kinase II levels and this is causing a hyper-sensitivity to GABHS. This left me wondering if Kirvan's Auto-antibody 24.3.1 might be the cause of sustained Cam Kinase II activation and then the Cam Kinase II activation is causing MyD88 to become hyper-sensitive producing significant inflammatory cytokines. Perhaps this is the reason that the kids appear to not be able to clear GABHS and then have a hyper sensitivity.

 

There are several good new references I hadn't seen to research around siRNA. The researchers used siRNA -- a relatively recent discovery of how to block specific genes from being copied in cell creation -- to isolate and disable the Cam Kinase II activation. They found that the inflammatory cytokines were stopped when the Calcium fluxuations and Cam Kinase II activation was stopped. This indicated that CaM Kinase II is directly involved in the pro-inflammatory cytokine signalling. This does not mean that CaM Kinase II causes inflammation, but only that it is part of the signalling pathway. Think of it as a light switch -- if the Cam Kinase II switch is on then the "current" can flow through to the motor producing inflammation.

 

Most of the rest of the paper is about figuring out the specific signalling pathway that occurs and trying to confirm, refute or redraw a more accurate signalling pathway to those published by others such as:

 

On the discussion regarding autoimmune diseases and Cam Kinase II activation -- there isn't substantial new evidence there, but rather that they think the current research adds more clarity on what is happening and more research may yield insight into how the ligands (or pieces) of proteins are defeating the host-recognition mechanism and triggering auto-immune responses.

 

That's what I got out of the paper... very glad for the post -- thanks Peglem.

 

Buster

[trggirl]

Buster,

 

I totally got lost in your post (lost due to my slow brain, your post was fantastic) and will try to read it again later but in the meantime, with all the proteins and antibodies and inflammatory markers mentioned in the paper, is there anything else we can test bloodwise to help our picture of what is going on? For example can we test TLR2, TLR4, inflammatory cytokines, IFN Beta, or anything else from a blood test?

Edited April 12, 2010 by Trg girl

[JAG10]

Buster- Can you try another analogy with current, this is really hard to understand.

 

Are you saying that if we were looking at the electrical system for a house, if we plug-in the hair dryer (GABHS), that puts a lot of stress on the system. Depending on what else is on that circuit, sometimes so much stress that the breaker (CAM Kinase II) trips. In a pandas house, the wiring to the breaker (auto-antibody 24.3.1) isn't hooked up right, so the breaker isn't tripping and the house is catching on fire.

 

I'm in WAY over my head! I'm just trying to dumb it down so I can understand it.

help?

[peglem]

I'm interested in some kind of analogy that would make things clearer as well.

 

But I have another question- Is CamKII a switch for the G-protein pathways that Mary Megson talks about in this paper?

 

http://www.megson.com/readings/MedicalHypothesis.pdf

[Buster]

Buster,

 

I totally got lost in your post (lost due to my slow brain, your post was fantastic) and will try to read it again later but in the meantime, with all the proteins and antibodies and inflammatory markers mentioned in the paper, is there anything else we can test bloodwise to help our picture of what is going on? For example can we test TLR2, TLR4, inflammatory cytokines, IFN Beta, or anything else from a blood test?

 

Yes, there are such tests for the inflammatory cytokines (for example http://www.aruplab.com/guides/ug/tests/0051394.jsp) I'm not sure under what circumstances doctors order them.

 

There was a very recent paper from Swedon (http://www.americanbiotechnologist.com/blog/wp-content/uploads/2010/02/Up-regulation-of-cytokines-and-chemokines-predate-the-onset-of-rheumatoid-arthritis.pdf ) Where they found that the inflammatory cytokines predated the rheumatoid arthritis.

 

Buster

[Buster]

Buster- Can you try another analogy with current, this is really hard to understand.

 

Strangely enough good analogies are hard to create -- Let's try this one.

 

High CaM Kinase II is like a sunburn. When you now take a shower, the shower feels incredibly hot -- you are feeling the same temperature, but your temperature guage is hyper sensitive. Your clothing rubs, the finest piece of sand is agony, everything feels puffy/raw -- everything is now more sensitive. So High CaM Kinase II increases the sensitivity of the bacteria sensors making them create inflammation with the slighted provocation.

 

Hopefully I'll think of a better analogy but that's the one I'm thinking of right now -- and yes, I just got a sunburn :-)

 

Buster

[MomWithOCDSon]

Buster- Can you try another analogy with current, this is really hard to understand.

 

Strangely enough good analogies are hard to create -- Let's try this one.

 

High CaM Kinase II is like a sunburn. When you now take a shower, the shower feels incredibly hot -- you are feeling the same temperature, but your temperature guage is hyper sensitive. Your clothing rubs, the finest piece of sand is agony, everything feels puffy/raw -- everything is now more sensitive. So High CaM Kinase II increases the sensitivity of the bacteria sensors making them create inflammation with the slighted provocation.

 

Hopefully I'll think of a better analogy but that's the one I'm thinking of right now -- and yes, I just got a sunburn :-)

 

Buster

This is a great analogy, thanks Buster!

 

And it may just be odd coincidence, but we put DS on taurine (1,000 mg.) two days ago, and his sunburn seems to be settling into a nice tan of late!

[kim]

Peglem.

 

I thought this was interesting and sort of fits in with some of the info in the Megson paper, i think. I didn't reread it, but remember some of what it's about.

 

I was originally looking at this study here.

http://www.latitudes.org/forums/index.php?...amp;hl=aluminum

 

I shouldn't have said that the toll like receptors were bypassed (on the other thread) maybe they aren't stimulated ENOUGH to produce the protective effects of vit A when alum is added?

 

Anyway, just wondering if you could make anything of it in regards to CamK etc.

 

http://www.ncbi.nlm.nih.gov/pubmed/19252500

 

2009 Apr;15(4):401-9. Epub 2009 Mar 1.

 

Toll-like receptor 2-dependent induction of vitamin A-metabolizing enzymes in dendritic cells promotes T regulatory responses and inhibits autoimmunity.

 

Manicassamy S, Ravindran R, Deng J, Oluoch H, Denning TL, Kasturi SP, Rosenthal KM, Evavold BD, Pulendran B.

Emory Vaccine Center, and Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.

 

 

QUOTE

Immune sensing of a microbe occurs via multiple receptors. How signals from different receptors are coordinated to yield a specific immune response is poorly understood. We show that two pathogen recognition receptors, Toll-like receptor 2 (TLR2) and dectin-1, recognizing the same microbial stimulus, stimulate distinct innate and adaptive responses. TLR2 signaling induced splenic dendritic cells (DCs) to express the retinoic acid metabolizing enzyme retinaldehyde dehydrogenase type 2 and interleukin-10 (IL-10) and to metabolize vitamin A and stimulate Foxp3(+) T regulatory cells (T(reg) cells).

Edited April 13, 2010 by kim

[trggirl]

Ok, I am getting more and more lost with each post and each study. LOL!!!! But I know my daughter's aluminum was very high in her hair sample. So........somebody please help me. Is that a clue to an immune disorder?????????

[Fixit]

my ds had high aresenic w/i limt but higher than happy with...it stood out

 

 

Ok, I am getting more and more lost with each post and each study. LOL!!!! But I know my daughter's aluminum was very high in her hair sample. So........somebody please help me. Is that a clue to an immune disorder?????????