Explaining IVIG to family

[bronxmom2]

Yes, Buster, thank you! You have a real talent for making this understandable. Is your daughter still doing well?

 

Did you consciously choose IVIG over PEX?

 

In your opinion, if you have a child with no primary immune deficiency, who has probably has probably been afflicted with these antibodies/inflammation for 4 years; whose symptoms are behavioral-- extreme obsessiveness and impulsivity, hyperactivity, ADHD, and anxiety-- and seem to be deepening month by month... which would be a better choice? Is PEX more... direct somehow, because it actually removes the antibodies? Is there some reason to believe that PEX could be more permanent?

 

Again, thank you!

 

Oh, and by the way... cam kinese of 160, anti-lyso... antineuronal antibodies 640 (4 times control)

 

How do you know if the T Cells (#2) are involved?

[Buster]

Hi Bronxmom2, yes our dd9 is doing great now 10 weeks post-IVIG. We had a hard first 2 weeks and then everything settled out in week 4 and it's been great since then -- I can't tell you what a relief this has been and both EAMom and I needed some quiet time to recover.

 

Did you consciously choose IVIG over PEX?

 

Yes we did. This was by no means an easy choice. PEX had the advantage of what appeared to be immediate results whereas IVIG was looking like 4-6 weeks before we'd see results. Swedo tended to use PEX for tic-primary disorders and IVIG for OCD-primary disorders. Our daughter's symptoms were primarily OCD and the secondary movement disorders seemed more OCD/chorea than a tic. Our biggest concern with IVIG was that we might be introducing some illness that is not yet tested and this haunted me personally and made me want to exhaust the other options before proceeding. The first 2 weeks post IVIG were torturous for I worried we had not only opened the possibility for a blood born illness, but also all her symptoms were coming back. Thank goodness for rock solid EAMom -- it was critically important that we were aligned on what to do so as to be supportive post IVIG.

 

In your opinion, if you have a child with no primary immune deficiency, who has probably has probably been afflicted with these antibodies/inflammation for 4 years; whose symptoms are behavioral-- extreme obsessiveness and impulsivity, hyperactivity, ADHD, and anxiety-- and seem to be deepening month by month... which would be a better choice? Is PEX more... direct somehow, because it actually removes the antibodies? Is there some reason to believe that PEX could be more permanent?

In my opinion, there is no reason to believe that PEX will be more permanent. Perhaps the critical item to consider is that the half-life (also known as the turnover rate) of antibodies is around 4-6 weeks (yes, it varies by antibody, but this is likely close). So, with PEX you'd have to be darn sure that you got rid of the original strep infection otherwise the antibodies will just come back. With IVIG, you actually are likely to get some "correct" antibodies to strep (meaning 1 in the 10000 donors probably have such antibodies) and thus these antibodies actually can take out remaining strep. Second with IVIG, there is some research (Kessel's paper for example) that the inrush of foreign antibodies reset T-reg cells. While this is incredibly preliminary, it gives some rationale as to why IVIG might have longer term sustainable effect over PEX.

 

Now on the downside, we're counting in IVIG on the incoming antibodies (T-regs) recognizing the "faulty antibody" and taking it out. We just don't know how likely this is relative to the very concrete evidence from PEX at removing antibodies. So what you have is that IVIG has a probability of removing faulty antibodies and a possibility of resetting T-regs. PEX has a definite ability to remove the faulty antibodies and is unlikely to reset T-regs.

 

So with all of that and that my dd9's symptoms were more OCD -- we went with IVIG. I totally appreciate why mom_md went with PEX given the severity of their symptoms and the higher tic component. Both approaches seemed effective. No matter what it is incredibly stressful to decide on either course.

 

How do you know if the T Cells (#2) are involved?

 

Actually, it isn't the T-cells, but rather the T-regulatory cells. It may also be related to B-regulatory cells. We're pretty certain T-reg cells are involved because the antibody is targeting GlcNAc carbohydrate which is a host carbohydrate. T-regs would normally suppress this antibody, but for some reason aren't. There is research that high levels of dopamine seem to suppress T-regs -- so perhaps that is the connection. We don't know.

 

Regards,

 

Buster

[peglem]

I don't understand why both can't be done at the same time- remove the antibodies and give donor Ig's. Am I missing something?

[Buster]

Hi Peglem, I'd recommend against joining the two procedures unless the situation is truly life threatening.

