Going to IVIG in 2 weeks despite very mild PANDAS

[momto2pandas]

Can't believe it, but it looks like my kids will be getting IVIG in three weeks, pending repeat bloodwork. Based on their immune results (below normal range) and history of recurrent/chronic infections, plus PANDAS (and lots of other autommune stuff in ds6), Dr. B feels that there is no reason to wait. I can't get used to the idea. Particularly for ds3, his PANDAS is so mild that I can't even say that I'm absolutely 100% sure about it, and even ds6 is pretty well off as far as PANDAS cases go. Even their infections - though persistent and recurrent - have never caused hospitalization or even much time out of school. Dr. B feels that we should go ahead BEFORE they get sicker, and I guess it makes sense given the labs, but somehow I always thought IVIG was VERY far in the future if things progressed a LOT, and I feel strange about it in kids that basically seem quite normal and healthy. I keep switching between feeling haunted by the thought that we're being too "experimental" on the kids -- and feeling grateful that maybe they're actually going to get "fixed" before they get "broken" in any way that will leave real scars (what a contrast to my own childhood...). People like my Mom keep questioning whether it's really necessary (funny that it's she, of all people, given that she experienced what happened in my untreated childhood!), and I watch the kids playing happily with friends, doing well in school, and looking pretty healthy, and it's hard not to feel like I'm a nut for taking them for IVIG.

 

Does anyone know if PANDAS in immune deficiency ever gets better withOUT IVIG? Or if immune deficiency ever gets better on its own withOUT IVIG? I keep worrying about the risks of treating, but my husband argues that there is more risk in NOT treating... I just wish that I KNEW that that was the case.

 

We're getting CamKinase on them and hope to have the results before proceeding. I think if I see in black and white that their CamK's look PANDAS (and I'm quite sure that they will), I will feel somewhat better about the whole thing.

 

Luckily Dr. B expects insurance to pay so at least financial issues don't weigh in much one way or another.

 

Guess I'm just looking to vent.... and it's all too much to explain to my "real life" friends.

[Stephanie2]

First, have you tried any supplements to help enhance their immune systems? We see a DAN doctor and my 5 year old's immune system is much better now (he used to get sinus, chest, ear infections with every cold, he used to have asthma, allergies). He still has PANDAS, though. My 2 year old is better, too, but we have not done as much with the DAN protocol with him yet, so I expect to see even further improvements in him too.

 

Also, I wanted to say that my 5 year old had his first IVIG yesterday. It took 6 months for my husband and I to come around to this decision. Now that it is over with, I am wondering what I was so worried about (although, I guess the hard part could be ahead of me b/c I have not seen the side effects quite yet). It was really no big deal and I am glad I did it. However, it did take some very hard times with 2 pandas boys to push me to do it. I literally hit a brick wall and I decided that I couldnt' take much more...

 

Best of luck with your decision!

Stephanie

  momto2pandas said:

Can't believe it, but it looks like my kids will be getting IVIG in three weeks, pending repeat bloodwork. Based on their immune results (below normal range) and history of recurrent/chronic infections, plus PANDAS (and lots of other autommune stuff in ds6), Dr. B feels that there is no reason to wait. I can't get used to the idea. Particularly for ds3, his PANDAS is so mild that I can't even say that I'm absolutely 100% sure about it, and even ds6 is pretty well off as far as PANDAS cases go. Even their infections - though persistent and recurrent - have never caused hospitalization or even much time out of school. Dr. B feels that we should go ahead BEFORE they get sicker, and I guess it makes sense given the labs, but somehow I always thought IVIG was VERY far in the future if things progressed a LOT, and I feel strange about it in kids that basically seem quite normal and healthy. I keep switching between feeling haunted by the thought that we're being too "experimental" on the kids -- and feeling grateful that maybe they're actually going to get "fixed" before they get "broken" in any way that will leave real scars (what a contrast to my own childhood...). People like my Mom keep questioning whether it's really necessary (funny that it's she, of all people, given that she experienced what happened in my untreated childhood!), and I watch the kids playing happily with friends, doing well in school, and looking pretty healthy, and it's hard not to feel like I'm a nut for taking them for IVIG.

 

Does anyone know if PANDAS in immune deficiency ever gets better withOUT IVIG? Or if immune deficiency ever gets better on its own withOUT IVIG? I keep worrying about the risks of treating, but my husband argues that there is more risk in NOT treating... I just wish that I KNEW that that was the case.

 

We're getting CamKinase on them and hope to have the results before proceeding. I think if I see in black and white that their CamK's look PANDAS (and I'm quite sure that they will), I will feel somewhat better about the whole thing.

 

Luckily Dr. B expects insurance to pay so at least financial issues don't weigh in much one way or another.

 

Guess I'm just looking to vent.... and it's all too much to explain to my "real life" friends.

