Hi Rocky 36
Interesting information that you posted.
As one of a few Forum members who have MGUS, I’d like to make a few comments on what is stated by both the Oncology/Hematology site and the Mayo Clinic.
Actually, about one percent of the population over 50 (and about 3% over 70) has MGUS. The monoclonal gammopathy can be associated with different proteins – IgM, IgG, IgA.
In a small percentage of these patients, the protein produced is an anti-MAG and the result is peripheral neuropathy. This occurs mostly with the IgM, but is also found to occur from time to time with the other two proteins.
In my opinion, by “association with CIDP”, they are suggesting that the very same description “chronic inflammatory demyelinating polyneuropathy” applies to MGUS as it does to CIDP. However, I have never before heard that someone with MGUS will develop CIDP (as a distinctly separate disease from MGUS). By association, I would think that they are suggesting that MGUS can lead to neuropathy.

I am a bit puzzled too by the Mayo clinic statement that it is the plasma cells that produce the antibody. Some of us take Rituxan which targets the B cells with CD20 markers, but the plasma cells, in my understanding do not have the CD20 marker. However, Rituxan has been proven to work. Therefore, some of the protein must be produced in cells other than the plasma cells. I am not a doctor or a biologist so my knowledge is rather limited and I have only learned all this stuff in the last couple of years since my IgM MGUS diagnosis and the problems of PDN. Because B-cells become plasma cells eventually, perhaps the trick is to eliminate those B-cells destined to becoming the “bad plasma cells” before they get there. I wish I knew more about all this.

There is proven to be a conversion rate from MGUS to various forms of cancer as you had listed of about 1% per year. This conversion rate was shown to be non-cumulative (1% year 1, 2% year 2, etc). Your chances are always one percent each year so the chance in year 20 if it hasn’t happened already is still 1%. But over a 25 year period, the chance of conversion to a form of cancer would be 25%.

Anyway, most people with MGUS don’t even know that they have it. Generally it shows up in a routine blood test which might include the protein electrophoresis.

I hope that my posting hasn’t merely confused the issue further.
Andrew

Great info…thanks Rocky.

Reminded me of something: my mom had rheumatoid arthritis (RA) which only became active after she had colon cancer. I’ve done my own little non-scientific study of people I know who have, or have relatives that have, RA. An amazing majority say that a cancer came first, then the RA.

My thought has always been that cancer is the ultimate auto-immune disorder, and that somehow it throws your entire autoimmune system off-track.

As CIDP is an autoimmune disorder, this all makes perfect sense. Guess I’ve assumed for quite some time that once you have one AI disorder that you’re more susceptible to others. This may explain why that is.

Thanks again!

I agree with Elmo, about cancer is an autoimmune disease.
I think this is the reason why there is not a cure ofr it yet,
until docs start managing it as an autoimmune disease.
We have billions of cells, and there is no way cells no to be mutants,
I think we all have the sme mutants cells, the differential to cancer pacients,
is that de inmmune system does not recognice this cells as antigens and attack them.
In our case in reveresal, our healthy nerve cell are seen as antigens and attacked.
Pablo,

Yes there are at least 3 of us here. I have MGUS and CIDP among other things although other then “having” it, nothing much has come of it or been done so far. I never know which illness causes which issues either but more then likely your aches and pains are GBS residuals.

Jerimy

It hasn’t been that long for me since I was diagnosed with it. I am on a 6 month return visit setup with all of my Doctors so I assume they will test again then. If I run across any information or anything I will pass it along to you, my email is [B][SIZE=1]jerimyschilz at hotmail dot com[/SIZE][/B]

Contact me anytime if you need to. Take care.

