If autoimmune...is there really a "cure" or just remission

[eljomom]

Does anyone really become "cured" with pitand/pandas? Or are the kids really just in remission? Still not totally certain about how autoimmune diseases work, but thought once they started, they never really go away.

 

I have also read that there does not need to be an infection to have an autoimmune response----can autoimmune cells just keep circulating after illness is gone? Longer than just the half-life...simply because there is an autoimmune process going on? Can kids just harbor antibodies to the basal gangia?

 

When is it too late for "full recovery?" I remember reading something by Swedo saying that IVIG/PEX generally only effective treatement option with initial onset episode.....

 

Are repeated illnesses without treatment more likely to cause kids do develop a "new baseline"?

 

If the same process is going on regardless of the severity, why not treat sooner (if abx not working) rather than wait for it to get worse?

 

Do we need to address the autoimmune, the inflammation, or the infection? In some cases, where antibiotics work, then it is addressing the infection, and the antibodies die out, and kid gets better. But in other cases, abx aren't working, so then what? We are left with no infection, but an autoimmune process?

 

How can you increase the function of Treg cells?

 

How can you decrease infllam. cytokines?

 

How do you get rid of autoantibodies? Close BBB?

 

I still believe this statement I thought of: I really believe there are 2 types of pitand/panda kids. #1 responds to antibiotics (maybe caught early) because antibiotics shut down the bacteria, and the antibodies eventually die out, and the exacerbation resides. #2 continues to have symptoms (even after virus/bacteria) is gone because it has gone on so long with repeated infections and no treatment, so the antibodies continue to go after self-tissue in the basal ganglia, and at this point the antibiotics are not going to be much help (other than maybe some anti-inflam. or immun-modulating). With the Cam K now being found to be high in "normal" kids with active strep, I would think Cam K would be better at identifying and treating kid #1, above, and the anti-neuronal antibodies might then be a better tool for kid #2, who continues to have symptoms beyond the normal "abx clears illness....antibodies die off", because these anti-neuronal antibodies indicate that there is truly auto-immune problem going on.

 

That may all be totally wrong, but am curious. And even if it is true, THEN WHAT?

 

I am sad. The one gift my dd was given has been taken away....her ability to draw. She told me the other day that she "can't draw good anymore" and asked if she is "still an artist."

[Guest pandas16]

I’m not sure how valid my answer will be because I have PANDAS. I know that I’m sometimes biased towards thinking more positively because I simply don’t want to believe all the negative things that could happen to me. However, I will try and answer your questions as best as I can based on my experience with the disease and the visits that I’ve had with doctors. As far I curing PANDAS, I don’t believe that it is possible at the moment. PANDAS was explained to me as a form of molecular mimicry- meaning my body thinks that my basal ganglia is strep and therefore it will always produce antibodies against it. Now, in absence of a strep infection this mechanism doesn’t present a problem because the blood brain barrier which protects the brain stays intact and the antibodies aren’t able to impair neurological functioning. In comparison, with an active strep infection not only would there be an enormous increase in anti-brain antibodies, but also cytokines, chemokines and macrophages which weaken the blood brain barrier. I know that B-Cells remember which is why continuous IVIG, PEX and steroids aren’t a “cure.” They only temporarily shut down the production of bad antibodies which allows the inflammation to go down. If strep comes back the body will remember how it reacted the first time when PANDAS started and result in the same phenomenon. I think hypothetically something like a stem cell transplant or bone marrow transplant which totally wipes out B-cell memory and reboots the immune system could be a cure, but that has yet to be explored.

 

I think the rule of thumb is to always address the infection first because that is what increases B-cells, macrophages and cytokines. If the infection is cured, the inflammation in the body SHOULD technically go down which is key in any autoimmune disease. I think whether or not kids need immunosuppressive therapy just depends on how severe the attack on their body was, how quickly the infection was dealt with, if they have immune deficiencies, how sick they were before the attack. Etc (A lot of different factors)

 

How can you increase the function of Treg cells?

I know that probiotics are supposed to increase the function of T-Reg cells, however they also stimulate the production of pro-inflammatory cytokines. The article below is on Chron’s disease but I think it can apply to PANDAS. It’s very interesting!

