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Holy crap -- IgM deficiency

SOC

Senior Member
Messages
7,849
What are you taking right now? Is there any possibility that you're taking immune modulators that could be throwing off the lymphocyte subset panel?

Have you and your daughter done 23andme at all, or any other type of genetic study?

SPEP is a good test to do and imo indicated when there are strange results on lymphocyte panels coupled with Ig deficiencies. Hopefully (and probably) it will be normal which is one less thing to worry about.

Chest x-ray is also useful if you are concerned about Hodgkin's Lymphoma - but that is based on your family history rather than any specific abnormalities in the testing you just listed for me.

When is your appt with the hematologist?

Have you had bad reactions to any vaccines in the past?
I don't know what immune modulators would be likely to throw off a lymphocyte subset panel. I take Valcyte, which reportedly has immune modulating effects. I know some of the supplements I take are reported to have an effect on NK cells (number or function, I'm not sure).

Daughter and I both did 23andme and didn't see any results that would suggest a well-known genetic immune disorder.

I'm not particularly worried about Hodgkin's Lymphoma. It's more a matter of being a little more alert to immune abnormalities. With at least three cases of Hodgkin's Lymphoma, at least three cases of ME/CFS, and one very severe case of poliomyelitis in the past three generations, there's reason to suspect a genetic weakness in our ability to control viruses. No big worries, just reason to pay attention.

My appointment with the hematologist is Monday. I see Dr Klimas at INIM 10 days later. I should have a lot more data in 2-4 weeks.

I don't typically have bad reactions to vaccines. I get the killed, preservative-free flu shot every year with no problems. IIRC, the last time I had the PneumoVax (about 5 years ago), I felt more than usually crummy for longer than is usual for a vaccine, but it was nothing serious.

My daughter's ME got much, much worse after a bunch of pre-college boosters all on the same day, including a live VZV booster. That's the only time either of us had a problem with vaccines.
 

Eeyore

Senior Member
Messages
595
Valcyte could definitely be the root of this. It is known for causing reductions in white counts - in fact I would say that is likely the cause, unless the same abnormalities preceded the valcyte.
 

SOC

Senior Member
Messages
7,849
I think there are quite a few people, myself included, that have decreased IgG levels.

Although I've never been able to figure out how I could have low total IgG levels and yet antibodies to all these infections are off the charts. Are they a different sort of IgG?

@SOC, if you followed up with an immunologist, they would probably want to do a vaccine challenge to see if you could mount an antibody response. Without a history of recurrent bacterial, usually respiratory type infections, most immunos don't seem all that concerned. Why recurrent chronic viral infections aren't considered is yet another mystery to me. Probably because conventional medicine doesn't recognize chronic EBV etc for the most part anyway.
My INIM doc is an immunologist, so hopefully I'm covered there. We've just started talking about a vaccine challenge. I believe she was waiting until my IgG was consistently below range because she felt insurance wouldn't cover IVIG or SCIG until my IgG was low AND I failed the vaccine challenge.

My problem with a history of recurrent URI's is that my stupid local money-making venture calling itself a medical clinic kept claiming my symptoms were allergies (based on no testing) or asthma (also untrue as demonstrated by testing ordered by my specialist years later). Anything to keep from acknowledging I was ill or giving me any medications. Since I eventually recover (after months and months of URI symptoms), they feel justified in not treating. So my medical record doesn't show many recurrent infections, only the ones that eventually led to pneumonia. I finally gave up going to my PCP with infections because they only implied I was a whiner, gave me no treatment, and charged me an arm and a leg for the privilege. :mad:
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
I swear people get better in spite of the medical system and not because of it. Grrrr.

I hope they do more testing, @SOC. Sounds like you do have the right kind of history and your numbers are getting there too. It's worth a shot.
 

SOC

Senior Member
Messages
7,849
Read the part under warnings and precautions:

http://www.valcyte.com/hcp
I don't get what you mean. My granulocytes are perfectly normal. My RBC and WBC are normal. We are always on the watch for neutropenia and it has never been a problem. I don't know enough about immunology to know which part of the warnings you think apply to my lymphocytes being low. Can you clarify?
 