[Stephanie2]

BTW, I'm not sure where you stand on vaccines, but please do your research. If your boys are not that bad, maybe you can nip pandas in the bud. My 5 year old went into a terrible exacerbation when I had his 4 year polio vaccine. I didn't even do the other 2 shots that were scheduled. I was spacing my kids shots out at that point. We are STILL in that exacerbation 14 months later, hence the start of IVIG. Maybe if I had not subjected him to that last shot, things wouldn't have progressed to this. Honestly, I think before that shot he had PANDAS, but after he now has PITAND, which means he reacts to EVERYTHING! Like the doctor said, that shot put his immune system into complete turmoil.

 

Just a thought, since your youngest is 3 and you still have some vaccines ahead of you.

 

Stephanie

[LNN]

We too have been wrestling with IVIG. We did plasmapheresis last summer after a horrendous 10 months (partly because it was easier to get insurance approval for pex and partly because tics were such a dominant symptom). It helped immensely, but thru this winter, we still saw two significant episodes (tho way milder than pre pex) and have finally reached the decision that we can't keep playing Russian Roulette.

 

However, because my son is in remission at the moment, we have the luxury of deciding when to do it. We're not in crisis. We plan to do it at the end of the summer, just prior to the germ-fest of school. I too worry that we'll upset the apple cart. But one wayward sneeze from a classmate could do the same thing and send us into a bad episode. At least if it happens as a result of IVIG, I'll know we've given him a fighting chance of getting well longer term (opposed to having to battle back from another episode with his own deficient immune system).

 

It's not an easy decision. I guess you just have to ask yourself which decision will leave you with the least regrets -not doing it unless he has another episode, or doing it as a preventative measure. Only you know which is the right decision for your family. But trust that you've gotten this far and must be a great advocate for your family, so chances are you'll keep making sound decisions, whatever they might be.

[thereishope]

All I can say is to be comfortable with your decision to follow through on IVIG. Maybe contact SFMom if she doesn't come on here in the next few days. She has little ones that are mild (maybe symptomsless, but Cam K puts into catagory?). She goes to DR K and he had a different take on IVIG for her younger ones. I know every child is different, but you need to feel comfortable with the treatment and it may be best to discuss it with someone in a very similar situation.

 

When was he hoping to do it?

Edited April 3, 2010 by Vickie

[momto2pandas]

I think that I stand where you do with vaccines. When my ds6 was 4, he was pretty much like my ds-almost4 is now. Ds6's pediatrician had deferred many vaccines for a long time due to fears of reactions since his immune system was nutty even at the time (behavioral+physical reactions to rotating door of allergens, illnesses, etc.)...but when we registered for kindergarten, he had to catch up with all of them at once... and shortly afterwards we saw actual OCD in him for the first time, and he was diagnosed with PANDAS.

 

I've already made it clear to the pediatrician that ds3 is done with vaccinations, unless someone can really convince me that it will be safe for him. I don't know what we'll have to do when kindergarten registration comes around in a year, but I'll fight that battle when it comes.

 

Unfortunately, with a weak immune system and proneness to getting sick, being unvaccinated can be kind of scary, too - but he's not launching an immune response to some of them anyway so the cost-benefit ratio doesn't seem so good to me.

 

  Stephanie2 said:

BTW, I'm not sure where you stand on vaccines, but please do your research. If your boys are not that bad, maybe you can nip pandas in the bud. My 5 year old went into a terrible exacerbation when I had his 4 year polio vaccine. I didn't even do the other 2 shots that were scheduled. I was spacing my kids shots out at that point. We are STILL in that exacerbation 14 months later, hence the start of IVIG. Maybe if I had not subjected him to that last shot, things wouldn't have progressed to this. Honestly, I think before that shot he had PANDAS, but after he now has PITAND, which means he reacts to EVERYTHING! Like the doctor said, that shot put his immune system into complete turmoil.

 

Just a thought, since your youngest is 3 and you still have some vaccines ahead of you.

 

Stephanie

[kim]

mom2pandas & all,

 

I was wondering if you would take a look at something I was trying to figure out a while ago. I was specifically seaching for info on "galactose deficiency," (therefore exposing N acetylglucosame ). The first excerpt was an article regarding hep B (these are just excerpts that I saved can't remember the whole article specifically). What struck me, was the "repeated immunization," statement. I was wondering how vaccines along with all of the illness that our children are exposed to in early childhood, plays into the whole scenerio. It seems incredible to me that there ISN"T a dangerous situation that gets set up with the immune system? Apparently, some lose the ability to synthesize galactose as a result of aging, but our little kids (if this is part of the problem)???

