This study has me excited

[peglem]

This article is a study done in the autistic population, but it has to do with neuromodulation, and so I thought you all might find it interesting:

 

http://www.jneuroinflammation.com/content/4/1/3

 

and in looking up terminology to better understand, I came across this:

 

http://www.anapsid.org/cnd/diagnosis/cheneyis.html

 

which gave me some Aha's into the high/low titers issues.

 

Sure would like some feedback and discussion of these, if you get a chance.

[Pudgeo]

THANKS!! Awesome info for us PANDAS folks!! Sarah

[kim]

Peglem,

 

I have read the study a couple of times and could probably read it 5 more and get more questions each time!

 

I'm thinking that the ahh haa was the part about the body sort of burning out, with producing antibodies, hence low titers?

 

I thought Dnase detected something that the strep put off itself. I didn't look at ASO (used to know this stuff but I think I have forgotten more than I've retained!)

then I found these two statements, so I'm wondering which it is? I'm thinking the it's the "antibodies against." That was something that always confused me. I guess the first statement just leaves out the antibody part.

 

http://www.healthatoz.com/healthatoz/Atoz/...ibody_tests.jsp

Antideoxyribonuclease-B titer (anti-DNase B, or ADB)

 

Anti-DNase-B, or ADB, also detects antigens produced by group A strep, and is elevated in most patients with rheumatic fever and poststreptococcal glomerulonephritis.

 

http://cancerweb.ncl.ac.uk/cgi-bin/omd?anti-DNAse+B

 

anti-DNAse B

This is a serologic blood test used to detect antibodies against antideoxyribonuclease B (anti-DNAse , an antigen that is produced by group A streptococci

 

 

I also wanted to share an article written by Hilary Butler. I was fortunate enough to be reading a forum where she was actively posting a while back. It was a vaccine forum. I learned so much from her. Not only in relationship to vaccines, but nutrition, functioning of the immune system etc. This article has some really good discussion on the Th1 TH2 stuff that you might be interested in, not necessarily related to vaccination, just functioning.

 

http://www.whale.to/vaccines/butler.html

 

This is just an excerpt of a pretty long discussion:

 

The immune system has two “sides”. One is Th1, which is the usual response to diseases caught naturally. A healthy immune system has a “bias” towards Th1. Th2 is the “other” side, and people who have allergies, asthma and disease with an auto-immune origin have what is known as a Th2-skewed immune system. (New England J. Med 1992, Vol 326, No 5, 298-304 was one of the first references, now there are hundreds).

 

When a mother is pregnant, her pregnancy is controlled by cytokines, and requires a predominance of Th2 cytokines in order not to reject the baby. (Acta Paediatra 1997; 86: 916-918) A “Th1 driven” immune system would treat the baby as a graft, thereby miscarrying. Drugs are used to suppress the immune systems of transplant recipients for the same reason.

 

When a baby is born, it’s immune system is initially Th2-skewed, by virtue of the mother’s immune system. The mother’s immune system changes very quickly, and her breastmilk will help to change the baby’s balance, and will also “buffer” and assist in the development of the baby’s immune system.

 

The first years of life if the time when the “difference” between “vaccine” and “natural” immunity is so important, because most diseases promote a Th1 immunity. The portal of entry, and learning pathways teaches and matures the immune system, and helps in the prevention of both allergy-development and auto-immune disease. The “antigen” is processed, with the help of immunological factors in breastmilk and the baby’s cued-in immune system through the mucous membranes and the various “layers” of the immune system, producing an end-point called antibodies.

 

Some recent research which is as yet unpublished (I wonder who would have the guts to publish it) is looking at hundreds of mothers who have abnormally high level of antibodies to measles following vaccination. Their children, who became autistic after the MMR vaccine, are also found to have abnormally high levels of antibodies to Measles. The unsolved puzzles to this question are: Is there an inheritted immuno-dysfunction here? Did the high level of antibodies from the mothers cause the babies to have a catastrophic reaction to the MMR vaccine? What cytokine model are we looking at in the children?

 

The answer is that we don’t know, because no-one will research these issues. Not one vaccine company wants even the remote possibility of corporate suicide if the results show that vaccines do, as thought, damage the basic integrity of the immune system in some people.

