EndoS from strep pyogenes

[sf_mom]

So, I am making a little headway. I've sent the case history to a couple of strep experts.... One individual studied the outbreaks in Utah, one was at Harvard/Yale and one was Dr. Kaplan. I have peaked Dr. Kaplan's interest and he did mention 'That there is an illness causing these symptoms cannot be denied'. He found the connection fascinating and wants me to document a little more specifically for future reference. I am in the process of drafting some questions and I don't want them to be specifically 'just about my kids'. I hope to discuss the S Pyogenes exotoxin found by the Japanese in Kawasaki's.... He did say it is possible that it is PANDAS, PAND or both or neither. I hope to talk to him again in the near future. He did re-read Madeleine's paper based on the fact that all the kids have measurable CaM Kinase. Again, I think the 4th boy at playdate is also PANDAS.... he has all the symptoms but still needs to be tested in January. I haven't heard from the others strep individuals yet but hope to and will keep trying.

 

Feel free to forward any questions you may have and I'll ask them.

 

-Wendy

[sf_mom]

Buster/Kim: My father-in-law is a Urologist, while visiting for the holidays and discussing PANDAs he had the opportunity to read the following articles. He summarizes he thoughts on all three articles below.

 

 

1. Probable role of Streptococcus Pyogenes in Kawasaki Disease http://www.springerlink.com/content/l34qj830548q4q46/ (you have already read this article)

 

2. Effect of SpeB and EndoS from Streptococcus Pyogenes on Human Immunoglobulins http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/

 

3. Antibody-Mediated Neuronal Cell Signaling in Behavior and Movement Disorders http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf

 

 

--------------

 

 

In PANDAS when exposed to strep pyogenes early in life the humoral (antibody) portion of the immune response does not occur in affected children. The strep pyogenes antigens are not bound by the antibodies when infection occurs because PANDAS patients cannot produce the antibody due to AGE/state of immune system at time of exposure. Since this initial immunity to strep pyogenes infection is absent, the strep enters the PANDAS host and proliferates. This humoral response to the exposure to strep pyogenes is because it secretes protease enzymes that destroys antibodies measured by an ASO titers or Igg level.

 

This results in a 2nd immune response to components (polysaccharides) of the bacteria's cell walls producing an antibody (AB'). This second antibody cross reacts (also attacks) with nerve cell surfaces (brain) causing signaling activity (TICS, Chorea). Hence no raised titers unless additional exposures to more traditional strep strains occur.

 

 

Treating with IGG binds with and lowers the levels of (AB') in conjunction with antibiotics (protects child from continued exposure) eventually cures child.

 

--------------

 

THE HIGHER DOSE OF Antibiotics works because there is an underlying infection still within host!!!!!!!!!!! Relapses after PEX are because the bacteria was not fully eradicated. IVIG and antibiotics work because you overwhelm the bacteria. Some kids will need more than one treatment to recover and jump start their own immune system.

 

 

-Wendy

[momto2pandas]

Very interesting, Wendy. Thanks to you and to your father-in-law.

 

What is his explanation for/interpretation of the waxing and waning course? Is it that when additional exposures to more traditional strep strains occur, this activates the second antibody (don't really understand this part - why would there be insufficient immune response for an initial humoral reaction, but sufficient immune response for a secondary one - is the idea that this occurs at a later time during development? Is he saying that there is no IgM response, just an IgG response?) Presumably components of the cell walls are conserved across Strep strains, hence the ability for other strains to reactivate the immune response?

 

This also suggests that it should be possible to culture S. Pyogenes from somewhere in the host, as long as the infection has not been eradicated.

 

What about maternal immunity? Would breastfed babies not be expected to have some maternal immunity, at least assuming that they had their own immune response? There are many studies showing that breastfed babies are less likely to have childhood psychiatric disorders, which would be consistent with this idea. (Both of mine were breastfed - however, I have a primary immune deficiency, so maybe it didn't help...).

 

I would be very curious about your father-in-law's take on this as a urologist: does he think that the frequent urination and lower abdominal pain seen in many (most?) PANDADS kids during flares is consistent with (autoimmune) interstitial cystitis?

