Melinda - Anti-MAG antibodies

I just came across this while poking around for Julia. Have you ever been tested for this? Since you have immunoglobulin deficiencies, maybe there is some connection (or I could be way off). Anyway, thought it was worth a shot.

This study will test the safety and effectiveness of the drug Rituximab in treating a nerve disease called MGUS (also known as neuropathy with anti-MAG antibodies). Patients with MGUS have an abnormal protein called monoclonal IgM immunoglobulin that attacks the myelin sheath (protective coating) of nerves, causing them to not function properly. The disease affects the nerves in the legs or arms, and patients have numbness, tingling, muscle weakness, and unsteady gait. There are no adequate treatments. Immunosuppressive drugs or human immunoglobulin infusions can produce mild and transient improvement, but the benefits of these therapies are not significant.

The abnormal immunoglobulin protein in MGUS is produced by white cells called B lymphocytes. Rituximab is approved to treat B cell lymphomas. Also, the drug showed promise in a recent study of patients with demyelinating neuropathy associated with production of antibodies from B lymphocytes directed against certain nerve proteins. Although the number of patients treated with Rituximab was small, the drug was well tolerated and caused significant improvement in several of the patients.

Patients 25 years of age and older with MGUS may be eligible for this 2-year study. Candidates will be screened with a medical history, physical and neurological examinations, and blood tests.

Participants will be randomly assigned to receive intravenous (through a vein) infusions of either Rituximab or placebo (a solution that looks like Rituximab but has no active ingredient) once a week for 4 consecutive weeks. In addition, they will undergo the following tests and procedures:

Monthly follow-up visits following Rituximab treatment for repeat physical and neurological examinations, blood tests, muscle strength measurements, and review of signs and symptoms.
Two sessions of lymphapheresis, one at the beginning of the study and one a year later-to collect lymphocytes. For this procedure, whole blood is drawn through a needle in an arm vein, much like donating a unit of blood. The blood then flows through a catheter (plastic tube) into a cell separating machine, where the white blood cells are extracted and removed. The red cells and plasma are then returned to the body through a needle in the other arm. The procedure takes about 60 to 90 minutes.

Electrophysiologic studies (electromyography and nerve conduction testing) are done once at the beginning of the study and again one year later. For electromyography, a small needle is inserted into a few muscles and the patient is asked to relax or to contract the muscles. The electrical activity of the muscle cells is recorded and analyzed by a computer. For nerve conduction testing, nerves are stimulated through small wire electrodes attached to the skin and the response is recorded and analyzed.

If this study indicates that Rituximab is beneficial against MGUS, patients who were assigned to receive placebo during the trial will be offered treatment with Rituximab (four weekly infusions) at the end of the study.

clinicaltrials.gov/ct2/show/NCT00050245

Just throwing these out there.

Summary of "Rituximab in patients with chronic inflammatory demyelinating polyradiculoneuropathy: a report of 13 cases and review of the literature."

Background A few case reports have shown controversial results of rituximab efficacy in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Objective To analyse the efficacy of rituximab in a large CIDP cohort. Methods A retrospective, observational and multicentre study on the use of rituximab in CIDP. 13 Italian CIDP patients were treated with rituximab after the partial or complete lack of efficacy of conventional therapies. Eight patients had co-occurring haematological diseases. Patients who improved by at least two points in standard clinical scales, or who reduced or discontinued the pre-rituximab therapies, were considered as responders. Results Nine patients (seven with haematological diseases) responded to rituximab: six of them, who were non-responders to conventional therapies, improved clinically, and the other three maintained the improvement that they usually achieved with intravenous immunoglobulin or plasma exchange. Significantly associated with shorter disease duration, rituximab responses started after a median period of 2.0 months (range, 1-6) and lasted for a median period of 1 year (range, 1-5). Conclusions Rituximab seems to be a promising therapeutic choice when it targets both CIDP and co-occurring haematological diseases. Timely post-onset administration of rituximab seems to be associated with better responses.



www.bioportfolio.com/resources/pmarticle/11586/Rituximab-In-Patients-With-Chronic-Inflammatory-Demyelinating-Polyradiculoneuropathy-A-Report-Of-13.html