 

 

I think Michelle was either using Actos for her son for a short period, or it was recommended and she declined. Maybe she will pop in with her experience. I know how frustrating it is to find/read info and not have anyone to discuss it with, but any part of this that you want to have a go at, I'm with ya!

[peglem]

Well, mostly I want to check that I understand the info correctly (especially from the 2nd site- the Cheney article) and extrapolate some implications from it. I drew the diagram that was described in the article. My daughter has low ASO and low antiDnase titers. also zero IgE. So does this mean her th2 side is not working? Or did the fact that she had untreated strep for so long shut it down? (years, I think) In either case, it would seem that her Th2 side is not responding very well. The article mostly talked about overactive Th2 side...But I think I'm dealing with the opposite.

 

The other thing I'm thinking is the Th2 side is the one that uses antibody producing cells to fight infection, so it would make sense that vaccines, in the sense that their objective is to stimulate antibody production, could easily trigger overactivity in the Th2 side, especially if you're vaccinating against multiple organisms at the same time.

 

I hope if Michelle, or anybody else out there has used Actos, they will chime in here with some feedback.

[peglem]

Oh, and where do the cytokines come from that trigger the Th0 cells to "pick sides"?

[kim]

Peglem,

 

In the absence of elevated titers, your thinking makes sense to me. I'm understanding it the same way you are.

 

This article looked interesting. This would suggest more of a TH1 involvement, I would think. In this scenario, could the TH2 response be suppressed (hence antibody production)? From the last sentence, I wonder what epitope that refers to?

 

http://neuro.psychiatryonline.org/cgi/content/full/16/3/252

 

Most recently, a prospective study provided convincing evidence establishing a temporal relationship between GABHS infections and PANDAS. In this study, authors proposed the role of GABHS-associated toxins in the development of pathophysiology of PANDAS instead of the role of traditional antibodies. GABHS-associated toxins act as superantigens within the host. By binding both the Class II major histocompatibility complex molecules on antigen presenting cells (HLA Class II) and specific Variable-ß regions on the T cell receptor, superantigens can undermine immune function. Allelic changes within the HLA Class II can lead to proliferation of specific T cell clones at a far higher orders of magnitude than what would be expected in the absence of superantigens. These expanded T cells interact not only with the M protein epitope but also cross-react with the epitope within the host tissues.

 

 

 

In regards to IgE, from the looks of this it appears both arms would be involved if you look at these statements. I'm assuming that your daughter doesn't appear to have inhaled type allergies?

 

 

TH1

Cellular Immunity

A branch of the immune system which involves direct attack by immune cells often called "T" cells. Antibodies play less of a role.

 

TH2

Humoral Immunity

This refers to immunity to infection created by proteins termed antibodies, often referred to as "B" cells.

 

http://www.gene.com/gene/products/educatio...nology/ige.html

 

IgE and the Allergic Cascade

In some people, allergen exposure can cause a reaction known as the allergic response. This occurs when allergens are inhaled into the respiratory tract (nose, throat and lungs) and attach to the mucous membranes. These allergens are seen by the immune system as foreign invaders and an immune response is produced as the body prepares to fight them off. During this response, T-cells (a cell type of the immune system) send a signal to B-cells (B-lymphocytes) and stimulate production of IgE antibodies — a key protein involved in the allergic cascade

[peglem]

Thanks for that article, Kim. So, its saying that maybe PANDAS is caused by toxins produced by strepA...but is it still autoimmune in that case? I mean are the toxins causing damage to the basal ganglia directly, or is the body producing antibodies to those toxins which are attacking the basal ganglia?

 

When we saw the immunologist to try to figure out why my daughter was not clearing the strep, even with antibiotics (it came right back) He did a challenge with pneumovax: He pulled baseline titers (to I think it was @14 strains of pneumonia causing bacteria), then vaccinated. The 1st time there was almost no response to the vaccine- just a few strains had antibodies slightly above baseline, but not considered a successful response. On repeating the vaccine, the titer response was normal. So, he said he had fixed the problem- demonstrated that her immune system was now responding. But, the strep was still chronic w/ only behavioral symptoms, no immune response (as in inflammation/fever), and no elevated strep titers. So the immunologist pronounced her a carrier. But, I kept thinking if she has the bacteria in her body-they're there and living, eating and excreting, so how could they be harmless? They give off neurotoxins and we had a very strong correlation between the +strep and neurological symptoms.