 

 

 

 

Buster/Kim: My father-in-law is a Urologist, while visiting for the holidays and discussing PANDAs he had the opportunity to read the following articles. He summarizes he thoughts on all three articles below.

 

 

1. Probable role of Streptococcus Pyogenes in Kawasaki Disease http://www.springerlink.com/content/l34qj830548q4q46/ (you have already read this article)

 

2. Effect of SpeB and EndoS from Streptococcus Pyogenes on Human Immunoglobulins http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/

 

3. Antibody-Mediated Neuronal Cell Signaling in Behavior and Movement Disorders http://www.pandasnetwork.org/CunninghamJNICaMKinase.pdf

 

 

--------------

 

 

In PANDAS when exposed to strep pyogenes early in life the humoral (antibody) portion of the immune response does not occur in affected children. The strep pyogenes antigens are not bound by the antibodies when infection occurs because PANDAS patients cannot produce the antibody due to AGE/state of immune system at time of exposure. Since this initial immunity to strep pyogenes infection is absent, the strep enters the PANDAS host and proliferates.

 

This results in a 2nd immune response to components (polysaccharides) of the bacteria's cell walls producing an antibody (AB'). This second antibody cross reacts (also attacks) with nerve cell surfaces (brain) causing signaling activity (TICS, Chorea). Hence no raised titers unless additional exposures to more traditional strep strains occur.

 

Treating with IGG binds with and lowers the levels of (AB') in conjunction with antibiotics (protects child from continued exposure) eventually cures child.

 

--------------

 

THE HIGHER DOSE OF Antibiotics works because there is an underlying infection still within host!!!!!!!!!!! Relapses after PEX are because the bacteria was not fully eradicated. IVIG and antibiotics work because you overwhelm the bacteria. Some kids will need more than one treatment to recover and jump start their own immune system.

 

 

-Wendy

[sf_mom]

The reason there is not detectable humoral response to the exposure to the strep pyogenes is because it secretes protease enzymes that destroys the antibodies measured by an ASO titers or IGG level.

 

Flair ups occur because of additional exposures, inadequate cross immunity and bacteria not being fully eradicated.

 

It would be difficult to find exactly where strep resides within host.

 

He does agree there would be maternal immunity but child would still have a potential vulnerability until age five when immune system is fully in place.

 

He does not believe urinary problems are due interstitial cystitis. Not sure of cause.

 

 

 

 

 

Very interesting, Wendy. Thanks to you and to your father-in-law.

 

What is his explanation for/interpretation of the waxing and waning course? Is it that when additional exposures to more traditional strep strains occur, this activates the second antibody (don't really understand this part - why would there be insufficient immune response for an initial humoral reaction, but sufficient immune response for a secondary one - is the idea that this occurs at a later time during development? Is he saying that there is no IgM response, just an IgG response?) Presumably components of the cell walls are conserved across Strep strains, hence the ability for other strains to reactivate the immune response?

 

Additional exposures and inadequate cross immunity. Never fully eradicated

 

This also suggests that it should be possible to culture S. Pyogenes from somewhere in the host, as long as the infection has not been eradicated.

 

What about maternal immunity? Would breastfed babies not be expected to have some maternal immunity, at least assuming that they had their own immune response? There are many studies showing that breastfed babies are less likely to have childhood psychiatric disorders, which would be consistent with this idea. (Both of mine were breastfed - however, I have a primary immune deficiency, so maybe it didn't help...).

 

I would be very curious about your father-in-law's take on this as a urologist: does he think that the frequent urination and lower abdominal pain seen in many (most?) PANDADS kids during flares is consistent with (autoimmune) interstitial cystitis?

[momto2pandas]

Thanks, Wendy. If it's not too much of a bother, could you tell me what about the PANDAS urinary issues he thinks would be inconsistent with interstitial cystitis? Just curious because there seems to be a correlation between other pediatric-onset anxiety/mood disorders and IC in some clusters. I know very little about urology so don't really know what the difference would be between IC and what we see in PANDAS. I'd love to understand it better.

 

 

The reason there is not detectable humoral response to the exposure to the strep pyogenes is because it secretes protease enzymes that destroys the antibodies measured by an ASO titers or IGG level.