Jerimy

[QUOTE=Iowagal]Does anyone else here have MGUS? I was found to have MGUS (Monoclonal gammopathy of undetermined significance) while in the hospital for GBS. It can also cause neuropathies so sometimes I am unsure if my weird aches and pains are GSB residuals or a result of MGUS.[/QUOTE]

Hi, yes I do have MGUS, was diagnosed in February and every 3 months I have to go for blood checkups. I also experience polyneuropathy in my feet and hands, and even my yaws seem to start feeling strange.
Does anyone experience the same here? I live in Holland, Europe hence my nickname Dutch girl.

Wishing all of you / us the very best and hoping to hear from you also on how you cope with muscle fallout/pain.

[QUOTE=Jerimy]It hasn’t been that long for me since I was diagnosed with it. I am on a 6 month return visit setup with all of my Doctors so I assume they will test again then. If I run across any information or anything I will pass it along to you, my email is [B][SIZE=1]jerimyschilz at hotmail dot com[/SIZE][/B]

Contact me anytime if you need to. Take care.

Jerimy[/QUOTE]

Hello Jerimy

I was diagnosed MGUS in February and ever since I go for bloodcheck ups every 3 months. Neuropathy in both feet and hands and feeling in my yaws seem to change. Oh well, I guess we all cope as it is. I do admire your cheerfulnes and I try to look on the bright side. Am working 28 hrs weekly and up to now can manage quite well. But all of a sudden I feel progression and that does worry me. I do not yet receive any medication. How did and do you experience your MGUS? Any suggestions as to trying to slow down the process?
My hometown is Pijnacker, The Netherlands hence my nickname Dutch girl.

Take care and hoping to hear from you. All the best, regards

Hi Iowagal

Thanks for our reply. I have no idea what type of MGUS I do have and quite frankly I find the cooperation with neurologist and oncologist quite frustrating. I check up every 3 months, next September again, and thats for the blood part. I am sure to ask them more info and want the results this time so I know more details. Unless one asks one never gets all the facts. I was wondering whether MGUS can be halted at all, as it seems to gain terrain so to speak. Have just turned 57 and if the progressing rate is going to continue I will not be albe do to much of anything properly in a short time. How do you expenrience this and do you know if MGUS can be slowed down with any drug?
I live in The Netherlands, whereabout did your ancestors come from?
Take care and keep smiling (I always do :D)
kind regards,
Dutch girl:)

Dutch girl it is so nice to meet you. I try and remain positive, it’s hard to help people if I don’t. My MGUS remains a mystery to me although I have plenty of other diseases that occupy my time. Here is some information I had saved on MGUS, hope it helps:

From [I][B][url]www.myeloma.org/main.jsp?type=article&id=879[/url][/B][/I]