 

My daughter had many, many sinus problems when she was younger (when all her regression started)- nobody ever tested her for strep at that time. She was frequently not even given antibiotics for it. And since it seemed to be seasonal (on hindsight, I think it was correlated more to the school year than seasons) it was pronounced allergies. When she was finally tested for allergies years later- none showed up, not a thing. And while her tonsillectomy did not eradicate the strep like we had hoped, she almost never has sinus infections now (or maybe its the antibiotics?). So, that's my really long way of saying, no, she doesn't have inhaled allergies.

 

My daughter also has had yeast problems which should be a Th1 trigger. So does that mean her Th1 side is deficient as well?

 

Anyway, I don't want to try Actos just yet, but when more studies are done, I'll probably be toting them to her pediatrician, who will role his eyes (he loves me, really!) and try to figure out a way to justify prescribing it to a nondiabetic child.

[michele]

We did try to use Actos for awhile at our DAN's suggestion. He fully believes Actos will be used for autistic kids by mainstream Dr's in the next five years. I did stop it though because a lot of the people on the internet freaked me out about the long term consequences of its use on my sons health. I do know that the kids can get worse at first when they go on it. In my sons case his tics came out the worst during this time period. Possibly if I had stuck with it his immune issues would have improved though. I do realize now that my son does have alot of Asperger characteristics though and the Actos might have really helped him. Is it common that alot of PANDAS kids have autistic characteristics? Do you think that PANDAS/tourettes and aspergers overlap? How do you get a correct diagnosis? Do you think the treatments differ?

 

Michele

Peglem,

 

I have read the study a couple of times and could probably read it 5 more and get more questions each time!

 

I'm thinking that the ahh haa was the part about the body sort of burning out, with producing antibodies, hence low titers?

 

I thought Dnase detected something that the strep put off itself. I didn't look at ASO (used to know this stuff but I think I have forgotten more than I've retained!)

then I found these two statements, so I'm wondering which it is? I'm thinking the it's the "antibodies against." That was something that always confused me. I guess the first statement just leaves out the antibody part.

 

http://www.healthatoz.com/healthatoz/Atoz/...ibody_tests.jsp

Antideoxyribonuclease-B titer (anti-DNase B, or ADB)

 

Anti-DNase-B, or ADB, also detects antigens produced by group A strep, and is elevated in most patients with rheumatic fever and poststreptococcal glomerulonephritis.

 

http://cancerweb.ncl.ac.uk/cgi-bin/omd?anti-DNAse+B

 

anti-DNAse B

This is a serologic blood test used to detect antibodies against antideoxyribonuclease B (anti-DNAse , an antigen that is produced by group A streptococci

 

 

I also wanted to share an article written by Hilary Butler. I was fortunate enough to be reading a forum where she was actively posting a while back. It was a vaccine forum. I learned so much from her. Not only in relationship to vaccines, but nutrition, functioning of the immune system etc. This article has some really good discussion on the Th1 TH2 stuff that you might be interested in, not necessarily related to vaccination, just functioning.

 

http://www.whale.to/vaccines/butler.html

 

This is just an excerpt of a pretty long discussion:

 

The immune system has two “sides”. One is Th1, which is the usual response to diseases caught naturally. A healthy immune system has a “bias” towards Th1. Th2 is the “other” side, and people who have allergies, asthma and disease with an auto-immune origin have what is known as a Th2-skewed immune system. (New England J. Med 1992, Vol 326, No 5, 298-304 was one of the first references, now there are hundreds).

 

When a mother is pregnant, her pregnancy is controlled by cytokines, and requires a predominance of Th2 cytokines in order not to reject the baby. (Acta Paediatra 1997; 86: 916-918) A “Th1 driven” immune system would treat the baby as a graft, thereby miscarrying. Drugs are used to suppress the immune systems of transplant recipients for the same reason.

 

When a baby is born, it’s immune system is initially Th2-skewed, by virtue of the mother’s immune system. The mother’s immune system changes very quickly, and her breastmilk will help to change the baby’s balance, and will also “buffer” and assist in the development of the baby’s immune system.

