Question re: BBB and Symptoms

[DaleS]

Buster,

Thanks for this explanation, again, but what I would like to know is if there are other theories regarding the mechanism of BBB breach and neural tissue inflimation.

Early this month, our dd had her first IVIG with Dr. K and we asked him about this. He indicated that your description is only one theory and that he believed that there may be another mechanism. I didn't understand everything he said (partially due to his accent) but his description had something to do with the antibodies causing the BBB breach and allowing other invaders through to cause neural inflammation. Any comments on other theories would be appreciated.

Edited July 3, 2010 by DaleS

[TessaKrista]

Couldn't children just go on an anti-inflamatory drug to help with the inflamation? There has got to be a reason why this solution isn't proposed as the only solution. Why is that do you think?

[kimballot]

Couldn't children just go on an anti-inflamatory drug to help with the inflamation? There has got to be a reason why this solution isn't proposed as the only solution. Why is that do you think?

 

 

Yes - anti inflammatories are thought to be helpful - that is why many children benefit from using ibuprofen during exacerbations and it is also why prednisone bursts are used. Unfortunately, the symptoms often return after the prednisone burst or return with the next infection.

 

If you are not using ibuprofen with your son, you may want to try adding that.

[momto2pandas]

I haven't read this whole thread (running out to see Eclipse!) but also don't forget that there is more to autoimmune disease than misdirected autoantibodies/molecular mimicry. Inflammatory cytokines, which can be influenced by things other than infections, also create their own set of psych symptoms. Just to give one example.

[Buster]

Such a great clear question and I don't have a great answer. This may be a good one to challenge the researchers with.

 

Let me split the question into one about other bacterial/viral infections and one about auto-feedback due to neuronal exposure.

 

In your reading you've probably run across the term super-antigens. The exotoxins of GABHS and Staph are the best characterized super-antigens, but any pathogenic microbes can produce super-antigens (for example, mycoplasma pneuomonia).

 

Super-antigens work by activating T-cells and recently appear to activate B-cells (http://www.springerlink.com/content/l40373ph04460474/) without any of the normal pattern matching that would activate only those antibodies for a particular antigen. This means stuff that shouldn't be getting activated is getting activated by some other trigger. I think this is explaining why mycoplasma pneumonia could be a subsequent trigger. I even wonder if this is what is happening in Lyme.

 

Now the other part of your question is much more tricky. If a T-cell finds neuronal tissue, will it activate a B-cell and create the 24.3.1 antibody. This makes sense to me but frankly I don't know. ADEM could easily be this situation (i.e., an activated B-cell that producing antibodies that actually signal destruction of neuronal tissue). In ADEM, they see the white patches on MRIs indicating demylination and so my gut says that ADEM is a BBB disruption that triggers antibodies that cause destruction of neuronal tissue.

 

I don't think this is the case in PANDAS because they don't see demyelination. In PANDAS, they don't see those white patches. By the way, that actually is good news. It's as if the antibodies are binding to the dopamine/tubulin receptors but not triggering phagocytosis (i.e., interference without causing macrophages engulfment or cell apoptosis).

 

This makes me think it is more a super-antigen recruitment of non-specific T-cells rather than a straight feedback cycle of an open BBB causing B-cells to trigger anti-neuronal antibodies.

 

I hope the above makes sense. I should stress that I don't think anyone knows. What's interesting in PANDAS is that it looks like binding is occuring but not destruction -- interference rather than demyelination.

 

Regards,

 

Buster

 

 

So, are you asking if the immune system will produce autoantibodies in the absence of strep, to the basal ganglia, because it mistakes something there as strep antigen? That's a great question!

 

Peg - yes - thank you - that is EXACTLY what I was trying to say! You are so articulate~!

Edited July 3, 2010 by Buster

[kimballot]

Thanks, Buster - as always you are a huge help! I was a little lost with ADEM - somehow I had not come across that before, but found it at http://my.clevelandclinic.org/disorders/ac...c_overview.aspx Good thing I never saw this before as I would have been bugging docs and trotting off to Cleveland Clinic for a diagnosis at some point over the past 13 years!

 

Sounds like - bottom line- we need to keep inflammation down in addition to reducing strep exposure.... Let us know if you come across anything on T Cell memory for 24.3.1

 

Thanks!