Anti-Lysoganglioside, Dopamine1 & 2 etc

[dcmom]

nevergiveup- Is your daughter on antibiotics? If so, what type and dosage?

[Buster]

When our kids immune systems over react and produce these antibodies that Cunningham has isolated and tested for, what made her look for these specific four antibodies???

Cunningham was looking at heart disease (carditis) and Kawasaki's disease. You can consider that she came at PANDAS from the Acute Rheumatic Fever space. Back in 1988, she published: http://www.ncbi.nlm.nih.gov/pubmed/3049816...p;ordinalpos=49

 

Are they anti strep antibodies? (All four). Why four different antibodies?

In a sense, yes. The way the immune system works is that a macrophage engulfs a bacteria and then tries to find a "key" on the bacteria that is like a signature. In the case of PANDAS, it looks like the "key" used is a particular sequence of a carbohydrate on the cell wall of the bacteria known as GlcNAc. Now the macrophage runs into a T-cell and says "there's bacteria out there and it has a signature of 'GlcNAc'". If there's enough macrophages/T-cells, then some of these will connect with some activated B-cells (B-cells make antibodies). When macrophages run into a B-cell and say "there's more bacteria out there go send out scouts (antibodies)". The B-cells connect up with the activated T-cells and thus the "signal" is confirmed by two parties (i.e., both the B-cell and a T-cell found it) so the B-cell makes anitbodies targeting the key sequence.

 

Just to make this clear, all sorts of keys are created when a Macrophage tries to find the "right sequence". Think of it as the macrophage is telling you the description of the bacteria but can only speak in DNA fragments. One says "it's got this carbohydrate sequence" another says "hey it has this protein sequence" and another finds yet another carbohydrate, .... There are thousands (possibly millions) of these "keys" on the edge of the bacteria.

 

Each macrophage has to chose one key to present as their "identification of the bacteria". Thus the more macrophages, the more keys get presented and the better the chance that one of them is accurate as a real key for the bacteria. Anyway, if enough of the Macrophages presents the same sequence on the exterior, this turns into a memory B-cell and then the memory B-cell produces antibodies to that particular sequence.

 

Now in the case of the four antibodies, Kirvan and Cunningham were looking at anti-lysogangliosides (meaning those antibodies that interfere with the bonding of lysogangliosides with neuronal tissue). They then isolated the bound antibodies and isolated four specific antibodies (one of which is known as 24.3.1). The point here is that there easily could be another 100 different antibodies also produced along with the anti-lysogangliosides. It just isn't known if the ones they isolated are the actual culprits. There is good evidence that 24.3.1 is the guy causing CaM Kinase II activation (i.e., opening of the Calcium channel). But whether it's leading to the wacky Basal Ganglia oddity, we don't know.

 

My previous neurologist whom doesn't believe in PANDAS but does think TS and OCD can be an autoimmune response once told me 5 years ago that different antibodies cause tics versus ocd?

I think that is true, but don't know.

 

If so does strep trigger different antibody production?

Yes. Although there may be other things that the B-cell recognizes and creates the faulty antibody for. Remember it is anything that presents the GlcNAc sequence (i.e., key) -- so if another bacteria has the same sequence then the B-cell will produce the same antibody. They aren't smart.

 

her Dop 2 is now elevated.

I don't think there is an elevated Dop 2 -- all ranges on the test are currently treated as normal.

 

Buster

[sf_mom]

Not a scientist... just a mother.

 

Is it possible underlying infection was not fully eradicated after initial IVIG and numbers are climbing because donor antibodies are effectively used up? Have you thought of trying a high dose antibiotic for a period of time?