“What is monoclonal gammopathy of undetermined significance (MGUS)?
ByMorie Gertz, MD
2.28.03 The finding of a monoclonal protein or MGUS means that there is an abnormal protein that has been detected in your blood tests. Typically this protein is found during a routine physical examination and is identified using a screening blood test called “protein electrophoresis.” This protein by definition is not associated with more serious problems that are typically associated with protein abnormalities such as multiple myeloma. The source of this protein is a small population of plasma cells in the bone marrow. Plasma cells are present in the bone marrow of all normal adults and represent approximately 1% of all of the bone marrow cells. Plasma cells’ normal function is to produce antibody proteins that help protect your body against infection.
On mass screening, the finding of an abnormal protein in the blood is not rare. In fact, 2% of adults over the age of 50 will have this as an incidental finding during screening examinations. However, the frequency with which these proteins are found rises as we age. At age 70 the incidence is from 3 to 4%. The finding of this abnormal protein will occur in both sexes and in all races and is not limited based on occupation or background.
The finding of an abnormal protein in the blood (MGUS) will not produce any symptoms. Detecting an abnormal protein is generally not a concern and extensive testing is generally not required unless there are symptoms that warrant a greater index of suspicion on the part of your physician. Follow-up is required for all patients indefinitely, and your physician will monitor protein levels regularly.
The protein noted above is found on a serum protein electrophoresis test; when this test is performed, the blood protein is separated into five component proteins. The monoclonal protein graphically will look like a peak or spike. Physicians often refer to this as a blood spike and, again, this finding may not require any additional testing if there are no other pertinent physical findings or symptoms.
Treatment for monoclonal gammopathy is not required, although research protocols are in existence for patients at centers that specialize in the treatment of monoclonal gammopathy and multiple myeloma. The reason why these proteins are a concern is that patients who have them have a higher risk of developing a more serious blood or bone marrow problem such as multiple myeloma. Fully 80% of patients with a protein abnormality will never develop any problems related to it. However, because 20% of patients might go on to develop problems, careful follow-up is required. This may only require an annual blood test. This blood test, protein electrophoresis, can be done in virtually any hospital laboratory. For most individuals, a bone marrow examination is not required. More in-depth testing may be done if the protein level has changed or if symptoms develop.
It must be kept in mind that a monoclonal gammopathy does not represent cancer. However, because patients with monoclonal proteins are at risk of developing multiple myeloma or related disorders, lifelong monitoring is required. The presence of the protein, since it is derived from bone marrow plasma cells, is not impacted by your diet or the amount of protein you consume, since dietary protein and the production of monoclonal proteins are unrelated. There is no increased risk of monoclonal gammopathies in first-degree family members; therefore, your siblings and children do not need to be screened for the presence of an abnormal protein.
In summary, the finding of a monoclonal gammopathy is not an indication for treatment, generally does not require invasive testing, and is not a cause for overt concern. One must be prudent, however, since there is a risk, albeit small, that patients with monoclonal proteins could develop more serious disorders. Close monitoring will allow your physician to intervene before problems occur. Therefore, annual testing is appropriate.”

[QUOTE=Jerimy]Dutch girl it is so nice to meet you. I try and remain positive, it’s hard to help people if I don’t. My MGUS remains a mystery to me although I have plenty of other diseases that occupy my time. Here is some information I had saved on MGUS, hope it helps:

From [I][B][url]www.myeloma.org/main.jsp?type=article&id=879[/url][/B][/I]

“What is monoclonal gammopathy of undetermined significance (MGUS)?
ByMorie Gertz, MD
2.28.03 The finding of a monoclonal protein or MGUS means that there is an abnormal protein that has been detected in your blood tests. Typically this protein is found during a routine physical examination and is identified using a screening blood test called “protein electrophoresis.” This protein by definition is not associated with more serious problems that are typically associated with protein abnormalities such as multiple myeloma. The source of this protein is a small population of plasma cells in the bone marrow. Plasma cells are present in the bone marrow of all normal adults and represent approximately 1% of all of the bone marrow cells. Plasma cells’ normal function is to produce antibody proteins that help protect your body against infection.
On mass screening, the finding of an abnormal protein in the blood is not rare. In fact, 2% of adults over the age of 50 will have this as an incidental finding during screening examinations. However, the frequency with which these proteins are found rises as we age. At age 70 the incidence is from 3 to 4%. The finding of this abnormal protein will occur in both sexes and in all races and is not limited based on occupation or background.
The finding of an abnormal protein in the blood (MGUS) will not produce any symptoms. Detecting an abnormal protein is generally not a concern and extensive testing is generally not required unless there are symptoms that warrant a greater index of suspicion on the part of your physician. Follow-up is required for all patients indefinitely, and your physician will monitor protein levels regularly.
The protein noted above is found on a serum protein electrophoresis test; when this test is performed, the blood protein is separated into five component proteins. The monoclonal protein graphically will look like a peak or spike. Physicians often refer to this as a blood spike and, again, this finding may not require any additional testing if there are no other pertinent physical findings or symptoms.
Treatment for monoclonal gammopathy is not required, although research protocols are in existence for patients at centers that specialize in the treatment of monoclonal gammopathy and multiple myeloma. The reason why these proteins are a concern is that patients who have them have a higher risk of developing a more serious blood or bone marrow problem such as multiple myeloma. Fully 80% of patients with a protein abnormality will never develop any problems related to it. However, because 20% of patients might go on to develop problems, careful follow-up is required. This may only require an annual blood test. This blood test, protein electrophoresis, can be done in virtually any hospital laboratory. For most individuals, a bone marrow examination is not required. More in-depth testing may be done if the protein level has changed or if symptoms develop.
It must be kept in mind that a monoclonal gammopathy does not represent cancer. However, because patients with monoclonal proteins are at risk of developing multiple myeloma or related disorders, lifelong monitoring is required. The presence of the protein, since it is derived from bone marrow plasma cells, is not impacted by your diet or the amount of protein you consume, since dietary protein and the production of monoclonal proteins are unrelated. There is no increased risk of monoclonal gammopathies in first-degree family members; therefore, your siblings and children do not need to be screened for the presence of an abnormal protein.
In summary, the finding of a monoclonal gammopathy is not an indication for treatment, generally does not require invasive testing, and is not a cause for overt concern. One must be prudent, however, since there is a risk, albeit small, that patients with monoclonal proteins could develop more serious disorders. Close monitoring will allow your physician to intervene before problems occur. Therefore, annual testing is appropriate.”[/QUOTE]

