IVIG article

[peglem]

http://bloodjournal.hematologylibrary.org/...full/115/9/1663

 

I almost understand this one!

[Buster]

http://bloodjournal.hematologylibrary.org/...full/115/9/1663

I really like this article, what I got was the following:

1. Auto-antibodies mark a cell for consumption by macrophages
   
2. When a Macrophage consumes the cell, it keeps the tag of the auto-antibody
   
3. The tagged macrophage runs into an appropriate T-cell and activates the T-cell
   
4. The activated T-cell runs into a B-cell and causes production of more auto-antibodies
   
5. And the cycle repeats (got to step 1)
   

What's interesting with GABHS (and some other diseases) is that the exotoxins to strep can activate non-specific T-cells (i.e., that the T-cells get activated whether the specific antigen is present or not). Normally, this isn't a problem because the antibodies don't find anything to bind to and die off. However, if they are anti-host and find a binding site, then this can cause the feedback problem where the immune system goes nuts again.

 

The paper then indicates that IVIG works by either:

1. Saturating all the Fc receptors on the APCs so APC never presents the auto-antibody
   
2. Binding to a suppressor mechanism (currently unknown) that prevents the APC from presenting any auto-antibodies
   
3. Binding to Fc receptors on the endothelial cells so auto-antibodies have no place to attach and die
   

(a) makes the most sense to me -- but who knows.

 

Buster

[peglem]

http://bloodjournal.hematologylibrary.org/...full/115/9/1663

I really like this article, what I got was the following:

1. Auto-antibodies mark a cell for consumption by macrophages
   
2. When a Macrophage consumes the cell, it keeps the tag of the auto-antibody
   
3. The tagged macrophage runs into an appropriate T-cell and activates the T-cell
   
4. The activated T-cell runs into a B-cell and causes production of more auto-antibodies
   
5. And the cycle repeats (got to step 1)
   

What's interesting with GABHS (and some other diseases) is that the exotoxins to strep can activate non-specific T-cells (i.e., that the T-cells get activated whether the specific antigen is present or not). Normally, this isn't a problem because the antibodies don't find anything to bind to and die off. However, if they are anti-host and find a binding site, then this can cause the feedback problem where the immune system goes nuts again.

 

The paper then indicates that IVIG works by either:

1. Saturating all the Fc receptors on the APCs so APC never presents the auto-antibody
   
2. Binding to a suppressor mechanism (currently unknown) that prevents the APC from presenting any auto-antibodies
   
3. Binding to Fc receptors on the endothelial cells so auto-antibodies have no place to attach and die
   

(a) makes the most sense to me -- but who knows.

 

Buster

Thanks, Buster. You made my fuzzy sort-of-understanding much clearer!

[kimballot]

Thanks Buster - between your description and the diagram I think I am getting something logged into my brain. I do have a question, though, about the endothelial cell in option C - Where did that come from and why are the autoantibodies NOT binding to the APC once the IgG binds to the endothelial cell? Sorry - I am trying to understand this better. Thanks

 

The paper then indicates that IVIG works by either:

1. Saturating all the Fc receptors on the APCs so APC never presents the auto-antibody
   
2. Binding to a suppressor mechanism (currently unknown) that prevents the APC from presenting any auto-antibodies
   
3. Binding to Fc receptors on the endothelial cells so auto-antibodies have no place to attach and die
   

(a) makes the most sense to me -- but who knows.

 

Buster

Edited April 20, 2010 by kimballot

[peglem]

What is the IfF?

[kimballot]

Oops - I was typing too fast without looking - I meant to say IgG - I will go back and edit. Thanks!

[Buster]

Well, the theory is that the endothelial cell is what is being "consumed" by the macrophage. So if you prevent any of the auto-antibodies from binding to the endothelial cell than then macrophage or APC can't present the antibody -- i.e., the macrophage can't consume the endothelial cell and present any antigen.

 

Buster

 

Thanks Buster - between your description and the diagram I think I am getting something logged into my brain. I do have a question, though, about the endothelial cell in option C - Where did that come from and why are the autoantibodies NOT binding to the APC once the IgG binds to the endothelial cell? Sorry - I am trying to understand this better. Thanks

The paper then indicates that IVIG works by either:

1. Saturating all the Fc receptors on the APCs so APC never presents the auto-antibody
   
2. Binding to a suppressor mechanism (currently unknown) that prevents the APC from presenting any auto-antibodies
   
3. Binding to Fc receptors on the endothelial cells so auto-antibodies have no place to attach and die
   

(a) makes the most sense to me -- but who knows.

 

Buster

[Alex]

How about adding this paper to the research section of the pinned information. I would have liked to have had this when trying to explain to our pediatrician how IVIG might work for PANDAS.

 

Alex

[melanie]

http://bloodjournal.hematologylibrary.org/...full/115/9/1663

 

I almost understand this one!

bump

[trggirl]

So how doess the CamKinase II, which is becoming the marker for PANDAS, tied into this?

 

I know I keep going back to the CamKinase repeatedly, and I apologize for that, but I am desperately trying to tie it into PANDAS since that is the only elevated marker I have.

[Fixit]

So how doess the CamKinase II, which is becoming the marker for PANDAS, tied into this?

 

I know I keep going back to the CamKinase repeatedly, and I apologize for that, but I am desperately trying to tie it into PANDAS since that is the only elevated marker I have.

 

i didn't even have that to start....it was marginal at 105....

but as a mom i've seen too many illnesses then exasperations....and ds was sick the day before this onset...

then found this january, myco p igg to be 637...scale ends at 310...

so it makes me think that myco p may have been the trigger..now his body is in perminent over drive...

cam now 160, but also his urinary neoptrens are scarey high....which is a marker for hiv, autism, ms, lupus......

i wonder if urinary neoptrins should be tested for more pand/pits as a autoimmune marker.....

waiting for another round of same labs to come back...i wouldn't doubt that maybe the igg for myco came down...

his body is just in overdrive and can't stop....

[peglem]

So how doess the CamKinase II, which is becoming the marker for PANDAS, tied into this?

 

I know I keep going back to the CamKinase repeatedly, and I apologize for that, but I am desperately trying to tie it into PANDAS since that is the only elevated marker I have.

There is SOMETHING overstimulating a receptor(s) on nerve cells creating all that x-tra CamK activity. Maybe its not a strep derived auto-antibody, or maybe there are more of those that haven't been found yet. Maybe its antibodies to other pathogens... this is why Cunningham's work is so important- we need the answers!

[peglem]

oops! posted in wrong place.

Edited February 8, 2012 by peglem