 

 

http://jvi.asm.org/cgi/reprint/JVI.01600-07v1.pdf

 

A more exciting explanation for our results is that it is the result of immune

stimulation. That is, it has been shown that a decrease in galactosylation of IgG is

associated with repeated immunization and response to a specific antigen. Surprisingly,

this is the same alteration that we have observed and it strongly suggests that there may

be clonal expansion of a specific set of B cells, presumable those that secrete alpha-gal

antibodies. It is noted that the glycosylation of IgG has shown to be directly associated

with immune function(2). That is, it has been recently reported that IgG mediates pro440

and anti-inflammatory activities through the engagement of its Fc domain (Fc) with

distinct Fc receptors (FcgRs). One type of interaction generates a pro-inflammatory effect

while other interactions generate anti-inflammatory effects. The type of interaction is

dependent upon the presence of terminal sialic acid residues on the N-linked glycan

present on the IgG molecule(18). IgG molecules containing terminal sialic acid molecules

lead to anti-inflammatory responses while IgG molecules lacking terminal sialic acid lead

to a pro-inflammatory response.

 

more on same subject

 

 

http://jdr.sagepub.com/cgi/reprint/84/10/897.pdf

 

 

In many respects, periodontal disease shares some common features

with other chronic inflammatory diseases, particularly with rheumatoid

arthritis, including: production of IgM and IgA rheumatoid factor (Hirsch et

al., 1989); infiltration of inflamed tissue with mainly IgG-secreting plasma

cells (Ogawa et al., 1989); production of auto-antibodies to tissue

components (collagen II in rheumatoid arthritis; collagens I and III in

periodontal disease; Hirsch et al., 1988); similar cytokine profiles (Fujihashi

et al., 1993; Pistoia, 1997); and increased levels of IL-6 (Fujihashi et al.,

1993; Pistoia, 1997).

Extensive structural studies of IgG molecules produced at the site of

chronic inflammation and detectable in the circulation revealed profound

alterations in the glycan moieties. Specifically, deficiencies of some

monosaccharides, especially galactose on IgG, have been described in

human chronic inflammatory diseases, such as rheumatoid arthritis,

inflammatory bowel disease, tuberculosis, and infection with HIV (Mullinax

and Mullinax, 1975; Parekh et al., 1985, 1988; Tomana et al., 1988;

Bodman et al., 1992; Tsuchiya et al., 1993; Rademacher et al., 1994;

Tomana, 1996; Moore et al., 2005). IgG contains one complex-type

oligosaccharide (Fig. 1A) per each heavy chain linked to the conserved

glycosylation site on asparagine 297 within constant region domain 2, which

presumably has a role in maintaining the three-dimensional structure of the

Fc portion of IgG. In IgG with galactose-deficient glycans, the terminally

exposed sugar molecule is N-acetylglucosamine. Analysis of experimental

data has indicated that galactose-deficient IgG is pathogenic (Rademacher et

al., 1994): Galactose-deficient IgG binds to the mannan-binding lectin and

thus activates the complement cascade by the lectin pathway (Malhotra et

al., 1995). Furthermore, glycans on IgG molecules affect binding and

internalization by Fc receptors expressed on phagocytic cells (Krapp et al.,

2003) and, thus, influence opsonization of antigens by phagocytosis.

 

 

http://www3.interscience.wiley.com/journal...470730/abstract

 

Abstract

Patients with rheumatoid arthritis have a reduced prevalence of immunoglobulin G (IgG) oligosaccharide chains terminating in galactose, thus exposing N-acetylglucosamine. We analyzed IgG glycosylation in patients with rheumatoid arthritis, patients with early synovitis, and in controls by means of isoelectric focusing and lectin-affinoblotting. The ratio of N-terminal N-acetylglucosamine and galactose was determined using specific biotin-labeled lectins. The IgG glycosylation state may well be of clinical value in the differential diagnosis of patients presenting with early synovitis.

 

http://www3.interscience.wiley.com/journal...=1&SRETRY=0

 

ABSTRACT

 

 

The relationship between increased levels of IgG oligosaccharide chains lacking galactose (GO) and the development of rheumatoid arthritis is unclear. In order to further our understanding of the observed correlation between raised serum GO and arthritis, we have studied GO levels in arthritis prone and non-susceptible (i.e., non-arthritis-prone) mice and the effects on GO of mycobacterial antigens, which have been postulated to play a role in the early events leading to the development of arthritis. We have shown that different age-matched mouse strains have characteristic "resting" levels of GO which (in six out of seven strains of mice) increase with age. We have also shown that these increases can be enhanced by immunization of arthritis-prone strains of mice with an adjuvant containing mycobacteria (Freund's complete adjuvant (FCA)), suggesting that deflects in the ability to regulate these GO changes may be related to susceptibility to arthritis.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/1146794...ogdbfrom=pubmed

 

 

Glycoengineering of therapeutic glycoproteins: in vitro galactosylation and sialylation of glycoproteins with terminal N-acetylglucosamine and galactose residues.

Raju TS, Briggs JB, Chamow SM, Winkler ME, Jones AJ.

