Gbs/cidp Newsletter

I did sign up with the foundation as a CIDP person. They sent me a list of lots of people, names, and addresses. I actually got a call this passed Sunday from a very nice lady in South Dakota with CIDP. We talked about our symptoms and treatments…that was nice to be able to talk to someone.

I do get the newsletters, too.

I think it’s great. It really helps to get all the information that we can.

Stacey

MG,

I think a great many of the forum members have their names registered with the foundation and therefore receive the Communicator. There are hundreds of people out there who dont belong to the forums but are in the Foundation database. If you call the foundations, or send some kind of communication with regards to CIDP/GBS, they will enter you into the database and send you information and the newsletter. Imagine how wonderful it is for them to receive the latest news, especially if they arent able to join us on the forum for support.

Great point everyone here makes. If you are not on our mailing list please copy and paste the link below and fill out our contact form and information will be on the way. Thanks

[url]http://www.gbs-cidp.org/contactus.htm[/url]

-GBS/CIDP

Morning, all

I was so excited when I got my newsletter! 😀 All about CIDP. It had some great info for all of us. At the convention last year, there were a lot of attendees with CIDP — we had our own track at the conference.

Yes, I hope everyone belongs to the foundation — we need organizations like this to continue to push for research and treatments.

Cathy

[QUOTE=Miami Girl]
In today’s mail, I received my latest newsletter from the foundation ………….

Apparently, the researchers are onto something called FAS, which shuts down the system faster in GBS than in CIDP…they did studies to identify
this process and are looking into why it doesn’t shut down the immune system
faster in CIDP cases.
[/QUOTE]

I found the newsletter I just received in the mail very informative. The mention of FAS interested me, too. I couldn’t remember much about it so I pulled out my Immunology textbook back from when I audited the course before retiring.

In case anyone is interested, here is what I found: FAS is a surface protein receptor on target cells, which when activated causes target cell death. Tc cells (one of several kinds of T cells called cytotoxic T cells) reacting to a signal (for example an antigen) express something called FAS ligand which binds to FAS telling it to kill the target cell (apoptosis).

[QUOTE=Miami Girl]
Apparently, the researchers are onto something called FAS, which shuts down the system faster in GBS than in CIDP…they did studies to identify
this process and are looking into why it doesn’t shut down the immune system
faster in CIDP cases.
Miami Girl :cool:[/QUOTE]

Hi Miami Girl,

It has been well documented that GBS is a Th1 cell-mediated immune response to antigen. Most info I could find seemed to lump CIDP into that same group. I have always questioned this – partly because of the difference in the self-limiting factor, and also in the striking differences of onset. I believe that CIDP is a combination of Th1 (during the immediate onset of relapse), and then a shift to a Th2 antibody-mediated immune response (during the interval until the next upswing). It is this cyclical Th2 response that prevents a fas-mediated death of autoreactive cells that perpetuate CIDP. I am not a doctor or in the medical profession so this is just my theory, but here is a portion of a study on b-cell apoptosis that indirectly supports my theory (in relation to fas; there are lots of other processes involved):

An additional determinant of
the B cell’s fate may be the relative abundance
of Thl and Th2 cells in culture. Thl cells secrete cytokines
central to the cellular immune response, such as IL-2
and IFN-~/(40), and they selectively express Fas ligand after
activation (12), while CD4 + Th2 cells secrete cytokines
that support the humoral immune response. A role for
CD4 + Thl cells in Apo-1/Fas-mediated B cell death is
consistent with this functional dichotomy, and it supports a
mechansim other than antagonistic cytokine effects by
which Thl cells can downregulate B cell responses.

See also the thread by Dell’s mom titled “I wonder if your doctors should test for interleukin 2”.

Norb,

I think this article might interest you and others w/IgM/pdn/anti-mag. I think the article is primarily targeted at lymphoma and hyper IgM syndrome, but it discusses specific pathways to b-cell deletion. Here is the link to the above referenced article (pdf):

[url]http://www.jem.org/cgi/reprint/182/5/1557?ijkey=2496744f4535fa79b3ffe379cb5afcfff2cd5221[/url]

And another article – discussing a special fractionated ivig used in the laboratory to demonstrate fas-mediated apoptosis of b-cells.