 

-Wendy

 

 

Looking for feedback from Mommd and Buster and all other scientists. When our kids immune systems over react and produce these antibodies that Cunningham has isolated and tested for, what made her look for these specific four antibodies??? Are they anti strep antibodies? (All four). Why four different antibodies? My previous neurologist whom doesn't believe in PANDAS but does think TS and OCD can be an autoimmune response once told me 5 years ago that different antibodies cause tics versus ocd? If so does strep trigger different antibody production? My daughters ANA is so high and after IVIG her ANA was way down, but now her Cam Kinase is rising again 6 months after IVIG, and her Dop 2 is now elevated. (After IVIG it was within normal limits). She has asked for another IVIG, (she was sick for weeks after first IVIG). She knows things are getting worse again. Once the immune system is trained to produce these antibodies isn't it going to be hard to shut them off. Like in Lupus, MS and Chrons. My daughter has not been exposed to strep since her IVIG in May. She has had a slow worsening of symptoms over the last three months.

 

Any feedback? Thanks

[EAMom]

nevergiveup,

Yes...I also wonder about what antibiotic and dose your dd has been getting (how much does she weigh)?

 

Also, have you checked family members (throat cultures) recently to check for assymptomatic carriers?

[peglem]

This may be a stupid question, but I'm not proud. How do we know that none of the IVIG donor antibodies are not flakey PANDAS antibodies?

[Buster]

This may be a stupid question, but I'm not proud. How do we know that none of the IVIG donor antibodies are not flakey PANDAS antibodies?

We don't. But it seems given effectiveness of IVIG, it looks like the other antibodies from other parties are taking out the anti-host antibodies.

[nevergiveup]

Thanks for the response Buster. Her latest blood draw from Cunninham last week came with a range of normal for the antibodies. A little different than presented to me in August from Kathy.

 

Thanks to everyone for inquiring about her antibiotics. She has been on azith 250 per day since IVIG in May. We even had our dog on antibiotics to insure no family contamination. We swiched 3 weeks ago to AugmentinXR 1700 mg per day, she weighs 75 lbs. She always had low IGG IGM's for the previous 3 years. After her IVIG by Dr. L her IGG's dropped again and Immun docs agreed she has CVID. She starts her monthly IVIG's Wednesday. Only half the dose, she received in May but monthly. I am guessing with low IGG's if she has an infection maybe she cannot iradicate it. But most likely she has an autoimmune disease, overproducing strep antibodies and her body cannot turn it off. I can only hope these monthly IVIG work. I am concerned that we are downloading some of these antibodies into her with IVIG. I want to better understand the auto antibodies. Has anyone ever gone on gammagards web site. CVID has an autoimmune component plus low IGG and IGM's. No doctor ever explained any of this to me. Plus joint swelling, gastro problems, it sounds like all the PANDAS kids. Anyone trying to see an immun doc should read this web site.

 

Any advise welcome. My daughter had one severe attack at 9 and a second at 13. Her first attack lasted severe for one and half years. She was better for more than a year and had a second overnight attack in May. Although after IVIG I felt it didn't work, my daughter said in August and September that she had never been better in her life. She said she was quietly suffering from intrusive thoughts even when I felt she was in remission for years. She says IVIG got rid of them for the first time in 4 years.

 

Do you think with CVID she cannot fight the strep with high dose abx or is her immune system on auto without strep?

[Buster]

Do you think with CVID she cannot fight the strep with high dose abx or is her immune system on auto without strep?

 

For CVID, the typical problem is that the child gets lots of illnesses and their immune system is insufficient to fight off even most bacteria or viral infections. The monthly IVIG is to ensure there is an immune system capable of responding. The dosing of IVIG is tricky here and I'm not sure it is exactly known how much is necessary to augment an existing (but incompetent) immune system.

 

Was your daughter sick all the time with all sorts of diseases and having difficulty clearing the infections/illnesses? I remember way back the doctors thinking your child had childhood lupus.

 

With respect to the high dose abx, what makes sense to me is that it's helping the immune system get rid of a lingering gram positive infection. If the immune system is really terrible, then just having high dose antibiotics by themselves are probably not enough. The high dose probably only helps those that can mount an immune response of some form, but the immune response is just not enough for clearing the infection. For those with an incompetent immune system, the "borrowed" IVIG antibodies can at least help to wipe out antigens (with or without the antibiotics).