 

Analytical Chemistry, Genentech Inc., One DNA Way, South San Francisco, California 94080, USA. sraju@gene.com

 

Therapeutic glycoproteins produced in different host cells by recombinant DNA technology often contain terminal GlcNAc and Gal residues. Such glycoproteins clear rapidly from the serum as a consequence of binding to the mannose receptor and/or the asialoglycoprotein receptor in the liver. To increase the serum half-life of these glycoproteins, we carried out in vitro glycosylation experiments using TNFR-IgG, an immunoadhesin molecule, as a model therapeutic glycoprotein. TNFR-IgG is a disulfide-linked dimer of a polypeptide composed of the extracellular portion of the human type 1 (p55) tumor necrosis factor receptor (TNFR) fused to the hinge and Fc regions of the human IgG(1) heavy chain. This bivalent antibody-like molecule contains four N-glycosylation sites per polypeptide, three in the receptor portion and one in the Fc. The heterogeneous N-linked oligosaccharides of TNFR-IgG contain sialic acid (Sia), Gal, and GlcNAc as terminal sugar residues. To increase the level of terminal sialylation, we regalactosylated and/or resialylated TNFR-IgG using beta-1,4-galactosyltransferase (beta1,4GT) and/or alpha-2,3-sialyltransferase (alpha2,3ST). Treatment of TNFR-IgG with beta1,4GT and UDP-Gal, in the presence of MnCl(2), followed by MALDI-TOF-MS analysis of PNGase F-released N-glycans showed that the number of oligosaccharides with terminal GlcNAc residues was significantly decreased with a concomitant increase in the number of terminal Gal residues. Similar treatment of TNFR-IgG with alpha2,3ST and CMP-sialic acid (CMP-Sia), in the presence of MnCl(2), produced a molecule with an approximately 11% increase in the level of terminal sialylation but still contained oligosaccharides with terminal GlcNAc residues. When TNFR-IgG was treated with a combination of beta1,4GT and alpha2,3ST (either in a single step or in a stepwise fashion), the level of terminal sialylation was increased by approximately 20-23%. These results suggest that in vitro galactosylation and sialylation of therapeutic glycoproteins with terminal GlcNAc and Gal residues can be achieved in a single step, and the results are similar to those for the stepwise reaction. This type of in vitro glycosylation is applicable to other glycoproteins containing terminal GlcNAc and Gal residues and could prove to be useful in increasing the serum half-life of therapeutic glycoproteins.

[Fixit]

How badd were you sons tics before plaz? My boys were about 7 1/2 at start and am lining ducks up to medicate..i have script for cholidine

found myco p..but i wonder about co-infect

 

after plaz how much better did they get 30-50%?

for us nothing not worthy on starting clarith..we did burst too...about 3 days in son developed screech....we are still dealng with that..almost went away after a week but lost fillig and so dental work

we started augmetnin aoubt 2-3 weeks in and it was like a miracle.....no one /or most wouldn't notice tics (they did still rise with excitedment) but it was so nice to be by him w/o the constant movement.....But like someone here mentiond...nothing is easy for me and ds seems to allergic...severe joint pain and so tics are back and so is occasional screech

 

doing zith right now...so i don't know...i have to keep moving forward lining things up incase, and so it goes, doen't work...

 

how much have things relapesed?

can you do another plaz?

i'm sorry,,,how old is your boy again???

 

 

  LLM said:

We too have been wrestling with IVIG. We did plasmapheresis last summer after a horrendous 10 months (partly because it was easier to get insurance approval for pex and partly because tics were such a dominant symptom). It helped immensely, but thru this winter, we still saw two significant episodes (tho way milder than pre pex) and have finally reached the decision that we can't keep playing Russian Roulette.

 

However, because my son is in remission at the moment, we have the luxury of deciding when to do it. We're not in crisis. We plan to do it at the end of the summer, just prior to the germ-fest of school. I too worry that we'll upset the apple cart. But one wayward sneeze from a classmate could do the same thing and send us into a bad episode. At least if it happens as a result of IVIG, I'll know we've given him a fighting chance of getting well longer term (opposed to having to battle back from another episode with his own deficient immune system).

 

It's not an easy decision. I guess you just have to ask yourself which decision will leave you with the least regrets -not doing it unless he has another episode, or doing it as a preventative measure. Only you know which is the right decision for your family. But trust that you've gotten this far and must be a great advocate for your family, so chances are you'll keep making sound decisions, whatever they might be.