 

The first years of life if the time when the “difference” between “vaccine” and “natural” immunity is so important, because most diseases promote a Th1 immunity. The portal of entry, and learning pathways teaches and matures the immune system, and helps in the prevention of both allergy-development and auto-immune disease. The “antigen” is processed, with the help of immunological factors in breastmilk and the baby’s cued-in immune system through the mucous membranes and the various “layers” of the immune system, producing an end-point called antibodies.

 

Some recent research which is as yet unpublished (I wonder who would have the guts to publish it) is looking at hundreds of mothers who have abnormally high level of antibodies to measles following vaccination. Their children, who became autistic after the MMR vaccine, are also found to have abnormally high levels of antibodies to Measles. The unsolved puzzles to this question are: Is there an inheritted immuno-dysfunction here? Did the high level of antibodies from the mothers cause the babies to have a catastrophic reaction to the MMR vaccine? What cytokine model are we looking at in the children?

 

The answer is that we don’t know, because no-one will research these issues. Not one vaccine company wants even the remote possibility of corporate suicide if the results show that vaccines do, as thought, damage the basic integrity of the immune system in some people.

 

 

I think Michelle was either using Actos for her son for a short period, or it was recommended and she declined. Maybe she will pop in with her experience. I know how frustrating it is to find/read info and not have anyone to discuss it with, but any part of this that you want to have a go at, I'm with ya!

[peglem]

We did try to use Actos for awhile at our DAN's suggestion. He fully believes Actos will be used for autistic kids by mainstream Dr's in the next five years. I did stop it though because a lot of the people on the internet freaked me out about the long term consequences of its use on my sons health. I do know that the kids can get worse at first when they go on it. In my sons case his tics came out the worst during this time period. Possibly if I had stuck with it his immune issues would have improved though. I do realize now that my son does have alot of Asperger characteristics though and the Actos might have really helped him. Is it common that alot of PANDAS kids have autistic characteristics? Do you think that PANDAS/tourettes and aspergers overlap? How do you get a correct diagnosis? Do you think the treatments differ?

 

Thank you so much for responding! My daughter is considered severely autistic- makes it really difficult to get doctors to look at medical issues because so many can't see past the autism. I think a lot of autistic kids have obsessive compulsive behaviors, many have abnormal movements and loads of anxiety. Also, gut problems are prevalent in autism and the reasearch seems to show immune system involement. Some people think a child can become autistic as a result of PANDAS. There does seem to be some overlap. I have to tell you, that I think autism/aspergers are worthless dx's. They are based solely on how the diagnostic clinician interprets outward behaviors. It has qualified my daughter for state medical assistance and special education (although it really doesn't seem all that special to me!- or educational for that matter!) I know a lot of people say "right diagnosis, right treatment." In my experience nobody really knows the right treatment for autism (well, I can think of an exception to that- in a minute) and the range of behaviors and impairment are so vast- even those who are considered "professionals" in the field have very little idea what to do to correct it. They tend to build a world where the child will be comfortable and unchallenged instead of teaching them to deal with the real world. So, treatments may differ, but will they be effective? I dunno. I used to be very optimistic about this...but, the more I deal with it, the more I realize her teachers just don't know what to do about it all. I don't know what to do about it, either, but I never persued or been given a degree in special education. They're paid and trained to be experts. If you need an aspergers dx to obtain services for your child- go for it, otherwise, I don't really think the label is helpful. That's just my opinion-

 

Anyway, the only program I know of that actually treats the autism- that is, corrects the characteristics that make a person autistic (5 core deficits) is Relationship Development Intervention. It evaluates clients' social/emotional development, determines what they need and have methods for developing the neurology to correct the deficits. This program is about bringing about normal social/emotional development that has, for whatever reason not occured typically, so I don't see why it would have to be just for autistic people. For instance one of the things they work on is regulating attention and setting priorities on what is attended to. This is something ADD kids have trouble with, even if they aren't autistic.

 

If you're interested this is the site: www.rdiconnect.com

 

I'm wondering about your experience with Actos- how long was your son on it? Is it typical for kids to get worse before better? Or is that one of those sometimes things, where you're being urged to stick it out? My concern is that they are unable to pinpoint what's going on inside my child well enough to know whether this treatment makes sense for her. For sure though, if it made her worse and they couldn't explain why, or how it would improve, she'd be off it.