 

 

Even though the mechanisms of action of probiotics are still largely unknown and a matter of speculation, several lines of laboratory-generated evidence support their protective role in intestinal inflammation.

Probiotics have been shown to be effective against enteric pathogens by several mechanisms. They produce bacteriocins, a diverse group of low-molecular-weight peptides produced mostly by Lactobacillithat possess antimicrobial action against a number of bacteria, especially Gram-positive bacteria (reviewed in [5–7]). Similar substances, active against both Gram-positive and -negative bacteria, are also produced by Bifidobacteria.[8] In addition,Lactobacilli and Bifidobacteria are able to reduce the intracolonic pH by producing organic acids such as butyrate, lactic acid and propionic acid, thus creating an acidic pH milieu that is detrimental to the survival of several enteric pathogens, including Salmonella.[9]

One of the earliest findings in examining the actions of probiotics was their ability to prevent the attachment of pathogens to the enterocytes and to even displace bound pathogens from their binding site. These characteristics were shown to be possessed, to various degrees, by many of the commercially available probiotics.[10]

However, arguably the most important attribute that makes probiotics appealing for use in IBD is their ability to regulate the host mucosal immune response. Since it became known that immune as well as epithelial cells of the small intestine can discriminate between various microorganisms through the activation of Toll-like receptors (TLRs),[11] it was postulated that probiotics may act by modulating both the innate and adaptive branch of immunity, as well as the epithelial function in the small intestine. In fact, probiotics may affect barrier function by interacting with TLRs, in particular TLR2 and TLR4.[12,13] Interaction with these receptors results in the subsequent stimulation of protective cytokine production: IL-6 and KC-1, both known to mediate epithelial cell regeneration and inhibit their apoptosis.

However, not all effects of probiotics on epithelial barrier integrity appear to be mediated via interaction with TLRs. Probiotics have also been shown to stimulate epithelial cells' health by promoting the integrity of the tight junctional barrier between enterocytes. This effect has been shown in numerous animal models and in relation to a variety of agents causing the disruption of tight junction function. Examples include:

• VSL#3 in a murine model of colitis [14]

• Lactobacillus GG (LGG) in CaCO2 cell monolayers on the hydrogen peroxide-induced disruption of tight junctions and barrier function [15]

• Lactobacillus rhamnosus and Lactobacillus acidophilus in Shigella dysenteriae infection in rats [16]

• Bifidobacterium infantis in IL-10-deficient mice [17]

• Strains of Bifidobacterium lactis and Lactobacillus salivarius in CaCO2 cells challenged by Escherichia coli O157:H7 [18,19]

• B. lactis and Lactobacillus fermentum in CaCO2 cells against the damage induced by gliadin [19]

• E. coli Nissle 1917 in T84 cells challenged with enteropathogenic E. coli (EPEC) strain E2348/69 [20]

• The heat-killed L. acidophilus strain LB in HT cells [21]

Furthermore, Dalmasso et al. showed in an animal model of IBD that the probiotic yeast Saccharomyces boulardiihas a unique action on inflammation by a specific alteration of the migratory behavior of T cells, which accumulate in mesenteric lymph nodes.[22] In that setting, S. boulardii treatment limited both the infiltration of Th1 cells in the inflamed colon and the amplification of inflammation induced by proinflammatory cytokine production.

As reviewed in [23], probiotics can be internalized by the M cells and then interact with dendritic cells to activate both T- and B-cell responses. As a result, anti-inflammatory cytokines, including IL-10, are produced.[12,13] In addition, probiotics reduce the inflammatory response elicited by bacteria or other inflammatory stimuli by suppressing the production of proinflammatory cytokines. This effect has been shown in different animal models and for various strains, including LGG,[24] Lactobacillus caseiShirota,[25] E. coli Nissle 1917[26] and, directly in patients with IBD, for L. caseiDN114-01[27] and the patented probiotic preparation VSL#3.[28]

In our laboratory, LGG was able to prevent the fall in transepithelial resistance in an in vitro monolayer system of CaCO2 cells, caused by an E. coli strain (CD1033) identified from cultures of biopsies from the terminal ileum of children with Crohn's disease [Khaled Z et al., Manuscript in Preparation]. We proved this effect to be related to a derangement of the tight junction barrier induced by a reduction of the expression of the zonula occludens (ZO)-1 protein. Similarly, Zyrek et al. had shown that E. coli Nissle 1917 prevents the disruptive effects of EPEC on T84 epithelial cell monolayers by altering protein kinase C signaling and causing the redistribution of ZO-2 proteins.[20]