[matis_mom]

  momto2pandas said:

Can't believe it, but it looks like my kids will be getting IVIG in three weeks, pending repeat bloodwork. Based on their immune results (below normal range) and history of recurrent/chronic infections, plus PANDAS (and lots of other autommune stuff in ds6), Dr. B feels that there is no reason to wait. I can't get used to the idea. Particularly for ds3, his PANDAS is so mild that I can't even say that I'm absolutely 100% sure about it, and even ds6 is pretty well off as far as PANDAS cases go. Even their infections - though persistent and recurrent - have never caused hospitalization or even much time out of school. Dr. B feels that we should go ahead BEFORE they get sicker, and I guess it makes sense given the labs, but somehow I always thought IVIG was VERY far in the future if things progressed a LOT, and I feel strange about it in kids that basically seem quite normal and healthy. I keep switching between feeling haunted by the thought that we're being too "experimental" on the kids -- and feeling grateful that maybe they're actually going to get "fixed" before they get "broken" in any way that will leave real scars (what a contrast to my own childhood...). People like my Mom keep questioning whether it's really necessary (funny that it's she, of all people, given that she experienced what happened in my untreated childhood!), and I watch the kids playing happily with friends, doing well in school, and looking pretty healthy, and it's hard not to feel like I'm a nut for taking them for IVIG.

 

Does anyone know if PANDAS in immune deficiency ever gets better withOUT IVIG? Or if immune deficiency ever gets better on its own withOUT IVIG? I keep worrying about the risks of treating, but my husband argues that there is more risk in NOT treating... I just wish that I KNEW that that was the case.

 

We're getting CamKinase on them and hope to have the results before proceeding. I think if I see in black and white that their CamK's look PANDAS (and I'm quite sure that they will), I will feel somewhat better about the whole thing.

 

Luckily Dr. B expects insurance to pay so at least financial issues don't weigh in much one way or another.

 

Guess I'm just looking to vent.... and it's all too much to explain to my "real life" friends.

Well, what exactly ARE the risk associated with IVIG? I know they are mentioned over and over, but I don't know exactly what they are! Anyone?

As for going through with it or not, that is a tough question. For us, there are no other immune problems, and antibiotics seem to be taking care of most of it, so we are waiting. Dr. Latimer says some patients do make a recovery without a need for IVIG. She does not seem our son needs it at this point, so we are going with that. But if you trust your doctor, and he believes they need it, then I would do it. I am just thinking of so many parents in this forum who wish they had know about PANDAS and gotten the right treatment years ago when their kids were little.

[momto2pandas]

The side effects that are listed are things like the very small chance of a reaction to the IVIG, infection at the site, stuff like that -- but the effects that worry me more are the anecdotal reports of things getting stirred up and made worse, weird old symptoms showing up, etc. It may well be for the best in the long run, but I'm not looking forward to a roller coaster ride and all of the doubts that I'm sure come along with that....

 

 

  mati said:

  momto2pandas said:

Can't believe it, but it looks like my kids will be getting IVIG in three weeks, pending repeat bloodwork. Based on their immune results (below normal range) and history of recurrent/chronic infections, plus PANDAS (and lots of other autommune stuff in ds6), Dr. B feels that there is no reason to wait. I can't get used to the idea. Particularly for ds3, his PANDAS is so mild that I can't even say that I'm absolutely 100% sure about it, and even ds6 is pretty well off as far as PANDAS cases go. Even their infections - though persistent and recurrent - have never caused hospitalization or even much time out of school. Dr. B feels that we should go ahead BEFORE they get sicker, and I guess it makes sense given the labs, but somehow I always thought IVIG was VERY far in the future if things progressed a LOT, and I feel strange about it in kids that basically seem quite normal and healthy. I keep switching between feeling haunted by the thought that we're being too "experimental" on the kids -- and feeling grateful that maybe they're actually going to get "fixed" before they get "broken" in any way that will leave real scars (what a contrast to my own childhood...). People like my Mom keep questioning whether it's really necessary (funny that it's she, of all people, given that she experienced what happened in my untreated childhood!), and I watch the kids playing happily with friends, doing well in school, and looking pretty healthy, and it's hard not to feel like I'm a nut for taking them for IVIG.

 

Does anyone know if PANDAS in immune deficiency ever gets better withOUT IVIG? Or if immune deficiency ever gets better on its own withOUT IVIG? I keep worrying about the risks of treating, but my husband argues that there is more risk in NOT treating... I just wish that I KNEW that that was the case.

 

We're getting CamKinase on them and hope to have the results before proceeding. I think if I see in black and white that their CamK's look PANDAS (and I'm quite sure that they will), I will feel somewhat better about the whole thing.

 

Luckily Dr. B expects insurance to pay so at least financial issues don't weigh in much one way or another.

 

Guess I'm just looking to vent.... and it's all too much to explain to my "real life" friends.

Well, what exactly ARE the risk associated with IVIG? I know they are mentioned over and over, but I don't know exactly what they are! Anyone?

As for going through with it or not, that is a tough question. For us, there are no other immune problems, and antibiotics seem to be taking care of most of it, so we are waiting. Dr. Latimer says some patients do make a recovery without a need for IVIG. She does not seem our son needs it at this point, so we are going with that. But if you trust your doctor, and he believes they need it, then I would do it. I am just thinking of so many parents in this forum who wish they had know about PANDAS and gotten the right treatment years ago when their kids were little.