[kim]

Peglem/Michelle,

 

So glad you guys are able to discuss this. Michelle, you said "tics were worse while on Actos." Did you see improvement in any other area? Can you say how long Andrew was on it?

 

 

Peg,

 

Thanks for that article, Kim. So, its saying that maybe PANDAS is caused by toxins produced by strepA...but is it still autoimmune in that case? I mean are the toxins causing damage to the basal ganglia directly, or is the body producing antibodies to those toxins which are attacking the basal ganglia

Your very welcome. This is just the way I'm interputing this and I'm sure no expert here, but it looks like a direct attack by a form of T cell has been suspected in past studies. Yes, something in the strep bacteria is causing an autoimmune attack, but not by antibodies.

 

Here is one talking about rheumatic fever, but makes this point (I think). This study is dated 1995, so I'm sure there is more current research but I was looking for something to sort of confirm that a TH1 response could be responsible for a reaction. The first part talks about the normal antibody attack, then it goes into this....

 

bolding mine

http://www.circ.ahajournals.org/cgi/content/full/92/3/281

 

While there is a vast amount of evidence implicating cross reactions between streptococcal antigens and relevant mammalian antigens at a humoral level, only recently has the question of the cellular response to these cross reactive antigens been addressed. Using peripheral blood mononuclear cell populations obtained from acute rheumatic fever patients. Read and co-workers11 12 and others13 demonstrated that there was a heightened cellular response to both streptococcal and mammalian antigens in these patients compared to controls and patients with poststreptococcal glomerulonephritis. The streptococcal cellular reactivity persisted for at least 2 years after the initial attack. Most interesting was the observation that this cellular reactivity was primarily directed to membrane antigens from rheumatic fever associated strains.11

 

Perhaps most relevant to the disease process has been the studies of the cell types in the cardiac lesions themselves. Raizada et al14 clearly demonstrated the presence of T-cell subsets in a series of valves removed 10 to 20 years after the attack. Kemeny and colleagues15 carried out a more extensive study of the cell types found in the valvular specimens some of which were obtained during acute rheumatic fever carditis. In these valves, approximately 50% of the cells were macrophages and the CD4 to CD8 ratios approached 4:1. The preponderance of CD4 cells in the lesions strongly supports a hypercellular/cytotoxic reaction to streptococcal and/or cross reactive mammalian antigens. Yoshinaga showed that T-cell lines derived from these same valvular specimens and primed with streptococcal membrane antigens reacted to cell walls and membranes of rheumatic fever associated strains. Surprisingly, no reactivity to M protein or cytoskeletal proteins was seen in their studies

AND

 

What is true is that the cellular arm of the immune system appears to more initimately involved in the disease process than previously recognized. The authors have clearly opened up a path for what will be an area of future fruitful investigations.

 

 

Also, the challenge with the vaccine was interesting. I'm wondering if that vax contained aluminum (which is notorious for prompting a TH2 response). I found a study where children with nephrotic syndrome were given a 23-valent pneumococcal polysaccharide vaccine. At 4 weeks, if there was a twofold increase in the antibody titers, the children were considered "antibody responders." I'm wondering, in light of your daughters non response to the first vaccine, if the immunologist had any thoughts. The idea that he "fixed" a problem with the immune system with a double dose of an aluminum spiked vaccine (if indeed it contained alum) seems a bit bizarre to me. So he was able to achieve what is considered an acceptable antibody response using 13 weakened strains of pneumonnia and an adjuvant, twice. Why didn't he focus more on her response that was outside of the norm to the first injection and see what knowledge could be gleened from that? If vaccines were going to fix a genetic preexisting deficit in the TH2 arm of the immune system, I'm sure they would have accomplished that with her childhood vaccines (assuming she had all of them). Sorry for the negative undertone, it's just frustration. Maybe you have some other thoughts on the results. This is the study I was referring to

 

http://www.advmolmed.com/issue/20074/fulltext/txt_03.asp

[peglem]

The vaccine did not contain aluminum- I checked it out before agreeing to do this test. This whole process really confused me, because I was puzzled by the lack of concern when the 1st vaccine did not provoke a response. Then when the second did provoke a response, I was mystified when she was pronounced fixed. I think the reasoning may have been that they stimulated the TH2 side and got it responding...so now it works. As far as testing vaccine titers, the only one I saw on the lab sheet was tetanus, which tested "protective". It was thought(by the immunologist) that from this point foward her body would fight the strep. It did not.