Jerimy
Thank you so much for your detailed information! I have found quite a few sites on the subject, but I do realize that information from those experiencing the same are so valuable. I am not too well informed at present by my specialist but will ask further details this September and can then compare facts with the information I find in this forum. Very helpful indeed.
Take good care, kind regards to you and all
Dutch girl

Your very welcome, get ahold of me anytime if I can be of any help.

Take care,
Jerimy

Hi to the folks in this thread. I am relatively new to the forum so I am still finding my way around and just tonight noticed the MGUS thread and the post from Dutch Girl asking if anyone else has MGUS.
I was diagnosed with IgM MGUS in September after 9 months of tests. I don’t think I have anything else besides the MGUS. At least they did not find anything else. I’ve had the peripheral neuropathy thing, first in the toes, then through the feet, then in the hands, then in the lower legs. At the same time there has been a gradual weakness that I notice when I try to walk fast, etc.
Treatment recommended is Rituxan – series of 4 infusions, one per week.
I’ll let you know how it goes. I have another infusion tomorrow.
Andrew

Hello across the North Sea from northern England to Dutchgirl in Pijnacker, Netherlands.

You should really find out which antibody, IgM, IgG or IgA your MGUS associated neuropathy or PDN is. For more information may I respectfully suggest that you have a look at my website named on my signature below.

I coped with mine for years but in recent years that coping with increasing pain has overtaken me. Just be aware of the need to ask your neuro and or oncologist appropiate questions. Where are they based?:o

I have had MGUS since 2002 when I also was dx with Sjogren’s Syndrome. i got my blood checked several times a year. My IgM spike went up to 1500.
I now have SGPG and Anti-Mag elevations. I will ask MD on my next visit if some of my symptoms are from these, which can cause a slow, insidious, relentness, neuropathy, or if all is from the dx CIDP in Nov 2007.
Sept 2007 is when my first symptoms appeared and by Nov 2007 could no longer without a walker or being i n a w/c. all other physical sympotoms remain.
I’m going to start a new dance craze when I can stand again called the electric shock dance.
Keep us posted

Hi, I just discovered this thread today. I am one of the few unfortunate individuals who has MGUS with not so “uncertain significance”. I was diagnosed with it fall of 2005 along with CIDP and a high titre of anti-MAG IgM (140,000). Symptoms started in 2001 with slight numbness in my toes and have been progressing steadily ever since. Today feet are totally and hands are mostly numb. There is also partial numbness and weakness in my legs and last year my tongue started to get numb also. Because of all this and pronounced ataxia I started using a power chair about six weeks ago. IVIG’s have been of limited benefit and prednisone was a complete disaster.