 

I don't understand why both can't be done at the same time- remove the antibodies and give donor Ig's. Am I missing something?

 

I'm not sure how literally to take your question. If you did them at the exact same time, you'd take out all the IVIG you're putting in because the blood circulates around many times and the PEX is logically a dilution action -- i.e., you keep taking out more and more antibodies till you've probably gotten a lot of them. Typically 70% reduction is consider a great PEX response.

 

** EDIT/correction: dc_mom points out that this procedure is done using a doner plasma instead of albumin. It still has the same "dilution" effect. Apparently plasma exchange is used both for replacing with doner plasma and for replacing with albumin. **

 

If you meant, "why not do PEX and then immediately do IVIG" -- probably the answer is exhaustion -- you've essentially spent 7+ hours/day over typically 2 days for PEX and have all the complications that might be there and then are doing 7+ hours for 2 days for IVIG. I'd also imagine that the inrush of foreign antibodies in IVIG might have much more severe response if your own immune system isn't up to snuff to take out the foreign antibodies. There are folks who have done this (see http://ard.bmj.com/cgi/content/abstract/61/1/37) but this is typically reserved for life threatening situations where an immediate response is needed and then an attempt to control improper re-emergence of the faulty antibody.

 

Regards,

 

Buster

[peglem]

Hi Peglem, I'd recommend against joining the two procedures unless the situation is truly life threatening.

 

I don't understand why both can't be done at the same time- remove the antibodies and give donor Ig's. Am I missing something?

 

I'm not sure how literally to take your question. If you did them at the exact same time, you'd take out all the IVIG you're putting in because the blood circulates around many times and the PEX is logically a dilution action -- i.e., you keep taking out more and more antibodies till you've probably gotten a lot of them. Typically 70% reduction is consider a great PEX response.

 

If you meant, "why not do PEX and then immediately do IVIG" -- probably the answer is exhaustion -- you've essentially spent 7+ hours/day over typically 2 days for PEX and have all the complications that might be there and then are doing 7+ hours for 2 days for IVIG. I'd also imagine that the inrush of foreign antibodies in IVIG might have much more severe response if your own immune system isn't up to snuff to take out the foreign antibodies. There are folks who have done this (see http://ard.bmj.com/cgi/content/abstract/61/1/37) but this is typically reserved for life threatening situations where an immediate response is needed and then an attempt to control improper re-emergence of the faulty antibody.

 

Regards,

 

Buster

Thanks, Buster. You understood my question exactly, and now I understand! So, PEX depletes (or greatly reduces) IgG?

[Buster]

Thanks, Buster. You understood my question exactly, and now I understand! So, PEX depletes (or greatly reduces) IgG?

Yes, PEX depletes and dilutes IgG -- you essentially don't have much of the IgG subclasses at the end and then your body has to make more (typically from bone marrow).

[peglem]

Thanks, Buster. You understood my question exactly, and now I understand! So, PEX depletes (or greatly reduces) IgG?

Yes, PEX depletes and dilutes IgG -- you essentially don't have much of the IgG subclasses at the end and then your body has to make more (typically from bone marrow).

So, if your body is making "naughty" antibodies, you'll just start all over again?

[dcmom]

While I definately don't want to disagree with Buster

 

I just have two things to add:

 

If you research plasma exchange, there are actually three types. In one of those, the patient recieves some type of donor plasma product.

 

When I discussed the possible use of pex or IVIG with and experienced pandas neurologist (Dr T) he told me when he has been involved they have done both (at the time that was like a punch in the stomach to me- for some reason).

 

So, I don't think it is out of the question, and I wonder peglem if it would be worth exploring this option for your daughter considering how long she may have been dealing with pandas, in a pretty extreme way.

 

We are doing pex, and I struggle with wanting to also do IVIG (but am holding off due to the donor exposure)- and dd has always been very healthy- so am not concerned with immunity issues. I guess I am now thinking of following the pex with strong antibiotic doses for an indeterminate amt of time.

 

Buster, EAmom- I think your dd is on daily zith. Since IVIG, do you have any plans in the future of pulling back on that? If so can you elaborate.

[Buster]

So, if your body is making "naughty" antibodies, you'll just start all over again?

 

Sort of, but not quite. Unlike other auto-immune diseases, the antigens in PANDAS (and in Sydenham Chorea) are not the body itself -- but rather coming from an incorrect response to an external antigen. This means that in PANDAS and SC there isn't the feedback loop that is so debilitating in all other auto-immune diseases.