 

I began suspecting that my daughter's case was not autoimmune, because if you aren't producing antibodies very well, then what is attacking the body's own tissue. I thought autoimmune disease was when the immune system produced antibodies to self tissue. I suppose, though, something could be "marking" body tissues with non self antigens- triggering NK cells to attack. I guess I need to find out how the strep neurotoxins work. Or maybe I don't- what good would it do me, really? I mean, the azith is keeping the strep at bay, and I don't know how that info would help as far as treatment.

 

On carrier state- I suspect that biofilms are involved in this.

 

Thanks again, for doing my research for me- I agree that this does indicate a Th1 reaction to strep causing tissue damage.

[Buster]

Oh, and where do the cytokines come from that trigger the Th0 cells to "pick sides"?

 

Hi Peglem,

 

Fascinating article!

 

In answer to your question, it seems that the cytokines are generated by B cells, Macrophages, and Dendrite cells. My understanding is that B cells and Macrophages can only activate Memory T-cells (i.e., ones that have already seen the presented antigen signature). Dendrites can activate memory T-cells and naive T-cells (i.e., those that could go either to Th1 or to Th2). So the dendrites seem to be the deciders of whether to send IL-10 or IL-12 to cause the naive T-cell to go to Th1 or Th2.

 

You might want to look at http://en.wikipedia.org/wiki/T-helper_cell .

 

What I found particularly interesting (with respect to PANDAS) was that multiple articles indicate that GABHS produces super-antigens that bind directly with the naive T-cells and thus cut the Dentrite and Macrophages out of the whole process. In one of the studies I was reading it indicated that Th2 (the inflammatory response) was being created even though there wasn't any IL-10 (i.e., that the super antigen was itself causing the production of Th2).

 

So this got me thinking -- yeah, I know I'm out on a limb here, but see what you think. Suppose that the super-antigens are converting naive Th0-cells into Th2 but miscoding them --> causing inflamation, but also creating cells that aren't looking for things the macrophanges want them to find. Instead this super-antigen is causing the creation of Th2 cells that will destroy any Th1 or Th2 cells that would have attacked the actual strep. I know this sounds odd, but why else would the SuperAntigen attach directly to the naive Th0 cells?

 

So now we bring azithromycin into the mix (or progesterone or NSAIDs or aktos or ...) and we get something that is slowing up the production of Th2 cells and rebiasing toward Th1 production. So if the strep were intracellular than the Th1 cells can now get it and not be killed off by these mis-programmed Th2.

 

Anyway, just a theory, but wow! great paper.

 

Regards,

 

Buster

[Buster]

Hi Peglem,

 

I really appreciate you bringing up this very interesting set of questions and the paper.

 

I suppose, though, something could be "marking" body tissues with non self antigens- triggering NK cells to attack. I guess I need to find out how the strep neurotoxins work. Or maybe I don't- what good would it do me, really? I mean, the azith is keeping the strep at bay, and I don't know how that info would help as far as treatment.

 

On carrier state- I suspect that biofilms are involved in this.

 

Thanks again, for doing my research for me- I agree that this does indicate a Th1 reaction to strep causing tissue damage.

 

I ran across the following link:

Encephalomyelitis-associated antimyelin autoreactivity induced by streptococcal exotoxins

According to http://www.neurology.org/cgi/content/abstract/54/7/1433

 

CONCLUSION: In vivo exposure to S. pyogenes may have induced activation of pathogenic myelin reactive T cells, contributing to the dramatic inflammatory demyelination.

 

This certainly seems to support the hypothesis that the super antigens interaction with the Th0 cells is having a significant affect on the creation of the T-cells/Th2 cells and that these created Th2 cells are attacking things other than what the dendrites or macrophages would have signaled.

 

On your other topic of the carrier state, I've been wondering whether the situation is that the colony isn't growing fast (i.e., isn't sensitive to penicillan's attack mechanism). Perhaps in the carrier state, the bacteria is just slow growing -- and thus the amount of Streptolyicin O/Dnase-B is low or controlled.