Eeyore

Senior Member
Messages
595
"Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been observed in patients treated with Valcyte or ganciclovir
Do not administer if the absolute neutrophil count is <500 cells/μL, the platelet count is <25,000/μL, or the hemoglobin is <8 g/dL
Use with caution in patients with pre-existing cytopenias, or who have received or who are receiving myelosuppressive drugs or irradiation. Cytopenia may occur at any time during treatment and may worsen with continued dosing. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug"

I can't claim sufficient knowledge of the mechanism of valcyte's hematologic side effects, but you do have cytopenias. I can't say for certain if it's the valcyte, but do you know if the problem goes back before you started on valcyte? You don't seem to have a broad leukocytopenia based on your report that your CBC is normal, but you do have cytopenias of some classes of lymphocytes.

I think the hematologist might know better - but any data you have that shows changes over time would be very useful (i.e. before and after the valcyte). Valcyte is not a completely benign/safe drug. It's not selective in the way valtrex is - although it's broader spectrum. Many more side effects with it though.

It could be causing some kind of bone marrow suppression that is not obvious on a CBC but is showing on a lymphocyte subset panel. I don't know how selective ganciclovir is its bone marrow suppressive properties.

Here's one article on pubmed that shows a suppression of lymphocyte proliferation from valcyte: http://www.ncbi.nlm.nih.gov/pubmed/22155904

A lot has to be considered, but I think this needs to be in the differential. The best way to rule it out (or in) would be to compare results before and after valcyte therapy. How long have you been on it, and what benefits have you noted? What dose? Any particular side effects?
 

Eeyore

Senior Member
Messages
595
I wonder if you might be getting some beneficial effects from valcyte not from the antiviral properties but from the suppression of the immune system... Again, speculation, but it's plausible.
 

SOC

Senior Member
Messages
7,849
"Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been observed in patients treated with Valcyte or ganciclovir
Do not administer if the absolute neutrophil count is <500 cells/μL, the platelet count is <25,000/μL, or the hemoglobin is <8 g/dL
Use with caution in patients with pre-existing cytopenias, or who have received or who are receiving myelosuppressive drugs or irradiation. Cytopenia may occur at any time during treatment and may worsen with continued dosing. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug"

I can't claim sufficient knowledge of the mechanism of valcyte's hematologic side effects, but you do have cytopenias. I can't say for certain if it's the valcyte, but do you know if the problem goes back before you started on valcyte? You don't seem to have a broad leukocytopenia based on your report that your CBC is normal, but you do have cytopenias of some classes of lymphocytes.

I think the hematologist might know better - but any data you have that shows changes over time would be very useful (i.e. before and after the valcyte). Valcyte is not a completely benign/safe drug. It's not selective in the way valtrex is - although it's broader spectrum. Many more side effects with it though.

It could be causing some kind of bone marrow suppression that is not obvious on a CBC but is showing on a lymphocyte subset panel. I don't know how selective ganciclovir is its bone marrow suppressive properties.

Here's one article on pubmed that shows a suppression of lymphocyte proliferation from valcyte: http://www.ncbi.nlm.nih.gov/pubmed/22155904

A lot has to be considered, but I think this needs to be in the differential. The best way to rule it out (or in) would be to compare results before and after valcyte therapy. How long have you been on it, and what benefits have you noted? What dose? Any particular side effects?
Thanks, that clarifies. :) When I looked up cytopenia all I saw was reference to cells that I have in normal numbers. If I understand you correctly, it can mean the reduction in any blood cells, which would certainly apply here.

I am well aware that Valcyte is not benign. For me, it's the difference between being bedbound, and taking care of my ADLs and working full-time, so it's worth the risk... for me.

I don't have pre-Valcyte immune tests, unfortunately. The best info I have is that even when I was off Valcyte for two years, my lymphocytes continued to decline at the same rate. There was no difference between the times I was on Valcyte and when I was off. That doesn't mean Valcyte isn't affecting my bone marrow, just that we don't have any pattern to judge by.

