Lesson learned

[Joan Pandas Mom]

Peg, I'm so sorry to hear things are down-sliding. You are such a great mom and doing everything you possibly can. Things are going to get better and stay better. Hang in there and keep up the good work.

[bronxmom2]

Peglem, the low dose (1.0) also made my son worse. Much worse.

 

He made a rapid recovery when he switched to Dr. K's protocol (1.5 over two days)

 

You really must push for the higher dose. Will you Dr. talk to Dr. K? Dr. K convinced Dr. B that PANDAS kids cannot be treated like regular immune-deficient kids and got him to change his procedure-- which I am so grateful for.

[Suzan]

Very sorry and sad to hear this especially as we move towards our low dose next week. I will see if our immunologist will call Dr. K. Please keep us posted and hang in there.

 

Susan

[trggirl]

Please keep us posted Peglem. I think it is very interesting information you found about LD IVIG causing inflammation. You may be onto something there.

[peglem]

Okay, pediatrician has called in rx for pred. Now I just need to convince the immuno to do a higher dose of IVIG. We'll see him on Monday. I haven't spoken to this one before. Would appreciate your prayers that it all works out, and research on ivig would be good, too.

[Megs_Mom]

Okay, pediatrician has called in rx for pred. Now I just need to convince the immuno to do a higher dose of IVIG. We'll see him on Monday. I haven't spoken to this one before. Would appreciate your prayers that it all works out, and research on ivig would be good, too.

Sending prayers your way. Good luck on Monday - at minimum, hope he will consult with Dr. K.

[marilina]

they talk about Kawasaky desease but I've found this:

 

http://www.childrensheartresearchguild.org...anspotlight.pdf

"There also seems to be a genetic reason why the IVIG does not work for all patients. When the IVIG is given to a patient, it binds to receptor cells, turning the inflammatory cells either on or off. However, there may be an abnormal or mutated receptor in the patients who do not respond to the IVIG, therefore preventing the IVIG from properly binding to the receptor cells. Dr. Portman is studying polymorphisms in genes, which are changes in the genetic sequence, and also single nucleotide polymorphisms - mutations at a single point.Clinical trials are currently underway to treat Kawasaki Disease using Etanercept (commonly known as Enbrel), a drug which is typically used in adults and children two years of age and older for inflammatory disease such as rheumatoid arthritis and psoriasis. In pilot trials combining the IVIG with the Enbrel, recurrence of inflammation was nonexistent. When giving patients only the IVIG, inflammation reoccurs in about 25% of patients. However, more data needs to be collected through a large multi-center trial."

[peglem]

Thank you Marilina! I found a few more abstracts (wish I could get full text) that are pertinent:

 

http://www.ncbi.nlm.nih.gov/pubmed/19883419

Clin Exp Immunol. 2009 Dec;158 Suppl 1:2-13.

Intravenous immunoglobulins--understanding properties and mechanisms.

 

Durandy A, Kaveri SV, Kuijpers TW, Basta M, Miescher S, Ravetch JV, Rieben R.

 

INSERM U768, Université Paris-Descartes, Hospital Necker, Paris, France.

Abstract

 

High-dose intravenous immunoglobulin (IVIg) preparations are used currently for the treatment of autoimmune or inflammatory diseases. Despite numerous studies demonstrating efficacy, the precise mode of action of IVIg remains unclear. Paradoxically, IgG can exert both pro- and anti-inflammatory activities, depending on its concentration. The proinflammatory activity of low-dose IVIg requires complement activation or binding of the Fc fragment of IgG to IgG-specific receptors (FcgammaR) on innate immune effector cells. In contrast, when administered in high concentrations, IVIg has anti-inflammatory properties. How this anti-inflammatory effect is mediated has not yet been elucidated fully, and several mutually non-exclusive mechanisms have been proposed. This paper represents the proceedings of a session entitled 'IVIg--Understanding properties and mechanisms' at the 6th International Immunoglobulin Symposium that was held in Interlaken on 26-28 March 2009. The presentations addressed how IgG may affect the cellular compartment, evidence for IVIg-mediated scavenging of complement fragments, the role of the dimeric fraction of IVIg, the anti-inflammatory properties of the minor fraction of sialylated IgG molecules, and the genetic organization and variation in FcgammaRs. These findings demonstrate the considerable progress that has been made in understanding the mechanisms of action of IVIgs, and may influence future perspectives in the field of Ig therapy.

 

PMID: 19883419 [PubMed - indexed for MEDLINE]

 

AND

http://www.ncbi.nlm.nih.gov/pubmed/18926775

Trends Immunol. 2008 Dec;29(12):608-15. Epub 2008 Oct 14.

Modulation of the cellular immune system by intravenous immunoglobulin.