 

Kaplan provided an alternate explanation (and a bunch of questions) in his 2006 paper "Reduced Ability of Penicillin to Eradicate Ingested Group A Streptococci from Epithelial Cells: Clinical and Pathogenetic Implications"

 

http://www.journals.uchicago.edu/doi/abs/10.1086/508773

 

Here he notes that GABHS is going intracellular.

 

Perhaps what is happening in the carrier state is that the GABHS is recolonizing after cell breach, invading other cells similar to a virus, and then the extracellular bacteria is getting destroyed again by anti-biotics during rapid growth.

 

Perhaps what azithromycin is doing in this case is :

1) as an antibiotic, it is going intracellular and preventing the protein growth and thus preventing the cell from "bursting" -- biostatic

2) as an immunomodulator is re-biasing the activated Th2's back to Th1's -- i.e., creating more antibodies to go after the intracellular strep.

 

I sure wish I knew more here but think this whole line of thought is promising and would be interested in anything others find here.

 

Regards,

 

Buster

[michele]

We tried the Actos from July until September. When I went to see Dr. Murphy she recommended we stop the Actos immediately. That its risks outweighed its proven benefits. He was ticcing much worse by then. It was constant cracking finger and toe knuckles. He was doing knee bends and touching the ground. I was doing the GF CF diet also. I then started him on the daily Augmentin 250 mg prophylaxis and fish oils and probiotics. I just didn't see the benefits from the Actos. I did use the Monolaurin for awhile which also is used to help with immune issues. Thanks for the autism info. I will look into it further.

 

Michele

We did try to use Actos for awhile at our DAN's suggestion. He fully believes Actos will be used for autistic kids by mainstream Dr's in the next five years. I did stop it though because a lot of the people on the internet freaked me out about the long term consequences of its use on my sons health. I do know that the kids can get worse at first when they go on it. In my sons case his tics came out the worst during this time period. Possibly if I had stuck with it his immune issues would have improved though. I do realize now that my son does have alot of Asperger characteristics though and the Actos might have really helped him. Is it common that alot of PANDAS kids have autistic characteristics? Do you think that PANDAS/tourettes and aspergers overlap? How do you get a correct diagnosis? Do you think the treatments differ?

 

Thank you so much for responding! My daughter is considered severely autistic- makes it really difficult to get doctors to look at medical issues because so many can't see past the autism. I think a lot of autistic kids have obsessive compulsive behaviors, many have abnormal movements and loads of anxiety. Also, gut problems are prevalent in autism and the reasearch seems to show immune system involement. Some people think a child can become autistic as a result of PANDAS. There does seem to be some overlap. I have to tell you, that I think autism/aspergers are worthless dx's. They are based solely on how the diagnostic clinician interprets outward behaviors. It has qualified my daughter for state medical assistance and special education (although it really doesn't seem all that special to me!- or educational for that matter!) I know a lot of people say "right diagnosis, right treatment." In my experience nobody really knows the right treatment for autism (well, I can think of an exception to that- in a minute) and the range of behaviors and impairment are so vast- even those who are considered "professionals" in the field have very little idea what to do to correct it. They tend to build a world where the child will be comfortable and unchallenged instead of teaching them to deal with the real world. So, treatments may differ, but will they be effective? I dunno. I used to be very optimistic about this...but, the more I deal with it, the more I realize her teachers just don't know what to do about it all. I don't know what to do about it, either, but I never persued or been given a degree in special education. They're paid and trained to be experts. If you need an aspergers dx to obtain services for your child- go for it, otherwise, I don't really think the label is helpful. That's just my opinion-

 

Anyway, the only program I know of that actually treats the autism- that is, corrects the characteristics that make a person autistic (5 core deficits) is Relationship Development Intervention. It evaluates clients' social/emotional development, determines what they need and have methods for developing the neurology to correct the deficits. This program is about bringing about normal social/emotional development that has, for whatever reason not occured typically, so I don't see why it would have to be just for autistic people. For instance one of the things they work on is regulating attention and setting priorities on what is attended to. This is something ADD kids have trouble with, even if they aren't autistic.