[url]http://www.jimmunol.org/cgi/content/full/161/7/3781[/url]

cd

[QUOTE=norb]I found the newsletter I just received in the mail very informative. The mention of FAS interested me, too. I couldn’t remember much about it so I pulled out my Immunology textbook back from when I audited the course before retiring.

In case anyone is interested, here is what I found: FAS is a surface protein receptor on target cells, which when activated causes target cell death. Tc cells (one of several kinds of T cells called cytotoxic T cells) reacting to a signal (for example an antigen) express something called FAS ligand which binds to FAS telling it to kill the target cell (apoptosis).[/QUOTE]
Where can I get more info? Sounds interesting.Does the apoptosis stop the inflammatory
responce?

[QUOTE=joe flaherty]Where can I get more info? Sounds interesting.Does the apoptosis stop the inflammatory
responce?[/QUOTE]
Joe, google FAS or apoptosis, that might get you some info. A good source would be a paperback which I found very useful in understanding the immune system. Lots of diagrams. It has a chapter on autoimmune diseases. “Life, Death and the Immune System” a Scientific American special edition, 136 pages, W.H. Freeman and Co, New York. It is out of print but I’ve seen it used for around $5 at amazon.com. Some of it may be outdated and newer research is missing. But the basics have not changed.

Apoptosis simply means cell death. This could be any body cell or bacteria. Here is the way I understand the process – and I am no expert!!! If one active B cell (called plasma cell) that creates antibodies attacking myelin would die through apoptosis after its normal life cycle is over (4-5 days), any inflammation caused by it would stop. But there are probably many other anti-myelin B-cells being created as long as there is any myelin left to be attacked. So, inflammation would continue.

Here a PM with Miami Girl that might be of interest.

[B]Miami Girl[/B], I corrected the sentence before the last. I meant to say NK and not B cells.

[QUOTE=Miami Girl]Norb

I think that I might be on to something…folic acid is one of the vitamin B family…it’s forced on pregnant
women to help the immune system grow within the fetus.

Julie is taking it for a condition on the forum, so I did look it up…Foltx…read it…the folic acid in straight
form, lowers the killer cells…

Here’s the site…pamlab.com/products,foltx

Miami Girl[/QUOTE]

Hi,
interesting. I didn’t know that about folic acid. I’ll ask my daughter about it when she comes Sat to visit. She is a doc and pregnant wih her second child.

But.. I guess I am still confused. Why would I with antiMAG neuropathy want to lower NK cells. Wouldn’t I be shooting myself in the foot? I just went back to the GBS/CIDP newsletter which I haven’t followed the last few days and can’t remember all that has been said. You wrote there: “I found that the NK (natural killer) cells in our particular cases, run rampant and kill the good cells…what triggers this “overkill” remains the issue”. My problem is “bad” B-cells which refuse to die. I don’t know what the mechanism is by which they normally die as they should after 4-5 days of producing millions of “bad” antibodies. I don’t know whether the death normally is initiated by Tc cells (killer T cells using Fas) , NK (natural killer) cells , or if it happens from within the B-cells without outside “help”. Somebody is not “doing his job” and the damage to MAG/myelin continues. I also don’t know if B cells that “fit” the MAG sequence of protein continue to be created and only some of them don’t die or if it is one or more “bad” B-cell that decided to stick around forever by somehow avoiding Tc or NK cells and no additional ones are coming. Not knowing any of this, reducing the number of NK cells in my case would not be wise. They might actually keep the “bad” B-cells in check.

Take care

[QUOTE=Miami Girl]
I found that the NK (natural killer) cells in our particular cases, run rampant and kill the good cells…what triggers this “overkill” remains the issue. [/QUOTE]

I’ve been thinking about this some more last night and I question if this is correct. Where did you get that?