[Stephanie2]

As for Kindergarten, I don't know what state you live in, but here in Florida you can use either a medical exemption (not sure how you acquire this and what the requirements are) or a religious exemption. I probably could have pursued a medical exemption as my son came up positive for an egg allergy on an IgG food allergy panel, but I just found it just as easy to go to the local health department and get the religious waiver for both of my boys. They did not ask any questions and so far at preschool they have not asked any questions. There are many parents nowadays who are not vaccinating so it is not as "stigmatizing" as it may have once been. Not to mention, my kids' preschool knows that both of my kids have multiple health problems and I told them that they both regressed after vaccines. How can anyone argue with that, ya know?

 

Whatever you decide, good luck with your decisions! So hard when these little lives are in our hands! I always wonder what they would decide for themselves if they were little adults. Will they one day look at me and say, "thanks mom" or will they say "mom, you were crazy to subject me to all that stuff"! I know my 5 year old has not had a typical childhood and is constantly at the docs/therapists office. I just hope one day he will understand, and just be healthy and happy...

 

Stephanie

[momto2pandas]

Kim - This is really interesting stuff and I think that you're on to something here. I wonder why, from an evolutionary point of view, a switch would be made to decreased galactosylation of IgG with repeat challenge by the same antigen. Is the proinflammatory response thus generated somehow adaptive?

 

It's interesting to me that one of the articles calls TB a "chronic inflammatory disease". Particularly interesting to me given that I was found to have TB while I had anorexia nervosa and the AN cleared when the TB was treated. I never bothered to research much about TB (when I had it I was so young - and it was pre-internet!).

 

Vaccines have obviously done the world a ton of good, but it seems like that science still needs to evolve some more. Or, it could have little to do with vaccinations, and have more to do with the fact that it in our highly mobile and population-dense culture, we get too much exposure to the same bugs over and over again. If it were just that, though, you would expect to see more inflammatory diseases in very population dense and infection-prone cultures like you see in e.g. India, and instead, inflammatory diseases seem mostly be to a plague of the "developed" world.

 

 

  kim said:

mom2pandas & all,

 

I was wondering if you would take a look at something I was trying to figure out a while ago. I was specifically seaching for info on "galactose deficiency," (therefore exposing N acetylglucosame ). The first excerpt was an article regarding hep B (these are just excerpts that I saved can't remember the whole article specifically). What struck me, was the "repeated immunization," statement. I was wondering how vaccines along with all of the illness that our children are exposed to in early childhood, plays into the whole scenerio. It seems incredible to me that there ISN"T a dangerous situation that gets set up with the immune system? Apparently, some lose the ability to synthesize galactose as a result of aging, but our little kids (if this is part of the problem)???

 

 

http://jvi.asm.org/cgi/reprint/JVI.01600-07v1.pdf

 

A more exciting explanation for our results is that it is the result of immune

stimulation. That is, it has been shown that a decrease in galactosylation of IgG is

associated with repeated immunization and response to a specific antigen. Surprisingly,

this is the same alteration that we have observed and it strongly suggests that there may

be clonal expansion of a specific set of B cells, presumable those that secrete alpha-gal

antibodies. It is noted that the glycosylation of IgG has shown to be directly associated

with immune function(2). That is, it has been recently reported that IgG mediates pro440

and anti-inflammatory activities through the engagement of its Fc domain (Fc) with

distinct Fc receptors (FcgRs). One type of interaction generates a pro-inflammatory effect

while other interactions generate anti-inflammatory effects. The type of interaction is

dependent upon the presence of terminal sialic acid residues on the N-linked glycan

present on the IgG molecule(18). IgG molecules containing terminal sialic acid molecules

lead to anti-inflammatory responses while IgG molecules lacking terminal sialic acid lead

to a pro-inflammatory response.

 

more on same subject

 

 

http://jdr.sagepub.com/cgi/reprint/84/10/897.pdf

 

 

In many respects, periodontal disease shares some common features

with other chronic inflammatory diseases, particularly with rheumatoid

arthritis, including: production of IgM and IgA rheumatoid factor (Hirsch et

al., 1989); infiltration of inflamed tissue with mainly IgG-secreting plasma

cells (Ogawa et al., 1989); production of auto-antibodies to tissue

components (collagen II in rheumatoid arthritis; collagens I and III in

periodontal disease; Hirsch et al., 1988); similar cytokine profiles (Fujihashi

et al., 1993; Pistoia, 1997); and increased levels of IL-6 (Fujihashi et al.,

1993; Pistoia, 1997).