 

Flair ups occur because of additional exposures, inadequate cross immunity and bacteria not being fully eradicated.

 

It would be difficult to find exactly where strep resides within host.

 

He does agree there would be maternal immunity but child would still have a potential vulnerability until age five when immune system is fully in place.

 

He does not believe urinary problems are due interstitial cystitis. Not sure of cause.

 

 

 

 

 

Very interesting, Wendy. Thanks to you and to your father-in-law.

 

What is his explanation for/interpretation of the waxing and waning course? Is it that when additional exposures to more traditional strep strains occur, this activates the second antibody (don't really understand this part - why would there be insufficient immune response for an initial humoral reaction, but sufficient immune response for a secondary one - is the idea that this occurs at a later time during development? Is he saying that there is no IgM response, just an IgG response?) Presumably components of the cell walls are conserved across Strep strains, hence the ability for other strains to reactivate the immune response?

 

Additional exposures and inadequate cross immunity. Never fully eradicated

 

This also suggests that it should be possible to culture S. Pyogenes from somewhere in the host, as long as the infection has not been eradicated.

 

What about maternal immunity? Would breastfed babies not be expected to have some maternal immunity, at least assuming that they had their own immune response? There are many studies showing that breastfed babies are less likely to have childhood psychiatric disorders, which would be consistent with this idea. (Both of mine were breastfed - however, I have a primary immune deficiency, so maybe it didn't help...).

 

I would be very curious about your father-in-law's take on this as a urologist: does he think that the frequent urination and lower abdominal pain seen in many (most?) PANDADS kids during flares is consistent with (autoimmune) interstitial cystitis?

[sf_mom]

IC typically happens in older individuals, college age and up. For some reason, people who develop IC don't form an inter layer to their bladder, was my interpretation of 'what he said'. He is not familiar with urinary issues associated with PANDAS so it would be difficult for him to speculate other then they are directly impacted by bacteria which when resolved should help the urinary issue.

 

-Wendy

[momofgirls]

Wendy

That is all very interesting and I've read through it a few times to try and really grasp the concept! Let me make sure I understand...strep titers are not elevated because the protease enzyme destroys the antibodies tested?

What do you think about viruses and flares? Are you thinking that once the strep is REALLY gone that viruses will not cause flares?

Kim

[sf_mom]

Wendy

That is all very interesting and I've read through it a few times to try and really grasp the concept! Let me make sure I understand...strep titers are not elevated because the protease enzyme destroys the antibodies tested?

What do you think about viruses and flares? Are you thinking that once the strep is REALLY gone that viruses will not cause flares?

Kim

 

 

Kim, my father-in-law basically drew me a graph and once the child's body hits the cross over point with their immune system they will not have episodes not even to the S Pyogenes if enough antibodies to other strains exist.

 

-Wendy

[momto2pandas]

That must presume a normally active immune system, no? If one has an immune deficiency in which one fails to produce a proper immune response in the first place or in which one fails to retain immune memory, things would be different, no? Then "enough antiboides to other strains" will never happen.

 

There are certainly adults who have episodes, still, despite tons of strep infections. I can think of a couple who have been in their 70's and 80's. But not 100% immunocompetent.

 

 

Wendy

That is all very interesting and I've read through it a few times to try and really grasp the concept! Let me make sure I understand...strep titers are not elevated because the protease enzyme destroys the antibodies tested?

What do you think about viruses and flares? Are you thinking that once the strep is REALLY gone that viruses will not cause flares?

Kim

 

 

Kim, my father-in-law basically drew me a graph and once the child's body hits the cross over point with their immune system they will not have episodes not even to the S Pyogenes if enough antibodies to other strains exist.

 

-Wendy

[sf_mom]

Correct, hopefully IVIG would take care of any immune deficiencies as a result of bacteria...... This perspective only takes into account age of immune system development. In this situation, it is very clear it is NOT a predisposition, although in some cases that might exist....

 

-Wendy

[momofgirls]

Thanks to you and your father in-law Wendy. I am going to forward those articles to Dr. Bouboulis. This research is very important for doctors treating PANDAS.

[sf_mom]

Definitely forward and include my summary comments from him as its important for each Dr. to make the connection correctly between the three articles.