[QUOTE=Miami Girl]The T cells help the B cells fight the antibodies…so, if our T cells are part ofthe NK subform, then lowering them seems less likely that they will infiltrate
all cells. On the other hand, to stop them would also stop the process of fighting the antibodies…thus we are back to total immunosuppression …[/QUOTE]

1. [U]T cells do not help the B cells fight antibodies[/U]. NK cells are usually not considered T cells and do not “fight” antibodies either. Antibodies are not cells but complex molecules. T helper cells do just the opposite of fighting antibodies. Once activated by an antigen, T helper cells cause B cells with a corresponding cleft to muliply (polyclonal) and mature into plasma cells. Then each individual cell starts producing up to 72 million antibodies until it dies after 4-5 days. These antibodies have identical clefts that fit the antigen being targeted. In CIDP, of course, the antigen is the myelin.

These antibodies (usually IgG) attach to the myelin and NK (natural killer) cells attach to the antibodies initiating cell destruction. There are other mechanisms involved I don’t want to get into. I am not sure yet where the inflammation we get fits in.

Researchers in Japan found large amounts of NK cells on myelin lesions of CIDP patients.
(“Differential Expression of NK T Cell Va24JaQ Invariant TCR Chain in the Lesions of Multiple Sclerosis and Chronic
Inflammatory Demyelinating Polyneuropathy”)

NK cells make up 10-20% of white blood cells and represent an important component of our immune system. They do not attack normal healthy cells unless these are tagged for destruction like myelin. NK do not infiltrate cells.

[QUOTE]I read in an Oxford Journal, that in your particular issue with the IgM, most doctors don’t recommend treating the neuropathy as the patient gets older.
They don’t recommend any immune therapy because of the side effects.
It said that when a male reaches his sixth decade, immune therapy is not recommended. Your variant is very slow, mostly sensory and occurs mostly in men. [/QUOTE]

Some doctors do, I am aware of that. I’ve read the same, seem to be British doctors. Perhaps they belong to an older generation themselves or they suggest not to treat because newer treatments were not available or unknown to them. Today most others are recommending Rituxan for antiMAG as the most effective treatment for most patients with few side effects.

I’ve had this disease for six years now, cannot walk without walker, have a difficult time holding anything in my hands, typing is extremely difficult and takes 10 times as long as it used to. Symptoms keep getting worse. My feet have been totally numb for a couple of years. My hands lost most of their sensation, and since two or three weeks my tongue is getting increasingly numb. In addition to some minor ones, I had two very serious falls this year with one resulting in a huge subdural hematoma that pushed my left brain to the side and down. It went unnoticed for several weeks and almost cost me my life. I had a succesful brain surgery in March.
Don’t you think I deserve treatment even though I am 74 years old?

[QUOTE=Miami Girl]Norb

Of course you deserve any treatment that you can get…I was telling you what I had read. My comment was about your doctor making an age criteria to you.[/QUOTE]

Sorry, what I wrote was not directed to you. I was just venting to whoever was listening to me. 😮

[QUOTE]I just finished reading about the B cells are helped by the T cells. I have read so much in the last two weeks, it’s not funny. [/QUOTE]

I know what you mean. The immune system is so complicated it is very difficult to understand. I keep going back to my textbook all the time. There is another book I use a lot which is much easier to understand. I just mentioned it earlier here answering a post by Joe:

[QUOTE=Norb]A good source would be a paperback which I found very useful in understanding the immune system. Lots of diagrams. It has a chapter on autoimmune diseases. “Life, Death and the Immune System” a Scientific American special edition, 136 pages, W.H. Freeman and Co, New York. It is out of print but I’ve seen it used for around $5 at amazon.com. Some of it may be outdated and newer research is missing. But the basics have not changed. [/QUOTE]

On a related subject: You mentioned in another thread that a doc told you it was genetic but your DNA testing didn’t show any damage. There is one popular theory how some auto-immune diseases get started: It is called molecular mimicry in addition to a genetic predisposition. This is not a genetic flaw but a normal variation in the genetic code. If you are interested I’ll find my post where I gave an explanation of this plus a diagram.

[QUOTE=Miami Girl]I’m still looking for that abstract about the NK cells…I went into three screens
to see it, that much I remember.

Miami Girl[/QUOTE]

I started searching, too. Lots of pages but no luck yet.