 

Antibodies tend to have a half life of 4-6 weeks, so dosing every 4 weeks will create a roughly stable immune system.

 

I totally understand your concerns on blood products and we have that same concern... but if the alternative is severe CVID there's not many other options.

 

Wishing you the best,

 

Buster

[kcdc3]

I wonder if anyone else who has a child with tics as the main, could let us know if they also had high lyso (and hi cam k s well....we were 179, which I find surprising, since some here with way more debilitating OCD have had a lower score than us).

 

 

Faith

 

Faith:

I'm the one who started this thread, but I'll repost so you won't have to scroll back, but just responding to your question above. My dd(10)'s Anti-L (320 - top of normal); Anti-T (1000 - top of normal); Dop 1 (2000 - top of normal); Dop 2 (8000 - middle of normal); CAM 163.

DD's main symptom (and was main symptom at time of blood draw) is a vocal tic. The vocal tic accompanies compulsions as well as she has the vocal tic just sitting watching TV. I would say her OCD is mild right now with her tics being almost constant. Of course, we go from mild OCD to full blown OCD with any exposure to illness. Tics also increase in volume (and frequency) for a week or so after exposure to illness, then calm down to a soft vocal tic.

[nevergiveup]

Buster,

 

Yep she was constantly struggling with sinus, respiratory, ear, cosackie, (several times) from age 3 on. Every three weeks she was ill for years. Her ped always tested her IGG's yearly from age 4 on, all were normal. Not untill her first PANDAS or SC attack at age 9, did she finally have a super high ANA 1:2560 and low IGG's, low IGM's and a very low C4. Yep lupus was on the table, still under review by doctors. But looks like not. (Thank goodness) My d has an autoimmune illness but the interesting thing is she has never tested high for Strep titer or antidnase titers. She was tested pretty consistently over the last several years for strep titers and they all came back on the low side. (At least 5 times). Does that mean she can't mount a response against strep?

 

What is the difference between strep titers and Cunninham's antibodies? When immune docs look at selective antibody def they look for low titers for specific illness. We always talk about high strep titers, what about very low or non existent titers for strep? Would't that also mean something?

 

My d will get 500 mg per kg or 15 grams every 4 weeks starting this week. They are giving her gammagard SD to prevent headaches, she was in serious pain after her first IVIG in May. I hope the monthly infusions help. It definately helped with OCD, allergies and her overall fatigue and chronic illness this summer. We are hopeful. Thanks

[faith]

So far it doesn't look like all tic presenters have high anti lyso...........

 

maybe it doesn't necessarily mean anything in particular,..

[faith]

What is the difference between strep titers and Cunninham's antibodies? When immune docs look at selective antibody def they look for low titers for specific illness. We always talk about high strep titers, what about very low or non existent titers for strep? Would't that also mean something?

 

 

ooh, that's an interesting theory, nevergivup,.....hmmm,...

 

 

Faith

[peglem]

This is kind of a conundrum. I thought that perhaps my daughter's low ASO, AntiDnase, in the face of confirmed strep might mean an immune deficiency...but then, if she's not making antibodies, then how could she have PANDAS?

[faith]

This is kind of a conundrum. I thought that perhaps my daughter's low ASO, AntiDnase, in the face of confirmed strep might mean an immune deficiency...but then, if she's not making antibodies, then how could she have PANDAS?

 

.............hmmm,

 

.......I got nothing.........

 

 

Faith

[peglem]

Well, but what if the strep is not producing much streptolysin? My daughter has pretty much been declared a carrier...she doesn't show any signs of infection, yet she has plenty of positive strep swabs that match up with behavioral flairs. My understanding is that streptolysin o is an enzyme produced by the strep to facilitates its attack on body tissue. So, if the strep isn't infecting, does that mean its not producing So?