EndoS from strep pyogenes

[kim]

Just ran across this quite unexpectedly and have absolutely no more time right now. Does anyone have any idea's here? excerpt below

 

http://www.ncbi.nlm.nih.gov/pubmed/1975821...ogdbfrom=pubmed

 

 

Ann N Y Acad Sci. 2009 Sep;1173:664-9.

 

Sugar-free antibodies--the bacterial solution to autoimmunity?

Allhorn M, Collin M.

 

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

 

The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease.

[Buster]

I recommend starting here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/

 

Buster

 

Just ran across this quite unexpectedly and have absolutely no more time right now. Does anyone have any idea's here? excerpt below

 

http://www.ncbi.nlm.nih.gov/pubmed/1975821...ogdbfrom=pubmed

 

 

Ann N Y Acad Sci. 2009 Sep;1173:664-9.

 

Sugar-free antibodies--the bacterial solution to autoimmunity?

Allhorn M, Collin M.

 

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

 

The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease.

[sf_mom]

I find it very interesting and plan to ask Lewis about this article and Romy's low IgGs!

 

-Wendy

 

I recommend starting here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/

 

Buster

 

Just ran across this quite unexpectedly and have absolutely no more time right now. Does anyone have any idea's here? excerpt below

 

http://www.ncbi.nlm.nih.gov/pubmed/1975821...ogdbfrom=pubmed

 

 

Ann N Y Acad Sci. 2009 Sep;1173:664-9.

 

Sugar-free antibodies--the bacterial solution to autoimmunity?

Allhorn M, Collin M.

 

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

 

The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease.

[momofgirls]

Hard to read but if I understand it correctly, Wendy, your thoughts we discussed earlier are correct. The toxins wipe out the immune system right?

 

 

 

 

 

I find it very interesting and plan to ask Lewis about this article and Romy's low IgGs!

 

-Wendy

 

I recommend starting here:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC100124/

 

Buster

 

Just ran across this quite unexpectedly and have absolutely no more time right now. Does anyone have any idea's here? excerpt below

 

http://www.ncbi.nlm.nih.gov/pubmed/1975821...ogdbfrom=pubmed

 

 

Ann N Y Acad Sci. 2009 Sep;1173:664-9.

 

Sugar-free antibodies--the bacterial solution to autoimmunity?

Allhorn M, Collin M.

 

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

 

The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease.

[sf_mom]

I need an interpreter for this article. 'BUSTER/KIM' are you able to summarize simply. I've printed and plan to bring along to the next appointment Dr. Lewis if I can figure it out. BUT, yes it does appear toxin has a 'broad immunoglobulin - degrading activity'!?

 

-Wendy

[peglem]

So, is it saying that strep excretes enzymes that destroy or neutralize immunoglobulins? Checking to see if I got that right. If that's it, wow! Another piece of the puzzle.

[Buster]

Okay, I'll try a translation -- please jump in...

 

In 2001, Collin showed in http://iai.asm.org/cgi/reprint/69/11/7187.pdf that GABHS produced two enzymes (SpeB and EndoS) that acted in different ways to neutralize Immunoglobulins.

 

In 2009, Egesten and Collin found that SpeB actually disables most of the antibacterial chemokines (inflammatory chemicals) and degrades/destroys the ability of epithelial cells to advertise bacterial infections. http://www.plosone.org/article/info:doi%2F...al.pone.0004769

 

Also in 2009, Allhorn and Collin http://www3.interscience.wiley.com/cgi-bin...582871/PDFSTART found that EndoS is specific for IgG 1-4 whereas SpeB seems to go after IgM, IgA, IgG, IgD, ... When EndoS bound to IgG antibodies, the antibodies did not "signal" phagocytes to "kill bacteria" -- essentially EndoS disables the IgG's ability to signal bacteria (and cells) for phagocytosis.

 

What was actually the most fascinating part of the article is that for auto-immune diseases, EndoS might be therapeutic by inhibiting the binding/activation of IgG antibodies that are oriented towards the host. This is very very preliminary work, but they showed that adding EndoS could cause IgG to stop attacking host cell -- and put mice in remission who had EAE or rheumatoid arthritis. Again, this is WAY too early here to know the real effects.

 

Hope that helps. That's my brief interpretation of the papers.

 

Buster

 

http://www.ncbi.nlm.nih.gov/pubmed/1975821...ogdbfrom=pubmed

 

 

Ann N Y Acad Sci. 2009 Sep;1173:664-9.

 

Sugar-free antibodies--the bacterial solution to autoimmunity?

Allhorn M, Collin M.

 

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

 

The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease.

[peglem]

Thank you Kim and Buster- amazing stuff!

[sf_mom]

Thanks Buster, your perspective/interpretation is always very helpful.