Last August — on my insistence — I was diagnosed with asymptomatic indolent lymphoma as the most likely underlying cause for all my symptoms. This finally qualified me for Rituxan. I received four infusions over a period of four weeks in October. I am still waiting for significant improvements, however, my tongue is almost back to normal and some sensation has returned to my fingertips. Unfortunately, there still seems to be a significant amount of anti-MAG IgM in circulation. I’m scheduled for another round of Rituxan next month.

The literature states — that aside from standard chemotherapy — Rituxan is one of the few treatments which may be effective for anti-MAG IgM neuropathy.

By the way, this neuropathy is considered by some (including my neurologist) to be a variant of CIDP while others treat it as a separate disease: PDN (paraproteinemic demyelinating neuropathy).

Iowagal,
I don’t know much about GBS residuals but I’m sure you have seen posts about CIDP diagnosis following GBS. Have you discussed this with your neurologist? As you know, your monoclonal IgG could be harmless or be directed toward the myelin and/or nerves. It is possible for the IgG to also be directed toward MAG. I’m sure there are tests to determine that — possibly the same one used for IgM.

If you want to do any research, this excerpt from a book by Latov “Neuropathy” might be a good start.

[IMG]http://www.ourbluemarble.us/forum/IgG_MGUS.jpg[/IMG]

Prior to IVIG infusion on March 10 & 11 lab work was drawn. My IgG was 317, IgA 3 and IgM 743.
I’m confused as i have been getting IVIG for five months, with no improvement, just holding a steady course. I thought that IVIG was to increase anti-bodies?
Also does CellCept lower the immunoglobulina’s.
Guess, i don’t really understand the suuppression of the immune system and I’m on three different suppressants. CellCept 2000mg, Prednisone 60 mg, and Arava 20 mg a day.
Does anyone have info on this subject or a web site to go to
Thanks a head of time.:confused:

Beth, most sources I found don’t explain in detail how immune suppression works except that it reduces the activity of the immune system. Production of antibodies obviously is one of the activities. The medications you’re taking apparently are working well for IgG and IgA since your results are way below normal. However IgM is way above normal which seems very odd to me. I’m also surprised about how many immune suppressing drugs you are taking. But I’m not very familiar with what commonly is being done.

IVIG should be adding antibodies to serum but their half-life generally is relatively short, IgM for example is only four to five days.

I’m sorry I don’t have more information for you.

Here is more: I don’t know why I didn’t think about this before but I pulled out my textbook, [I]Immunology[/I] by Klaus Elgert. There are several pages on the topic of immunosuppression which I never studied before, probably more than either one of us care to know. I will try to summarize the important sections.

There are three methods:

[B]1. Physical methods[/B], i.e. removing the immune systems cells and tissues, surgery etc.
[B]2. Chemical methods[/B] (more about this below)
[B]3. Biological methods[/B] such as using antigen or antibodies. The exact mechanism of action for biological immunosuppressive agents are not thoroughly known. IVIG and Rituxan belong here (my comment)

[B]Chemical immunosuppressants[/B] can be placed in four main groups: corticosteroids, alkylating agents, anti-metabolites, and antibiotics.

I don’t know where the CellCept and Arava you are taking belong.

[B]Steroids:[/B] in humans the immunosuppressive effects of steroids are poorly defined. [I]Cortisone[/I] for example mediates lysis of susceptible lymphocytes and anti-inflammatory actions. They cause the cell nucleus to disintegrate and cells to lose their cytoplasm. Unlike other immunosuppressants, they are effective whether or not cells are in their replicative cycle.

[B]Alkylating agents[/B]: these interfere with some basic metabolic processes needed for cell division, differentiation or protein synthesis. The main effect is on DNA synthesis by adding alkyl chemical groups to nucleic acids and proteins. They destroy lymphocytes and reduce proliferation. Well-known drugs are [I]Cyclophosphamide [/I](Cytoxin) and [I]Chlorambucil[/I].

