Anti-Lysoganglioside, Dopamine1 & 2 etc

[Buster]

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.

 

Yikes. Was her C8/C4 ratio also off the charts?

 

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?

No it doesn't mean that. The strep titers are measures of a response to two exotoxins of strep (so it isn't really a titer against strep but rather a titer against something that strep produces). About 46% of kids do not mount an ASO response even in the face of positive throat cultures. Was she positive on a throat culture each time (or the month before) she had the titers taken?

 

If she didn't have a positive culture 4-8 weeks before the titers were drawn it would be unlikely they would be elevated.

 

What is the difference between strep titers and Cunninham's antibodies?

 

Well, usually when folks use the term strep titers, they mean ASO or Anti-DNAseB which test for the presence of the exotoxins Streptolysin-O and Deoxyribonuclease B. There are lots of antibodies created to strep and to the exotoxins of strep. The two above are just the most common commercially available tests -- despite a high false negative rate.

 

The Cunningham antibodies are targeting a particular carbohydrate on the strep itself (known as GlcNAc). So the Cunningham antibodies have nothing to do with the ASO or Anti-DNAse B at all.

 

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?

Well, that's a bit tricky. Almost all titers are checks after an exposure -- for example, typically an immunologist is looking for a 4-10 fold increase in antibodies after a vaccination. The baseline titers may have meaning, but all studies I've seen look at titer responses after a challenge. Thus the difficulty with strep is that until the strep enters the blood stream (i.e., not on the skin or throat but an actual invasion like a shot) then there probably won't be a rise in titers.

 

In terms of abnormally low titers, as far as I know it hasn't been studied. Even Ed Kaplan has said that 'carrier state' is likely much less benign than originally thought.

 

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.

Did you use Gammunex 10% before? We had very good results with that because of the low sucrous level.

 

Buster

[Buster]

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?

 

Okay, deep breath, ....

 

The antibody that is thought to cause PANDAS is NOT ASO or AntiDNase-B. These antibodies do not rise in over 37% of patients with streptococcal infections -- i.e. in more than a third of kids, the ASO and AntiDNAse-B measures are meaningless.

 

The antibody that is thought to cause PANDAS is targeting a carbohydrate on the cell wall of GABHS. This antibody response can happen even if there is only a mild infection or mild invasion for children who's immune system is hyper-sensitized to GABHS (the bacteria). The PANDAS antibody can activate even if ASO and Anti-DNAse B don't.

 

If you are wondering why Singer, Kurlan, Kaplan and the crew all focus so closely on ASO and Anti-DNAse B is that they basically have no other method to have a "definite" strep infection. So all their studies are about "definite" infections, they haven't bothered yet to test "probable". Oh, I could go on and on about sampling theory problems here....but let me just keep it simple, the Kirvan studies matter because they've found a differnet antibody that seems to rise in those with SC and PANDAS -- regardless of ASO titers when the PANDAS/SC child is exposed to GABHS.

 

Regards,

 

Buster

[Buster]

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?

Streptolysin-O is neutralized by cholestrol. This is why if you have a skin infection you generally won't have any ASO rise. In addition, in many with carrier state GABHS, it appears that several of the exotoxins are disabled and several of the proteins (such as M1) are also disabled. It is not known why this happens for carriers.

 

Buster

[coco]

Buster, you bring up a very interesting point...do you have any other thoughts regarding IVIG dosage amount? Swedo recommended 2.0 grams over 2 days, Dr. K does 1.75 grams over 2 days...now, my dd immuno is giving 200 mgs monthly, as she has SAID in addition to Pandas. My husband and I question the dosage, is it enough? After we did IVIG with Dr. K. 6 weeks post we had her pneumo strep 14 strain tested, as her immuno told us it would give us an idea how quickly she is going through the gamma. She still failed 13 of 14 serotypes, some only slightly better, others worse than prior ivig. I was thinking of asking Dr. to up the gamma...any thoughts on that? Does anyone else know what their monthly ivig dosages are if their kids are receiving monthly treatments? Thanks so much!

 

Coco

[nevergiveup]

Buster, and Coco,

 

Thanks so much for this explanation. I really need to understand this stuff, so I can talk with the immun docs. Now I finally understand why my old neurologist ran these tests but never put much thought into them. (He works with Singer a lot, but hes also a statistic guy and would clearly understand this)

 

So I don't know the brand used at the hemoc center in Georgetown but it is not the Dr K brand for sure. My daughter could not have had any more than the 1 gram per kg because she was in lots of pain. Supposedly Gammagard SD (the stuff she is getting tomorrow) has no sucrose, I need to check again. But in a study against straight gammagard, headaches as a side effect were much less with the SD product. You have to special qualify by insurance (how sad they are always messing with our care) to get the SD, low IGA's I believe. But my daughter didn't have that so I am not sure yet why she got it, probably for the less side effects. As for the C8, they only ran 1 through 4 and then a different type of marker called C25, which was normal. I will ask about C8. Thanks.

 

Coco, usually IVIG's are prescribed by weight. So when you said 200 mg did you mean per kg if so then yes this is very low for SAID. I thought normal was 400, my doc is giving 500 because she wants the dose to help her PANDAS, also, not just CVID. I do not think she could do much higher than that every 4 weeks. She would be too sick from fatigue if she did a higher dose monthly. Aren't you with Bouboulis? My daughters pnemoccocal titers were much higher, passed almost all, 7 weeks post the PANDAS dose IVIG. Didn't last though, 12 weeks post they dropped off again. So it seems like a higher dose would help. Again check your dose it seems drastically low.

 

Thanks for all the advise.