Sandi between Jan 2004 and Feb 2012 the powers that be said I didn't need a hematologist - so that was that. Then needed gum surgery and the specialist wasn't going to work on me without a normal platelet count - couldn't get in to a hematologist until after the scheduled dental surgery but finally got him to agree to do it if PCP said my count was ok for it. See the hematologist the next month, the man is fantastic! and he said yes I should have been seeing him the past 8 years - he ran more tests than I'd ever had before and it was then that I found out about the hypogammaglobulinemia & that it was low back in 2004 and no one told me. I know he ran tests to see if I could have Rituxan if needed. He was concerned since my ITP symptoms first showed up very shortly after a gamma globulin injection. So I don't know if he tested for anti-MAG antibodies. My IgM comes back ok though it is just above the norm low. However I do have a phone appointment with him next month and will ask him about it.

Wonder though if that isn't a question for my neurologist [who looks like he has yet to enter high school ]. Don't see him till next year but I could email him and ask, he'd have to go through my records since he is new & it would have been my old one who would have tested for it.

Thanks Sandi!

Yeah, that should have been a test from the Neurologist. I wonder if he ever did that for you?

Actually, you, Dan and me should all have it.

OPINION STATEMENT:

Polyneuropathies associated with IgM monoclonal gammopathies comprise a distinct entity. In spite of the apparent pathogenicity of the IgM antibodies and the specific immunoreactivity to myelin antigens, the disease has been difficult to treat. This review describes the clinical phenotype, addresses recent data on immunoreactivity of IgM to various nerve antigens, and discusses the latest progress on treatment.Most of these patients present with paresthesias and sensory ataxia followed by a varying degree of sensorimotor deficits. In more than 75% of the patients, the monoclonal IgM recognizes myelin-associated glycoprotein (MAG) and sulfoglucuronyl glycosphingolipid (SGPG), best detected by ELISA, or other peripheral nerve glycolipids. Recent experiments have demonstrated that animals immunized with SGPG develop sensory ataxia, suggesting a pathogenic role for this antigen. Although cladribine, cyclophosphamide with prednisone, and intravenous immunoglobulin have offered transient benefits to some patients, most have remained treatment-resistant. Open label studies and a recent randomized controlled trial indicate that rituximab is emerging as the best agent available, providing long-term benefits to almost half of these patients. Rituximab appears to work by suppressing the IgM as well as the anti-MAG antibodies and by inducing immunoregulatory T cells. Patients with more sensory deficits and higher anti-MAG antibodies are more likely to respond but may require re-treatment after several months.These encouraging results need confirmation with a larger trial. Data on long-term efficacy and immune markers associated with response to therapy or need for re-treatment are still needed.

www.ncbi.nlm.nih.gov/pubmed/20842571

I still might ask my hematologist about this - when I had first appt with my new neurologist last year, wet behind the ears, I asked him if he had looked at my record. You know what he told me? - just from the last appt. Well that appt was with the dang ditz female neurologist who didn't even watch me walk or check my balance, she was more interested in looking at herself in the mirror on the door to my left side [seriously, her look went from me to that mirror I don't know how many times] and so I fired her after that 1st visit as she was a friggin' waste of time and obviously not interested in me or PN.

You know, it just might be good for me to have this new neurologist look for that test, then he'll see my record.

Isn't that frustrating? Sorry you're having such bad experiences with your doctors lately. A good doctor makes all the difference!

It's unreal that Neurologists wouldn't look at causes for PN, especially since it's so progressive and painful. Mine just chalked it up to Lupus and shrugged. Nothing further. Chances are that is the reason, but they could at least look at other reasons. I realized how fallible they were when no one would pay attention to my RLS. Four doctors shrugged. It took me two years of not sleeping more than 3 or 4 hours a night to find the real reason (low ferritin) and I haven't had a problem since. I take iron periodically and it works.

Let me know how it goes.

Geeze - I had a nice long reply and my cast hit something and it's gone.