Vanderpool et al.recently reviewed mechanisms of probiotic action that may be involved in controlling intestinal inflammation.[29]

To summarize, it can therefore be seen that we have quite an extensive documentation of effects, which probiotics exert both in vivo and in vitro, that may be considered as useful in treating IBD patients as follows:

• Maintenance of the intestinal microbial balance in the presence of potential threats by pathogens;

• Regulation of the host mucosal immune function by inhibiting proinflammatory stimuli and enhancing the anti-inflammatory response;

• Protection of the integrity of the gut mucosal barrier by a variety of stimuli known to disrupt it.

I also just recently found a product called Moducare that I’m thinking about trying it. It doesn’t stimulate the immune system, it balances it. I haven’t tried it yet though. I’m going to an adult rheum soon and was planning on asking him about it.

 

How can you decrease inflammation and cytokines?

Definitely check for allergies and co-infections. For me, the 2 main things that cause me problems are allergies and hormones (estrogen). I use flaxseed oil to balance my hormones. I use Vitamin E to reduce glutamate toxicity and I use turmeric to control cytokine levels. I’m still looking for a probiotic that I don’t react to. During allergy season I use Nasonex and Zyrtec, but I’m thinking about trying Xolair which actually reduces the IgE antibody. (I have asthma too) It looks really good and gets at the root problem, but who knows. When I talk to my adult rheumatologist I was also going to ask him if a JAK inhibitor would work for PANDAS. There are a couple new ones that should receive FDA approval soon.

 

How do you get rid of auto antibodies? Close BBB?

I believe that with an autoimmune disease, you cannot ever completely rid the body of auto antibodies because B-Cells remember. In kids with PANDAS, the body thinks the brain is strep and will therefore always produce antibodies against the brain due to molecular mimicry. The body thinks there’s an active infection when there is not. I think PEX, IVIG, and steroids allow the body to get rid of antibodies temporarily which in turns allows the body to heal, the inflammation to go down and the blood brain barrier to become stronger. I don’t think they ever go away though.

 

Are repeated illnesses without treatment more likely to cause kids do develop a "new baseline"?

This is a very interesting question. After I was originally treated, I was more or less symptom free. When I would get sick, during certain times of my menstrual cycle, and during allergy season my symptoms would increase, but then go right back down to normal- meaning 0. In college however, I had several sinus infections as well as a documented Mycoplasma infection. After the Mycoplasma infection my symptoms increased and stayed at sort of a “high normal” level. I would say that I went down to 90% and didn’t go back up. I can still function just fine, but it’s “there,” whereas before it was not. Doctors have told me that Mycoplasma does not cross react with strep but I have read differently and I know how I feel. In the past I always went right back to 0 symptoms but not after Mycoplasma. THIS IS A TOTAL GUESS but I think if a virus or bacteria “cross reacts” with strep, antibodies will increase and IVIG, PEX, Steroids ect will be needed. I think if it’s a bacteria that doesn’t cross react, pro- inflammatory cytokines will increase temporarily and symptoms will go back to 0. Does anyone else agree with me on this? This is what I’ve experienced.

 

I’m 23 and hoping to get steroids soon. If I don’t go back to 0 symptoms, then I guess this is evidence that even with early diagnosis and proper treatment PANDAS can result in a permanent psychiatric disorder. If I can manage a complete recovery, I guess its evidence that it may not result in that. I will keep you posted.

 

As far as when is too late, I don’t know and it’s such a scary question. I think if PANDAS interferes with normal cognitive development, then it will certainly be more difficult. I was diagnosed when I was ten years old, so I had 10 years of “normal learned behavior.” I already knew what was appropriate and inappropriate. Plus my parents already knew that I was a normal functioning child before PANDAS. As a baby, it’s impossible to know. I do wish PANDAS was more black and white, but it seems to be a very complicated disease. I hope my answer helps you.

Edited February 5, 2011 by pandas16