 

-Wendy

 

Okay, I'll try a translation -- please jump in...

 

In 2001, Collin showed in http://iai.asm.org/cgi/reprint/69/11/7187.pdf that GABHS produced two enzymes (SpeB and EndoS) that acted in different ways to neutralize Immunoglobulins.

 

In 2009, Egesten and Collin found that SpeB actually disables most of the antibacterial chemokines (inflammatory chemicals) and degrades/destroys the ability of epithelial cells to advertise bacterial infections. http://www.plosone.org/article/info:doi%2F...al.pone.0004769

 

Also in 2009, Allhorn and Collin http://www3.interscience.wiley.com/cgi-bin...582871/PDFSTART found that EndoS is specific for IgG 1-4 whereas SpeB seems to go after IgM, IgA, IgG, IgD, ... When EndoS bound to IgG antibodies, the antibodies did not "signal" phagocytes to "kill bacteria" -- essentially EndoS disables the IgG's ability to signal bacteria (and cells) for phagocytosis.

 

What was actually the most fascinating part of the article is that for auto-immune diseases, EndoS might be therapeutic by inhibiting the binding/activation of IgG antibodies that are oriented towards the host. This is very very preliminary work, but they showed that adding EndoS could cause IgG to stop attacking host cell -- and put mice in remission who had EAE or rheumatoid arthritis. Again, this is WAY too early here to know the real effects.

 

Hope that helps. That's my brief interpretation of the papers.

 

Buster

 

http://www.ncbi.nlm.nih.gov/pubmed/1975821...ogdbfrom=pubmed

 

 

Ann N Y Acad Sci. 2009 Sep;1173:664-9.

 

Sugar-free antibodies--the bacterial solution to autoimmunity?

Allhorn M, Collin M.

 

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

 

The enzyme EndoS from Streptococcus pyogenes is an immunomodulatory molecule hydrolyzing the conserved glycans in the effector part of immunoglobulin G (IgG). EndoS is remarkably specific for IgG, and hydrolysis has profound effects on IgG effector functions. EndoS pretreatment of IgG, or direct administration to animals with experimental antibody-mediated autoimmune diseases, inhibits development of disease or cures animals from established disease.

[kim]

What a horrible time to not have any computer time.

 

Buster, this is what I'm trying to figure out at the moment. As alway,s thanks so much for your expertise!

 

An inactive form of EndoS, obtained by site-directed mutagenesis

 

from here

 

http://www.ncbi.nlm.nih.gov/pubmed/1818329...ogdbfrom=pubmed

 

SF mom, this really makes me wonder about your hunt for a certain strain of strep and seems like it could account for some of the differences we see.

 

I'm going to see if I can find the whole paper and spend a couple of wee morning hours to figure out that sentence (only 1/2 kidding). Thanks everyone!

[sf_mom]

Kim as you know, I AM on the hunt for the strain. AND, I'm trying to communicate this to the 'higher powers' of the strep world. I'm making a little headway in hopes that they may test my younger son for the strain. I will officially up date when I can. BUT, for now, I would be forever grateful for your interpretation of the study. If its actually depleting the IgGs..... Romy has all the markers of the S. Pyogenes doing its job on his immune system.

 

-Wendy

[momto2pandas]

It seems to me that what they are saying is that the active form, i.e. the form that hydrolyzes the heavy chain glycan of IgG, binds IgG with low affinity, but if they selectively mutate the EndoS to be "inactive", which I assume means that it does not hydrolyze, then it has higher binding affinity for IgG (i.e. sticks to it longer). I did not read the whole article, but I assume that this is relevant to the last sentence in the abstract where it talks about using engineered EndoS for IgG purification/detection, since high affinity would be better for that purpose. It might also be better for therapeutic purposes that IgG be bound with high affinity, if this binding prevents attacks on the host - what doesn't make sense to me about that, though, is that the wild-type form seems to prevent binding to host antigens effectively as is by hydrolyzing that heavy chain glycan, so that the selective mutation doesn't seem necessary.

 

I didn't read the whole article so I may be wrong on my assumptions, but that's my best interpretation of the abstract.

 

 

What a horrible time to not have any computer time.

 

Buster, this is what I'm trying to figure out at the moment. As alway,s thanks so much for your expertise!

 

An inactive form of EndoS, obtained by site-directed mutagenesis

 

from here

 

http://www.ncbi.nlm.nih.gov/pubmed/1818329...ogdbfrom=pubmed

 

SF mom, this really makes me wonder about your hunt for a certain strain of strep and seems like it could account for some of the differences we see.

 

I'm going to see if I can find the whole paper and spend a couple of wee morning hours to figure out that sentence (only 1/2 kidding). Thanks everyone!

[kim]

Momto2PANDAS,

 

Thanks for that.