 

Think of it this way, in PANDAS your body is "allergic" to something that invaded the body (i.e., GABHS). In other auto-immune diseases, your body is "allergic" to itself. Yikes. In PANDAS, your body needs the presenting antigen (i.e., GABHS). Without the antigen, your body shouldn't be making the "naughty" antibodies. This seems to be born out by the Swedo, Kirvan and Cunningham tests and followups at 1 year.

 

This is, however, why the prophylatic antibiotics is so important -- i.e., to keep the amount of antigen (and corresponding antibodies) low.

 

It takes about 4-6 weeks for antibodies to dissipate so hopefully the antibiotics can keep any antibody production way down until they dissipate.

 

This is already a long response to your short question. If helpful, I could start a separate thread on what we know about the immune system and cover this in more detail.

 

Regards,

 

Buster

[peglem]

This is already a long response to your short question. If helpful, I could start a separate thread on what we know about the immune system and cover this in more detail.

 

Regards,

 

Buster

 

Please! I want so badly to understand! We've been having a heck of a time clearing my daughter of strep. Just when we think we have it licked, it pops back in for another visit! Her CamK activation was 242%...and that was not during exacerbation...so, I'm so worried that if I do manage to get either treatment, it'll come right back.

[Buster]

Hi dcmom,

 

While I definately don't want to disagree with Buster

 

You are quite right and I fell into the trap of using Plasma Exchange and Plasmapherisis interchangably. Disagree anytime .

 

Anyone know which PEX was used by Swedo in her studies? Was it Albumin or high-mix antibody doner plasma?

 

It is a dilution effect (even with additional donor) since on average, the blood circulates around the body about once a minute (assuming 1 beat/sec). As such, I guess they just keep running the "filter" until the theoretical concentration of host antibodies to new antibodies reaches some threshold.

 

The effect would be the same as having some PEX and some IVIG.

 

Buster, EAmom- I think your dd is on daily zith. Since IVIG, do you have any plans in the future of pulling back on that? If so can you elaborate.

 

Well, we're basically on the prophylaxis until she's 18 or until the research can explain more of what we're seeing (i.e., we're hoping the next decade will figure this out). We will likely return to a more narrow band antibiotic in 6 months or so but really, truly don't want to repeat the past year. What we like about azith is the long half-life. We'd sure be interested in a narrow band penicillin that has a > 3 day half-life.

 

Regards,

 

Buster

[Buster]

Her CamK activation was 242%...and that was not during exacerbation...so, I'm so worried that if I do manage to get either treatment, it'll come right back.

Wow! That's right up with ours during an exacerbation. What are you currently using for prophylaxis? Is she coming back culture positive? Are you confident that strep is actually out of her system?

[peglem]

Her CamK activation was 242%...and that was not during exacerbation...so, I'm so worried that if I do manage to get either treatment, it'll come right back.

Wow! That's right up with ours during an exacerbation. What are you currently using for prophylaxis? Is she coming back culture positive? Are you confident that strep is actually out of her system?

The last 6 weeks have been kinda crazy with the abx. She'd been on 250mg zith/day for 5 days- then 7 days off, for about 18months. Sept 1st, she had a positive rapid and was given 500mg/day for 5 days...when I reported that her OCD was still bad, she was given 500mg Keflex 2x/day, which was upped to 3x/day after 4 days, and a 5 day course of prednisone...2 days later she got sick with something (strep was neg), and prophylaxis was changed to 500mg of zith on M, W, F...we did this for only one week...she had dental work (I was told I could give the 500mg for 5 days straight w/ the dental work) and got very ill the next day. That was Wednesday of this week and she has been on 1000mg 2x/day augmentin since Wednesday. When the augmentin is finished(10 day course) we are supposed to go back to the 500 mg. zith/MWF.

[dcmom]

So what type of dosing do you consider prophylactic? My dd is supposed to be on zith 2x week, 200mg each dose. I don't know if that is enough, and I have lots of rx so I am doing 200mg day for now. (she is 36lbs).

 

I like the zithromax if we can get down to a few times per week, because I think it is easier on the tummy. I had this conversation with Dr T and infectious disease dr at Gtown, and they think it may be better for the gut to get zith 2x week, rather than something every day like amox.

[EAMom]

peglem...how much does your dd weigh? Our dd (now 54 pounds) has been on 250mg Azith/day since June 08.