What I did notice that many scientist call them NK T cell and not just NK cells. According to my text they could be considered [U]immature [/U]T cells. There is one basic difference between NK and regular T cells. NK cells lack T cell markers and therefore are not affected by the presence or absence of antigen. However, they mediate cytotoxicity against IgG coated target cells (myelin for example). This is called ADCC (antibody dependent cell-mediated cytotoxicity). Their presumed importance is as anti-tumor and anti-viral cells.

I put together a hypothetical timeline in relation to how Nk mediated IgM pathology is thought to occur; references are included that I based my model on.

Hope this helps to distinguish some of the differences between NK and NKT cells.

Cd

NK cells originate in the bone marrow. They can kill tumor and virus cells directly without receptor stimulation. In addition, by stimulation of receptors, NK cells produce cytokines that signal B-cells to produce antibodies.

NK ->
[normal response]
stimulate B-cells to produce antibodies (immunoglobulin response)->
immunoglobulin switching from IgM to IgG, IgA, IgE etc. specific to angtigen peptides ->
[immune dysfunction]
failure of Ig switching caused by cd40 receptor/ligand dysfunction in T-cells ->
results in high levels of IgM, low levels of IgG, etc ->
deposits of IgM & complement on nerve myelin

References:

pathological studies on nerve biopsies show segmental demyelination with deposits of IgM M-protein and complement on nerve myelin (Nemni et al., 1983Go; Vital et al., 1989Go; Hays et al., 1988Go; Monaco et al., 1990Go; Nobile-Orazio et al., 1994Go; Van den Berg et al., 1996Go);

[url]http://content.nejm.org/cgi/content/abstract/322/10/649[/url]
Complement-mediated demyelination in patients with IgM monoclonal gammopathy and polyneuropathy

[url]http://intimm.oxfordjournals.org/cgi/content/abstract/4/12/1373[/url]
Activation of B lymphocytes by NK cells

[url]http://www.ihop-net.org/UniPub/iHOP/pm/9107469.html?nr=1&pmid=11714772[/url]
Human B cell activation by autologous NK cells is regulated by CD40 -CD40 ligand interaction: role of memory B cells and CD5+ B cells.

* * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * *

NK T-cells originate in the thymus. NKT cells express an extremely limited T cell repertoire – their receptors almost exclusively target lipids, glycolipids, or other hydrophobic peptides presented by CD1D molecules.

J Immunol. 2006 Oct 15;177(8):5226-35.
Expression of CD1d molecules by human schwann cells and potential interactions with immunoregulatory invariant NK T cells.

[QUOTE=Miami Girl]Norb, Aren’t all T cells immature until they mature in the thymus, where they start to grow and then travel?
[/QUOTE]
Yes, that’s true. Actually, the text calls immature T cells pre-T cells. NK cells can be considered [B]primitive[/B] T cells not [B]immature [/B] ones like I said earlier. I could not find out what path they take during their development. It says that the lineage is controversial. One newer article I googled says: “[I]Natural killer (NK) cells are a distinct non-T, non-B lineage of lymphocytes [/I]”

In destroying tumor cells both T cells and NK cells work together. The T cells encounter the antigen on tumor cells and send out cytokines which activate NK cell precursors and cause them to proliferate and attack the tumor cell. Another process involves B cell antibodies which coat tumor cells and provide a handle for NK cells to attack.
[QUOTE] I’m still looking…this keeps me up quite late you know…I got up at 2:00 pm today…to some hungry cats…lol.[/QUOTE]:eek: I hope you don’t wear yourself out with all that theoretical immunity stuff.
[QUOTE] I literally, cringed when I read how you fell on your knee. That must have been excruciatingly painful.[/QUOTE] Yes, for weeks after I fractured my knee. I couldn’t do anything without help. Six weeks in a wheelchair helped me appreciate what it must be like for you and many others. I may be headed that way, too, and got an early taste of it.