So the long & short of that reply:
Only really bad experience with a doctor recently was our PCP who wouldn't do right by us, if a doctor won't stick up for you that is bad. So got rid of him fast.

This ditz of a neurologist - believe me she had no reason to be looking past me and at herself in the door mirror, Body Beautiful she was not. So last year the new wet behind the ears neurologist, I'm sticking with him as I think he will be good - but he needs to go beyond the visit with Dr. Conceited, and I told him that last year. You know I think he did because last year he couldn't tell me which leg had the muscle weakness, this year's visit he could.

So I will bring up the above to him and I might also bring it up to my hematologist too. I do know my original neurologist [my warm fuzzie] did gobs and gobs of tests when he first saw me, I thought I'd have no blood left in my veins when I saw all the tubes to be filled - but I don't recall what all they were. Know my hematologist did test to see if I could have rituxin.

Story about my hematologist and then I'll be quiet. Old forum - man in Utah with an ITP brother somewhere near me - could tell from what Utah Brother said that ITP Brother Here had a good hematologist and also had same medical as me - I messaged Utah Brother and he gave me ITP Brother Here's hematologist's name so when I needed one I could ask for him - that's exactly what I did a couple years ago when needed "permission" to have the dental surgery. I really do like this hematologist.

As for women and doctors - you know sometimes I feel..... An acquaintance died from a brain aneurysm, she'd gone to the doctor for months complaining about headaches and not feeling right and he'd just tell her it's all in your head, he was right it was and it killed her leaving behind her husband and young son to mourn her loss - was her death necessary? It has haunted me for many years now.

I am so glad you are finally sleeping again - need to ask my aunt who has RLS if her ferritin has been tested.


PS - have you directed Dan to this thread?

Melinda wrote: PS - have you directed Dan to this thread?

Not yet, but I will.

Maybe your original Neuro did test for it, but things change and antibodies come and go. Wouldn't hurt to ask.

Darn cast! I lost a bunch of stuff that I wrote yesterday and I don't even have a cast (Just an empty head)! When do you get it off?

I've got the EHS [Empty Head Syndrome] too
Will have the cast at least another 4 weeks - then a brace & OT

I've lost so much typing like that, that now if it is a long post I type it into Microsoft Word then cut & paste it here.

Sandi wrote:

Melinda wrote: PS - have you directed Dan to this thread?

Not yet, but I will.

Maybe your original Neuro did test for it, but things change and antibodies come and go. Wouldn't hurt to ask.

Darn cast! I lost a bunch of stuff that I wrote yesterday and I don't even have a cast (Just an empty head)! When do you get it off?

Can I get tested for this even though I went through 4 rounds of Rituxan in Dec 2012? I know they at UCSF wanted to test for all kinds of things,(never said what) but they said I'd have to wait at least 18 months to 2 years after to get these kinds of tests. They said that it stays in the body a long time. which is why it's so useful in treating ITP.

Hmmm....I've always read that Rituxan is gone after six months to a year. At any rate, I'd think you are close enough to their 18 - 24 month waiting period.

My new Neurologist wants to run this after she has gathered all my records from my other doctors. She said that for some reason UCSF is dragging their feet on sending her info.

Good! I'm glad she is checking into it. I'll have to write it down to remember to mention it at my next appointment (October).

I've always had that problem too - records taking forever to get forwarded. I used to always get copies of labs and then I'd have them myself for new doctors, but it got to be too many doctors to keep track of.

I now have 8 different doctors to try and keep up with. So I make sure that my PCP has everything vs. me trying, I do keep all the reason for visit forms.

My docs send everything to my PCP, but I never see him. He's too clueless to be any help. He prescribes my blood pressure med, that's it. If I'm sick I see the PA and we deal with the illness only. I have so many smaller issues that should be addressed, but never seem to get to it.

Glad she is going to check it out Dan. She sounds good!

[that's why I like my HMO - everything is there for all doctors and pharmacists to see - and the hospital]

I guess I must be lucky. My PCP rarely sends me to her PA and she actually coordinates what the other doctors are doing and she discusses everything with me either by phone or in person. And if there is something that she's unsure of she researches or calls others to make sure that what is being done is in my best interest.