[B]Anti-metabolic agents:[/B] they also interfere with basic metabolic processes[B],[/B] primarily inhibiting cell division. They function as antagonist of folic acid as well as purines or pyrimidines. All these are essential for DNA synthesis. They resemble natural molecules but lead to faulty cell metabolism. Of interest for us, of course, would be the inhibiting effect on T and B-cell proliferation.[I] Imuran[/I] would be one of these drugs.

[B]Antibiotic agents[/B]: some of them have immunosuppressive activity. One example is [I]Cyclosporin A[/I]. It differs from other immunosuppressive drugs because it is not lymphocytic and has selectivity. Its principal target is the Th(helper T) cell. It suppresses T-cell growth and differentiation without directly affecting antibody production or impair marrow function.

I hope this helps.
Take care

Just to add to the stock of knowledge of MGUS associated neuropathy that is now known in Europe as Paraproteinaemic Demyelinating Neuropathy – PDN.

In 2006 the European Federation of Neurological Societies and the Peripheral Nerve Society published a report of a joint task force on the management of the PDNs.

You can read the whole of it on a pdf at [url]http://pns.ucsd.edu/Guidelines_paraproteinemic_neuropathy.pdf[/url]

Plenty to read there.:)

Thanks for the info and web sites. They are very helpful.

Iowagal on 18th March.[QUOTE]It was interesting reading since doctors do not generally seem to associate neuropathy with IGG MGUS.[/QUOTE]
Which doctors are these?

IgG, IgA, IgM (not the anti-MAG type) and anti-MAG IgM can all be associated with neuropathy.

I have a question for anyone who might be able to help. In a normal person, that is someone without any spikes in their immunopherisis, are there naturally occuring anti-MAG titers, or does the anti-MAG only show up in those with IgM PDN (DADS)?
The reason I ask is because in all studies I’ve seen, there are no instances of patients who got down to zero anti-MAG levels with Rituxan treatment. So I wondered whether the immune system makes these proteins at some low level as a normal course of events.
Andrew

Andrew,
I could not find the reference in which the author suggests that anti-MAG IgM may be present from birth. But there is a related excerpt from a book by Latov Chapter on antiMAG Pathology:
[QUOTE]Anti-MAG M protein secretion in vitro is subjected to T cell regulation (Latov et al 1985) and anti-idiotypic antibodies to the M protein has been demonstrated in some patients (Nobile-Orazio 1985) suggesting that anti-MAG M protein secretion, though abnormally increased, is somehow regulated as also indicated by the fact that in most patients anti-MAG M protein levels are stable for years and rapidly return to their original level when treatment directed at their reduction is suspended. Whether these antibodies may also have some as yet unknown regulatory role on the immune system (Tanaka et al 1985) is not known but may prompt some caution on the risks of therapies directed at reducing M protein levels in these patients.[/QUOTE]

Thanks Norb
I guess that might help to explain why we never see any studies where the patients given Rituxan (single doses, doubles doses, whatever) reach a point of having no anti-MAG in their system. There always seem to be residuals.

I wonder what purpose the anti-MAG has within the immune system. Even though the damn stuff is eating away at our nerves, Olde Mother Nature usually did things for a purpose. The whole subject of regulatory roles as in the quote seems very complex. This all ties in with the business of the T cells, which may be good for us in their regulation of B cells, BUT, as long lived memory T cells, could perhaps be responsible for maintaining a certain level (normal level?) of anti-MAG.

Having flunked organic chemistry several times and that being the closest thing to biology that I ever studied (other than adding yeast to the wort in order to make beer), I find myself in a totally new arena. I sure wish I knew more biology. :confused:

The one great biology teacher and medical teacher has been this Forum.
I’ll take this opportunity to once again say that this Forum and the people on it is the best thing that could have happened to me since my toes started to go numb!
Andrew