 

If you're interested this is the site: www.rdiconnect.com

 

I'm wondering about your experience with Actos- how long was your son on it? Is it typical for kids to get worse before better? Or is that one of those sometimes things, where you're being urged to stick it out? My concern is that they are unable to pinpoint what's going on inside my child well enough to know whether this treatment makes sense for her. For sure though, if it made her worse and they couldn't explain why, or how it would improve, she'd be off it.

[kim]

We tried the Actos from July until September. When I went to see Dr. Murphy she recommended we stop the Actos immediately. That its risks outweighed its proven benefits. He was ticcing much worse by then.

Michelle, if you look at the Actos study it doesn't look like they really know the mechanism by which it may help. I haven't read it again since Peglem first posted it, but I think they were hoping that it would tamp down TH2. Then it says one small study appeared to boost it? Maybe it was having the wrong effect with your son.

 

Something else I'm wondering about (maybe peg or buster have a thought here) Look at this study regarding strep and RA, which I thought you would be interested in. Does this mean that it will only be certain strep bacteria that express these M proteins that will cause the autoimmune reaction? Could you "have strep," but not see any increase in problems, if the strep doesn't have the M protein that an individual has a problem with?

 

http://www.jimmunol.org/cgi/content/abstract/146/9/3132

 

Epitopes of group A streptococcal M protein shared with antigens of articular cartilage and synovium

RW Baird, MS Bronze, W Kraus, HR Hill, LG Veasey and JB Dale

Department of Veterans Affairs Medical Center, Memphis, TN 38104.

 

Rabbit antisera evoked by purified pepsin-extracted group A streptococcal M proteins were screened for the presence of joint cross- reactive antibodies by indirect immunofluorescence using thin sections of mouse knee joints. Pep M1, M5, and M18 antisera contained antibodies that cross-reacted with chondrocytes, cartilage, and synovium. Immunofluorescence inhibition assays showed that some of the joint cross-reactive epitopes were shared among the three heterologous serotypes of M protein. The pep M5 joint cross-reactive epitopes were localized to three different synthetic peptides of the C-terminal region of pep M5. Immunoblot analyses showed that the M5 joint cross- reactive antibodies recognized two proteins of human synovium and cartilage of molecular mass 56 and 58 kDa. The cross-reactive antibodies binding to the 56-kDa protein were inhibited by purified vimentin in immunoblot inhibition experiments. M protein-specific antibodies from patients with acute rheumatic fever were also shown to cross-react with joint tissue in a pattern similar to the rabbit antisera. Rabbit and human M protein-specific antibodies that were bound to articular cartilage activated significant levels of complement when compared to control serum, suggesting that M protein joint cross- reactive antibodies could potentially be involved in the pathogenesis of ARF and arthritis.

 

 

I haven't been abe to get my mind around the fact that they found nothing in these 12 children, but IF it's only a certain strep for a certain child that causes a problem, would they catch it using only 12 kids over 2 years? I wonder how many confirmed strep infections each child had during the 2 year period.

 

I'm also wondering about this statement. How did they determine this without a specimen of the brain tissue, which would be pretty hard to obtain from living subjects. I know there must be a logical answer to that question. I wonder if the actual study is available yet?

 

Moreover, researchers found no evidence of strep antibodies – the antibodies produced by the immune system against the streptococcus bacterium – binding to or interacting with brain tissue, a finding that makes an immune origin of PANDAS unlikely, investigators say.

 

 

http://www.hopkinschildrens.org/newsDetail.aspx?id=4914

 

June 04, 2008

A small but revealing study from Johns Hopkins Children’s Center challenges a controversial theory that strep infections cause a neuropsychiatric disorder in children marked by tics, jerking movements and obsessive-compulsive behaviors. The findings appear in the June issue of Pediatrics.

 

Working from the hypothesis that an overactive immune system in the wake of a strep infection mistakenly attacks a child’s brain and causes neuropsychiatric symptoms, researchers followed for two years 12 children diagnosed with PANDAS, (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections), but found no changes in the levels of immune proteins, the classic markers of autoimmune inflammation, during symptom exacerbation. Moreover, researchers found no evidence of strep antibodies – the antibodies produced by the immune system against the streptococcus bacterium – binding to or interacting with brain tissue, a finding that makes an immune origin of PANDAS unlikely, investigators say.