I was on Valcyte for 2 years, then off for 2 years, and have been back on again for a year. I always feel better on Valcyte. I have had no side effects, other than an IRIS-like reaction at the beginning of the first round, after which I felt better is every way -- huge reduction in flu-like symptoms, more energy, much less cognitive dysfunction. After about 2 years off, my HHV6 titres climbed significantly and I got increased exhaustion and serious cognitive dysfunction. My daughter had exactly the same pattern.
I wonder if you might be getting some beneficial effects from valcyte not from the antiviral properties but from the suppression of the immune system... Again, speculation, but it's plausible.
That does not appear to be the way Drs Klimas and Rey see it and they're both trained in immunology. That doesn't mean it isn't possible, or that Klimas/Rey won't change their minds as more data becomes available. At the moment, they think Valcyte is an important treatment for me and they're well aware of my immune status -- they run the tests at their (well NOVA's) lab.

Not all of us are autoimmune subset. Some of us look more immune deficient. I'm in that subset.
 

Kati

Patient in training
Messages
5,497
"Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow aplasia, and aplastic anemia have been observed in patients treated with Valcyte or ganciclovir
Do not administer if the absolute neutrophil count is <500 cells/μL, the platelet count is <25,000/μL, or the hemoglobin is <8 g/dL
Use with caution in patients with pre-existing cytopenias, or who have received or who are receiving myelosuppressive drugs or irradiation. Cytopenia may occur at any time during treatment and may worsen with continued dosing. Cell counts usually begin to recover within 3 to 7 days after discontinuing drug"

I can't claim sufficient knowledge of the mechanism of valcyte's hematologic side effects, but you do have cytopenias. I can't say for certain if it's the valcyte, but do you know if the problem goes back before you started on valcyte? You don't seem to have a broad leukocytopenia based on your report that your CBC is normal, but you do have cytopenias of some classes of lymphocytes.

I think the hematologist might know better - but any data you have that shows changes over time would be very useful (i.e. before and after the valcyte). Valcyte is not a completely benign/safe drug. It's not selective in the way valtrex is - although it's broader spectrum. Many more side effects with it though.

It could be causing some kind of bone marrow suppression that is not obvious on a CBC but is showing on a lymphocyte subset panel. I don't know how selective ganciclovir is its bone marrow suppressive properties.

Here's one article on pubmed that shows a suppression of lymphocyte proliferation from valcyte: http://www.ncbi.nlm.nih.gov/pubmed/22155904

A lot has to be considered, but I think this needs to be in the differential. The best way to rule it out (or in) would be to compare results before and after valcyte therapy. How long have you been on it, and what benefits have you noted? What dose? Any particular side effects?
Valcyte definitely has side effect of cytopenias, on top of possible liver and/or kidney problems. Routine surveillance is on a monthly basis, but weekly during the 3 weeks loading dose.

Personally I have been told by my physician that it decreased monocytes. i haven't had any problems with it.
 

Eeyore

Senior Member
Messages
595
Dr. Klimas is very knowledgeable in immunology and ME in general. I am not saying your symptomatic relief is because of immune suppression, only that it might be. In either case, it makes you feel better...

Hopefully the hematologist can sort out the cytopenias (and yes, it just means a depletion of any class of blood cell - lymphocytopenia is an example). Valcyte can be toxic to bone marrow.

I would expect that if you came off it for a year, lymphocyte levels would at least move towards normal over that time, not decline further.

@Kati - Interesting that it decreases monocytes in particular. That could be useful immunologically.
 

SOC

Senior Member
Messages
7,849
@Eeyore, thanks for a very informative and helpful discussion. :) There's so much I don't know about immunology, and so much we still simply don't know about my immune situation, it's a great benefit to me to be able to speculate about possibilities with people who know more than I do. Obviously, we're not going to figure out anything definite, but I now have a lot more to think about and more knowledge to think with. :D
 

Kati

Patient in training
Messages
5,497
Now that you make me think about it Iccan't remember if it's Rituximab or valcyte that decreases the monocytes. Brain is very, very mush.
 

Daffodil

Senior Member
Messages
5,875
if you have more than one person in the family with CFS, perhaps you might want to get tested for Lyme
 

Eeyore

Senior Member
Messages
595
@Kati - Rituximab primarily targets CD20 on B-cells. I'm pretty sure that monocytes do not express CD20 - I've never heard it mentioned to the best of my knowledge. Rituximab is generally viewed as selective for B-cell depletion. It's used in B-cell cancers as well (not myeloma though, as it doesn't work).

So if it's one of the 2, it's probably valcyte.