Extensive structural studies of IgG molecules produced at the site of

chronic inflammation and detectable in the circulation revealed profound

alterations in the glycan moieties. Specifically, deficiencies of some

monosaccharides, especially galactose on IgG, have been described in

human chronic inflammatory diseases, such as rheumatoid arthritis,

inflammatory bowel disease, tuberculosis, and infection with HIV (Mullinax

and Mullinax, 1975; Parekh et al., 1985, 1988; Tomana et al., 1988;

Bodman et al., 1992; Tsuchiya et al., 1993; Rademacher et al., 1994;

Tomana, 1996; Moore et al., 2005). IgG contains one complex-type

oligosaccharide (Fig. 1A) per each heavy chain linked to the conserved

glycosylation site on asparagine 297 within constant region domain 2, which

presumably has a role in maintaining the three-dimensional structure of the

Fc portion of IgG. In IgG with galactose-deficient glycans, the terminally

exposed sugar molecule is N-acetylglucosamine. Analysis of experimental

data has indicated that galactose-deficient IgG is pathogenic (Rademacher et

al., 1994): Galactose-deficient IgG binds to the mannan-binding lectin and

thus activates the complement cascade by the lectin pathway (Malhotra et

al., 1995). Furthermore, glycans on IgG molecules affect binding and

internalization by Fc receptors expressed on phagocytic cells (Krapp et al.,

2003) and, thus, influence opsonization of antigens by phagocytosis.

 

 

http://www3.interscience.wiley.com/journal...470730/abstract

 

Abstract

Patients with rheumatoid arthritis have a reduced prevalence of immunoglobulin G (IgG) oligosaccharide chains terminating in galactose, thus exposing N-acetylglucosamine. We analyzed IgG glycosylation in patients with rheumatoid arthritis, patients with early synovitis, and in controls by means of isoelectric focusing and lectin-affinoblotting. The ratio of N-terminal N-acetylglucosamine and galactose was determined using specific biotin-labeled lectins. The IgG glycosylation state may well be of clinical value in the differential diagnosis of patients presenting with early synovitis.

 

http://www3.interscience.wiley.com/journal...=1&SRETRY=0

 

ABSTRACT

 

 

The relationship between increased levels of IgG oligosaccharide chains lacking galactose (GO) and the development of rheumatoid arthritis is unclear. In order to further our understanding of the observed correlation between raised serum GO and arthritis, we have studied GO levels in arthritis prone and non-susceptible (i.e., non-arthritis-prone) mice and the effects on GO of mycobacterial antigens, which have been postulated to play a role in the early events leading to the development of arthritis. We have shown that different age-matched mouse strains have characteristic "resting" levels of GO which (in six out of seven strains of mice) increase with age. We have also shown that these increases can be enhanced by immunization of arthritis-prone strains of mice with an adjuvant containing mycobacteria (Freund's complete adjuvant (FCA)), suggesting that deflects in the ability to regulate these GO changes may be related to susceptibility to arthritis.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/1146794...ogdbfrom=pubmed

 

 

Glycoengineering of therapeutic glycoproteins: in vitro galactosylation and sialylation of glycoproteins with terminal N-acetylglucosamine and galactose residues.

Raju TS, Briggs JB, Chamow SM, Winkler ME, Jones AJ.

 

Analytical Chemistry, Genentech Inc., One DNA Way, South San Francisco, California 94080, USA. sraju@gene.com

 

Therapeutic glycoproteins produced in different host cells by recombinant DNA technology often contain terminal GlcNAc and Gal residues. Such glycoproteins clear rapidly from the serum as a consequence of binding to the mannose receptor and/or the asialoglycoprotein receptor in the liver. To increase the serum half-life of these glycoproteins, we carried out in vitro glycosylation experiments using TNFR-IgG, an immunoadhesin molecule, as a model therapeutic glycoprotein. TNFR-IgG is a disulfide-linked dimer of a polypeptide composed of the extracellular portion of the human type 1 (p55) tumor necrosis factor receptor (TNFR) fused to the hinge and Fc regions of the human IgG(1) heavy chain. This bivalent antibody-like molecule contains four N-glycosylation sites per polypeptide, three in the receptor portion and one in the Fc. The heterogeneous N-linked oligosaccharides of TNFR-IgG contain sialic acid (Sia), Gal, and GlcNAc as terminal sugar residues. To increase the level of terminal sialylation, we regalactosylated and/or resialylated TNFR-IgG using beta-1,4-galactosyltransferase (beta1,4GT) and/or alpha-2,3-sialyltransferase (alpha2,3ST). Treatment of TNFR-IgG with beta1,4GT and UDP-Gal, in the presence of MnCl(2), followed by MALDI-TOF-MS analysis of PNGase F-released N-glycans showed that the number of oligosaccharides with terminal GlcNAc residues was significantly decreased with a concomitant increase in the number of terminal Gal residues. Similar treatment of TNFR-IgG with alpha2,3ST and CMP-sialic acid (CMP-Sia), in the presence of MnCl(2), produced a molecule with an approximately 11% increase in the level of terminal sialylation but still contained oligosaccharides with terminal GlcNAc residues. When TNFR-IgG was treated with a combination of beta1,4GT and alpha2,3ST (either in a single step or in a stepwise fashion), the level of terminal sialylation was increased by approximately 20-23%. These results suggest that in vitro galactosylation and sialylation of therapeutic glycoproteins with terminal GlcNAc and Gal residues can be achieved in a single step, and the results are similar to those for the stepwise reaction. This type of in vitro glycosylation is applicable to other glycoproteins containing terminal GlcNAc and Gal residues and could prove to be useful in increasing the serum half-life of therapeutic glycoproteins.