 

Wondering if you could comment on something else? It says "EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG."

 

Would EndoS then be "curing" autoimmune disease by breaking down IgG that would be bound in an imbedded or circulating immune complex? I take it the risk would be infection, if this were a systemic treatment?

 

N acetyl glucosamine has always been of particular interest to me, as I've wondered if it couldn't be an important substance in blocking the antibody attack that seems to be taking place. There is some info here that I would really luv your take on, since it appears to be the strep reactive epitope and it has been found to block T cell reactivity. Now I'm looking at chitobiose in the IgG, and trying to figure out how that fits in the picture.

 

http://www.latitudes.org/forums/index.php?...etylglucosamine

 

I would be taking this in a heart beat, if I could find a product that I trusted for purity. I'm hesitant as I feel it would probably require a fairly decent amt.

 

 

Wendy,

 

Remember my level of knowledge here (minimal!) but it sure seems like it this could be playing a part. Please let us know if this is of any interest to Romy's Dr. and what his take on it is.

 

I know how frustrating it is to feel that you're really on to something and not have anyone who is on the same page. It's hard when there are so many idea's with some common end points, but different paths leading there. The way all 3 of the boys were affected seems to say something really important and I hope their story catches someone's interest. Hang in there. Maybe collectively, we'll make a difference here one way or another some day.

[nevergiveup]

Kim.

 

We use to take it, I got it from Allergy Research Group. Any issues with this company's purity? Heard it helps wth ms.

 

 

Momto2PANDAS,

 

Thanks for that.

 

Wondering if you could comment on something else? It says "EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG."

 

Would EndoS then be "curing" autoimmune disease by breaking down IgG that would be bound in an imbedded or circulating immune complex? I take it the risk would be infection, if this were a systemic treatment?

 

N acetyl glucosamine has always been of particular interest to me, as I've wondered if it couldn't be an important substance in blocking the antibody attack that seems to be taking place. There is some info here that I would really luv your take on, since it appears to be the strep reactive epitope and it has been found to block T cell reactivity. Now I'm looking at chitobiose in the IgG, and trying to figure out how that fits in the picture.

 

http://www.latitudes.org/forums/index.php?...etylglucosamine

 

I would be taking this in a heart beat, if I could find a product that I trusted for purity. I'm hesitant as I feel it would probably require a fairly decent amt.

 

 

Wendy,

 

Remember my level of knowledge here (minimal!) but it sure seems like it this could be playing a part. Please let us know if this is of any interest to Romy's Dr. and what his take on it is.

 

I know how frustrating it is to feel that you're really on to something and not have anyone who is on the same page. It's hard when there are so many idea's with some common end points, but different paths leading there. The way all 3 of the boys were affected seems to say something really important and I hope their story catches someone's interest. Hang in there. Maybe collectively, we'll make a difference here one way or another some day.

[momto2pandas]

Hi Kim, Just noticed that you directed this to me. Your take re. EndoS is my take as well, but I haven't yet read the article, just the abstract. Unfortunately, the cost of treating autoimmune disease sometimes is increased susceptibility to infection (steroids, anti-TNF, anti-IL drugs, etc.). I'd love to take some time looking at your other references, too, but it will probably have to be after I finish my Christmas shopping at this point! We are traveling starting this week-end so frazzle-time is here...but I look forward to doing the reading.

 

 

Momto2PANDAS,

 

Thanks for that.

 

Wondering if you could comment on something else? It says "EndoS that hydrolyzes the chitobiose core of the asparagine-linked glycan on the heavy chain of human IgG."

 

Would EndoS then be "curing" autoimmune disease by breaking down IgG that would be bound in an imbedded or circulating immune complex? I take it the risk would be infection, if this were a systemic treatment?

 

N acetyl glucosamine has always been of particular interest to me, as I've wondered if it couldn't be an important substance in blocking the antibody attack that seems to be taking place. There is some info here that I would really luv your take on, since it appears to be the strep reactive epitope and it has been found to block T cell reactivity. Now I'm looking at chitobiose in the IgG, and trying to figure out how that fits in the picture.

 

http://www.latitudes.org/forums/index.php?...etylglucosamine

 

I would be taking this in a heart beat, if I could find a product that I trusted for purity. I'm hesitant as I feel it would probably require a fairly decent amt.

 

 

Wendy,

 

Remember my level of knowledge here (minimal!) but it sure seems like it this could be playing a part. Please let us know if this is of any interest to Romy's Dr. and what his take on it is.

 

I know how frustrating it is to feel that you're really on to something and not have anyone who is on the same page. It's hard when there are so many idea's with some common end points, but different paths leading there. The way all 3 of the boys were affected seems to say something really important and I hope their story catches someone's interest. Hang in there. Maybe collectively, we'll make a difference here one way or another some day.