I'm inclined to think much of the benefit of valcyte is in the immunosuppressive effects, which are generally viewed as negative side effects - but who knows, it could actually be useful as an antiviral - or even through both mechanisms. Maybe if I looked at some of the Montoya studies through that lens I could figure out if that makes any sense.
 

Kati

Patient in training
Messages
5,497
@Kati - Rituximab primarily targets CD20 on B-cells. I'm pretty sure that monocytes do not express CD20 - I've never heard it mentioned to the best of my knowledge. Rituximab is generally viewed as selective for B-cell depletion. It's used in B-cell cancers as well (not myeloma though, as it doesn't work).

So if it's one of the 2, it's probably valcyte.

I'm inclined to think much of the benefit of valcyte is in the immunosuppressive effects, which are generally viewed as negative side effects - but who knows, it could actually be useful as an antiviral - or even through both mechanisms. Maybe if I looked at some of the Montoya studies through that lens I could figure out if that makes any sense.
Yes, right. Valcyte, not Rituxan. Brain is like jello.
 

5150

Senior Member
Messages
360
if you have more than one person in the family with CFS, perhaps you might want to get tested for Lyme

hi Daff, is this implying that Lyme is contagious? why check it , if the CDC says it's 'maybe' contagious only through sexual contact? That isn't happening in Families that I know about. Anyway, can you please explain what you mean, so I can stop thinking about it? Thanks
 

SOC

Senior Member
Messages
7,849
if you have more than one person in the family with CFS, perhaps you might want to get tested for Lyme
Been tested for Lyme and came up negative. I don't know that the testing is all that reliable, but that's where I stand right now.

The first person in my family to develop ME/CFS was in Incline Village at the time of the outbreak, so he suspects an infectious trigger but not Lyme. Daughter and I were not close enough to him to have caught whatever it was from him at the time. My suspicion is that any family connection is a genetic immune weakness which makes us more susceptible to viral infections, so it's not one pathogen that got us all, even if it's pathogens that are maintaining our symptoms.
 

Eeyore

Senior Member
Messages
595
That's fascinating that you have that connection to Incline Village.

I tend to agree with your interpretation of genetic causation. However, it still strengthens the idea that ME in endemic and epidemic forms is essentially the same pathology - maybe triggered by different pathogens.
 

SOC

Senior Member
Messages
7,849
That's fascinating that you have that connection to Incline Village.
Yes it is interesting, particularly because he didn't live there. He was just there a few days on business and came home sick and never recovered. We all know that story.... So it's unlikely that for him it was something like mold exposure or any long-term environmental toxin exposure.

I tend to agree with your interpretation of genetic causation. However, it still strengthens the idea that ME in endemic and epidemic forms is essentially the same pathology - maybe triggered by different pathogens.
I have no firm belief about causation at this time. I don't think there's enough data. However, my current favorite theory is some kind of multiple-hit. We have a genetic immune weakness that alone wouldn't cause ME, but combined with the wrong pathogen leads to ME. It may not be the same pathogen for everyone, but it may be a limited set, perhaps ones that have a stronger impact on the immune system than others.

By my thinking, people with the same genetic weakness (such as family members) may never get ME if they don't encounter the wrong pathogen. On the other hand, people who encounter the same pathogen but have good immune systems don't get ME. Only those of us who got the double-whammy develop ME. This is not my original idea. It seems to be considered a likely possibility by a number of our top specialists.

I also think it's possible that pathogens perpetuate the condition. It may not be a single pathogen all the time in all of us, but I suspect many of us are almost constantly fighting some pathogen -- whether it's herpesviral reactivations, or enteroviruses, or Lyme, or just recurrent URIs.

I don't have much of an idea about the autoimmune theory. Everyone I know personally with ME has a clear viral presentation -- flu-like symptoms, viral onset, recurrent infections. I don't know any PWME who don't catch anything, so it's hard for me to envision -- not that I'm saying it isn't a normal ME presentation, just that I it's hard for me to really get into that theory yet because it doesn't fit the people I know. I'm waiting for more research to help me understand that particular picture.

Won't we all be laughing (yeah, right) if, when someone finally figures out this damned disease, we find it has nothing to do with pathogens or autoimmunity. :p