[momto2pandas]

I think you hit the nail on the head with your last paragraph... it is hard to make big decisions for little people, but then if you wait until they're big people to do anything, you might miss a very positive opportunity.

 

 

  Stephanie2 said:

As for Kindergarten, I don't know what state you live in, but here in Florida you can use either a medical exemption (not sure how you acquire this and what the requirements are) or a religious exemption. I probably could have pursued a medical exemption as my son came up positive for an egg allergy on an IgG food allergy panel, but I just found it just as easy to go to the local health department and get the religious waiver for both of my boys. They did not ask any questions and so far at preschool they have not asked any questions. There are many parents nowadays who are not vaccinating so it is not as "stigmatizing" as it may have once been. Not to mention, my kids' preschool knows that both of my kids have multiple health problems and I told them that they both regressed after vaccines. How can anyone argue with that, ya know?

 

Whatever you decide, good luck with your decisions! So hard when these little lives are in our hands! I always wonder what they would decide for themselves if they were little adults. Will they one day look at me and say, "thanks mom" or will they say "mom, you were crazy to subject me to all that stuff"! I know my 5 year old has not had a typical childhood and is constantly at the docs/therapists office. I just hope one day he will understand, and just be healthy and happy...

 

Stephanie

[kim]

momto2,

 

Take a look at these. Wondering about this whole pathway and how IVIG may improve if this situation is involved?

 

In regards to above posts, some things I'm wondering......

 

Galactose-deficient IgG binds to the mannan-binding lectin and

thus activates the complement cascade by the lectin pathway

 

It appears the mannose residues in Mycobacterium tuberculosis are important in it's antigenicity. If a state of deficient glactose IgG exists, would a hyperimmune response to TB infection occur?

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC96927/

 

 

Mannan-binding lectin pathway

 

The Mannan-binding lectin pathway (also known as the Ali/Krueger Pathway) is homologous to the classical complement pathway. This pathway uses a protein similar to C1q of the classical complement pathway, which binds to mannose residues and other sugars in a pattern that allows binding on multiple pathogens. Mannan-binding lectin (MBL; also called mannose-binding lectin) is a protein belonging to the collectin family that is produced by the liver and can initiate the complement cascade by binding to pathogen surfaces.

http://en.wikipedia.org/wiki/Mannan-binding_lectin_pathway

 

 

and

 

fasting may increase the glycosylation status of IgG . I know it's probably very hard to think of any case of AN as being beneficial in any way, but I wonder if it's possible that the body fighting to stabilize in some cases? Maybe a protective mechanism that doesn't reverse properly when it's no longer required? Since your AN was not associated with body image problems, it makes me even more curious.

 

http://rheumatology.oxfordjournals.org/cgi...nt/35/2/117.pdf

CHANGES IN GLYCOSYLATION OF IgG DURING FASTING IN

PATIENTS WITH RHEUMATOID ARTHRITIS

 

 

Also, the possible Crohn's connection in this pathway sure seems noteworthy (bolding mine)

 

http://en.wikipedia.org/wiki/Anti-saccharo...siae_antibodies

 

Anti-Saccharomyces cerevisiae antibodies (ASCA), along with perinuclear antineutrophil cytoplasmic antibodies (pANCA), are among the two most useful and often discriminating markers for colitis.[1] ASCA tends to recognize Crohn's disease more frequently, whereas pANCA tend to recognize ulcerative colitis.[2]

 

ASCA antibodies react to the following yeast proteins

 

Mannans[3]

 

 

edited to remove my edit!

Edited April 4, 2010 by kim

[sf_mom]

We've had a very positive outcome and pray daily it continues. Our son has vastly improved in areas we didn't realize were related to PANDAS. We have no regrets. We will retreat if necessary....

 

REMEMBER, the first couple of weeks post treatment can be rough. Only retreat if and when the baseline adjusts downward and try to wait a minimum of 8 to 12 weeks post IVIG before attempting another. We are seeing a new baseline adjustment upwards between weeks 9 to 12 post last treatment.

 

Good luck and look forward to hearing about your progress.

 

-Wendy