[QUOTE=Miami Girl] I read about caspase and such…
Miami Girl[/QUOTE]
Interesting. One definion says
[QUOTE]Caspases are essential in cells for apoptosis, one of the main types of programmed cell death in development and most other stages of adult life, and have been termed “executioner” proteins for their roles in the cell. Some caspases are also required in the immune system for the maturation of cytokines. [U]Failure of apoptosis is one of the main contributions to tumour development and autoimmune diseases[/U]; this coupled with the unwanted apoptosis that occurs with ischaemia or Alzheimer’s disease, has boomed the [I]interest in caspases as potential therapeutic targets[/I] since they were discovered in the mid 1990s.[/QUOTE]

[B][/B]

[QUOTE=compactdisc]I put together a hypothetical timeline in relation to how Nk mediated IgM pathology is thought to occur.[/QUOTE]

I need some time to read up on this and digest it.

Thanks, CD, for researching this. I don’t believe that all of your model fits my situation. I have [COLOR=”Red”]antiMAG [/COLOR]IgM neuropathy. IgM does not coat myelin but [COLOR=”Red”]MAG[/COLOR] (myelin associated glycoprotein). MAG sits between Schwann and Axon cells in extra-cellular space. It has “feelers” extending into the Schwann cells affecting microtubules. Destroying MAG interferes with normal functioning of the microtubules and the Schwann cells leading to demyelination. So the action is indirect unlike in CIDP which might explain the much slower progression of the disease. Another aspect: in my case the activated B cells (plasma cells) producing the antiMAG IgM don’t die after their normal 4-5 days life span.

I highlighted [COLOR=”Red”]MAG[/COLOR] in red in the diagram below (left side):
[IMG]http://www.ourbluemarble.us/forum/MAG.jpg[/IMG]
Here a definition of microtubules:

[QUOTE]Microtubules are conveyer belts inside the cells. They move vesicles, granules, organelles like mitochondria, and chromosomes via special attachment proteins. They also serve a cytoskeletal role. Structurally, they are linear polymers of tubulin which is a globular protein. These linear polymers are called protofilaments. The figure to the left shows a three dimensional view of a microtubule. The tubulin molecules are the bead like structures. A protofilament is a linear row of tubulin beads.

Microtubules may work alone, or join with other proteins to form more complex structures called cilia, flagella or centrioles.[/QUOTE]

Thanks, Norb – this is some new info for me. I have read that mag is instrumental in the “communication” between the schwann cell and the axon for maintenance of myelin. Excellent Picture!! – it can help when reading these complicated publications.

Something I’ve wondered about – just curious – do you have an excess of IgM (and lower amounts of IgG et al) or just a sensitivity of IgM to mag?

I’ve always thought you could benefit from Rituxan – if you had impaired switching of IgM to IgG, I’ve read that is classified as “immune deficient”. It could be a “back door” argument to get the Ritux approved for you. By the way, a new, fully humanized form of anti-cd20 therapy is now being used with success – you may have heard of it – HuMax.

best wishes,
cd

CD, I have a very high antiMAG IgM titre, 190,000 vs. normal <1500. I don't think IgG is low. The argument "immune deficiency" probably won't work. As far as I know using Rituxan for anything other than nonHodgkins Lymphoma is considered experimental.
Havn't heard of HuMax.

[QUOTE=norb]A good source would be a paperback which I found very useful in understanding the immune system. Lots of diagrams. It has a chapter on autoimmune diseases. “Life, Death and the Immune System” a Scientific American special edition, 136 pages, W.H. Freeman and Co, New York. It is out of print but I’ve seen it used for around $5 at amazon.com. Some of it may be outdated and newer research is missing. But the basics have not changed.[/QUOTE]

Hey Norb…I just ordered that book for 5 cents (plus shipping of course)!!!
Can’t wait to get it.

Andrew

Andrew, you really can’t beat that. Hope you like the book. I refer back to it all the time. Some of the illustrations I’ve posted here in the past are from the book. Except the one about MAG earlier in this thread came from somewhere else. I just fixed the link so it shows up again.

Another good resource is the online immunology course from the faculty of medicine at the Dalhousie University in Halifax.

[url]http://pim.medicine.dal.ca/imman.htm[/url]

I’m still trying to understand where and how things are going wrong with our immune system. I’m planning to go back to this cource and study it in more detail.