 

Tha-In T, Bayry J, Metselaar HJ, Kaveri SV, Kwekkeboom J.

 

Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, the Netherlands.

Abstract

 

Intravenous immunoglobulin (IVIg) is therapeutically used in a variety of immune-mediated diseases. The beneficial effects of IVIg in auto-antibody-mediated diseases can be explained by neutralization, accelerated clearance and prevention of Fcgamma-receptor binding of auto-antibodies. However, the means by which IVIg exerts therapeutic effects in disorders mediated by cellular immunity have remained enigmatic. Clinical improvements, followed by IVIg treatment, often extend beyond the half-life of infused IgG, thereby indicating that IVIg modifies the cellular immune compartment for a prolonged period. Here, we discuss recent advances in the understanding of different, mutually non-exclusive mechanisms of action of IVIg on cells of the innate and adaptive immune system. These mechanisms might explain the beneficial effects of IVIg in certain autoimmune and inflammatory diseases.

 

PMID: 18926775 [PubMed - indexed for MEDLINE]

[kim]

Peglem,

 

I had an article saved that I think expands just a little on the abstract that you posted

 

Scientists ID a single sugar that allows antibodies to fight inflammation

 

http://newswire.rockefeller.edu/?id=513&page=engine

 

Because a therapeutic, anti-inflammatory response to IVIG requires a concentration of IgG antibodies that’s hundreds of times greater than is normally used for antibody therapy for cancer or infection, for example, Ravetch and his colleagues began to look for something that was only present in IVIG in small amounts. That’s how they discovered that just the very terminal sialic acid on the Fc portions of the IgG molecule were the root of the anti-inflammatory activity. When the researchers removed the sialic acid, the molecule retained its structure and its half-life, but it lost its protective abilities. “This is a very interesting condition that’s set up,” Ravetch says. “IgG can shift from a state that is quite inflammatory to a state that is actively anti-inflammatory by just changing a sugar.” This switch occurs during a normal immune response to a foreign substance, shifting the IgG antibodies from an anti-inflammatory state to one that is pro-inflammatory and able to efficiently dispose of the foreign challenge

 

This seems to beg the question of what are they trying to accomplish with IVIG? In Momto2's cases, she wants to clear an infection, would low dose be a better option?

 

From 2nd abstact above...this is the part I'm really curious about too

However, the means by which IVIg exerts therapeutic effects in disorders mediated by cellular immunity have remained enigmatic

. Edited April 23, 2010 by kim

[peglem]

Peglem,

 

I had an article saved that I think expands just a little on the abstract that you posted

 

 

http://newswire.rockefeller.edu/?id=513&page=engine

 

Because a therapeutic, anti-inflammatory response to IVIG requires a concentration of IgG antibodies that’s hundreds of times greater than is normally used for antibody therapy for cancer or infection, for example, Ravetch and his colleagues began to look for something that was only present in IVIG in small amounts. That’s how they discovered that just the very terminal sialic acid on the Fc portions of the IgG molecule were the root of the anti-inflammatory activity. When the researchers removed the sialic acid, the molecule retained its structure and its half-life, but it lost its protective abilities. “This is a very interesting condition that’s set up,” Ravetch says. “IgG can shift from a state that is quite inflammatory to a state that is actively anti-inflammatory by just changing a sugar.” This switch occurs during a normal immune response to a foreign substance, shifting the IgG antibodies from an anti-inflammatory state to one that is pro-inflammatory and able to efficiently dispose of the foreign challenge

.

 

Yes, I have this article (I think I cited it somewhere on the forum, but no matter). They are in the process of developing an IVIG product w/ increased levels of scialic acid that would be anti inflammatory at a lower dose.

[peglem]

and another:

http://www.ncbi.nlm.nih.gov/pmc/articles/P...16/?tool=pubmed

[peglem]

So saw the brother of the immunologist today. He's also an immunologist in the same office as Allie's. This was so easy! He said he read the report from Dr.L (she recommended 1gm/kg). But, he said, in reviewing the literature, he thinks that 1.5g/kg is the usual in the case of PANDAS. So, that's what he's ordering, over 2 days. I was all ready with my articles and information...didn't need it!

[EAMom]

So saw the brother of the immunologist today. He's also an immunologist in the same office as Allie's. This was so easy! He said he read the report from Dr.L (she recommended 1gm/kg). But, he said, in reviewing the literature, he thinks that 1.5g/kg is the usual in the case of PANDAS. So, that's what he's ordering, over 2 days. I was all ready with my articles and information...didn't need it!

 

Yay!!!!

[bronxmom2]

good job! I think you will see a difference at the dosage.

[peglem]

good job! I think you will see a difference at the dosage.

I'm still scared- turning back the pages....there are many pages in this book that I don't want to read again!

This guy wants us to do 2 of them a month apart, then check how its going.