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Holy crap -- IgM deficiency

Discussion in 'Immunological' started by SOC, Oct 10, 2013.

  1. pemone

    pemone Senior Member

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    SOC, I have the same test result: Selective IgM Deficiency. Do you understand how rare this condition is? There are fewer than 300 cases in the literature. We are freaks. :)

    What symptoms do you have, and has any doctor connector those to the IgM?

    Have you seen an immunologist to get a more thorough investigation about possible causes for the IgM Deficiency?
     
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  2. SOC

    SOC Senior Member

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    Yup, we're freaks alright. :hug: As I understand it, they can't even figure out how it's possible to have Selective IgM Deficiency, although they're willing to admit it exists since they can test for it.

    I have ME/CFS, of course, which could be connected to SIgMD. I have the multiple infections and reactivations common in ME/CFS. They could be related to the Selective IgM Deficiency.

    My ME/CFS doc is an immunologist. Last time I talked to her about the SIgMD she said there's nothing direct they can do about it. Current practice is to use abx, antivirals, and antifungals to treat opportunistic infections as they arise.

    Sucks to have a rare disorder, doesn't it? Nobody bothers to do much research or develop treatments.
     
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  3. pemone

    pemone Senior Member

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    Do you have high LDL cholesterol? This study bothers me:

    http://circ.ahajournals.org/content/120/5/417.abstract

    Low IgM correlates to development of arterial plaques and heart disease.

    What's quite interesting is that a low related element C1q in theory slows down aging process:

    http://rt.com/news/japan-scientists-stop-ageing-461/

    Unfortunately, in the tests Japanese scientists did, low C1q made the animals susceptible to infections. So they age slowly but are susceptible to disease. Do you look young for your age? I do.
     
  4. maryb

    maryb iherb code TAK122

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    @surethom
    the only way I got a print out with the ranges on from my surgery was by saying I wanted a copy for a hospital visit I had last year. Otherwise you could just ask the GP outright if you could have a complete copy.

    Its just another example of treating the patients like dumbos, aka NHS policy... we can't possibly have all the facts we may question them. I mean its not as if they could interpret the results without the ranges on.
    morons the lot of them.
     
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  5. PhotosByPflanz

    PhotosByPflanz

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    I am afraid that I am coming to this forum a bit late, but I just stumbled across it. I have Selective IGM Deficiency and have been living with it for about 10 years. As you have all noticed, there is not much research done because it is so rare. I have gone through a few different treatment options and so far it has been a roller coaster ride. The low-dose daily antibiotic worked fine for about a year. My body got used to it so we switched antibiotics, but that did not work. It also left me vulnerable because my body was used to it and when I did get a sinus infection, on antibiotics it got progressively worse and ended up as a upper respiratory infection. Even on two different antibiotics, an inhaler, and steroid, it progressed into pneumonia and I ended up in the hospital for a few days.

    I was blacking out when I coughed and found out that my blood pressure medication (beta blocker) was causing bronchial spasms which robbed me of oxygen. After several IV bags of antibiotics, and a change in BP medicine, I got out of the hospital. Recovery took me about 6 weeks to get back to normal. After that I started playing with vitamins. Even on 1000 i.u. daily vitamin D, my blood test showed low D levels.

    I played around for the next year or so and was sick once a month where I needed antibiotics, sometimes 2 or 3 rounds to kill an infection. I bumped the D to 15,000 i.u. and added E, C, and B12 in normal doses. Since then I have been sick to the point of needing antibiotics about once every 5 or 6 months!!

    I have an 8 and 11 year old in school so I get everything brought home. I still get the colds and other bugs floating around, and I still need bacitracin for any cuts to prevent infection, but since doing the vitamins every morning I have been much healthier. Talk with your doctors, but I recommend experimenting with vitamins until you find a balance that works for you.

    The reason I tried experimenting is that my mother has Parkinson's Disease. Average life span is 7 years. She has been living with it for 18 years. She takes vitamins and eats foods rich in antioxidants. This she has done on her own as doctors want to give a pill to stop the tremors, but that makes you lethargic and that is the worst thing for your muscles.

    Find what works for you, but never give up, and never believe that every doctor has the answer. So do, some don't.

    I hope this helps someone.

    Best regards,

    Brian
     
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  6. PhotosByPflanz

    PhotosByPflanz

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    P.S. My IGM level was at 8
     
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  7. pemone

    pemone Senior Member

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    I have low IgM and find I have no propensity for infections at all. The telltale sign for me is that when I do get an infection, I feel like I recover quickly, but in fact that is a false signal, and when IgA kicks in 10 days later I get hit bad. IgM is the initial responder to infection and when you have this condition your initial response is too weak.

    What is the source of your infections? Maybe the hospital environment itself is subjecting you to these? Taking low dose antibiotic 24x7 is certainly going to screw up anyone. It will kill valuable gut flora, make organisms in you resistant to antibiotics, and in general make you feel lousy.
     
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  8. Eeyore

    Eeyore Senior Member

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    @SOC - I'm not sure this is selective IgM deficiency. I can see where you'd get that from looking at the test results, but you seem to just have low levels of immunoglobulins in general. Don't pay too much attention to the reference ranges - they are just to give a rough idea of where most people fall, and you fall at the low end for all 3 subclasses, in some just above the low end, in some just below. That's why your IgG is coming back low on one and high on another.

    Do your lymphocyte subsets look normal, if you've had a lymphocyte subset panel?

    With lowered immunoglobulins, I can see why you might experience more infections and have some of the signs and symptoms of IgM deficiency or immunoglobulin deficiency in general, although it appears mild (some people with severe immune dysfunction have no detectable antibodies - in which case you get to live in a bubble).

    This is a bit atypical of ME, as usually ME is considered a Th2 shifted disease, which means reduced cellular immunity with a compensatory increase in immunoglobulins.
     
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  9. SOC

    SOC Senior Member

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    I agree SIgM deficiency seems unlikely. Are you suggesting that rather than SIgM, my results look more like mild overall Ig deficiency? While I think that is more likely, it's still a bit odd that the IgMs are distinctly low while others are low/normal. As I understand it, IgG or IgA is typically the first to drop, with others following later.

    In what way do you mean I shouldn't pay attention to reference ranges -- that my results are lowish but normal and don't need follow-up, or that all of them being lowish should be something to at least follow up on even though most are in-range?

    My most recent labs, done 7 months after the previous ones and by yet another lab :rolleyes:, show my IgM continuing to decline, while my IgG are still only slightly below range.
    IgG 687 (ref: 694-1618 mg/dl)
    IgM 13 (ref: 48-271 mg/dl)
    IgA 155 (ref: 81-463 mg/dl)

    Only IgG subclass 2 is below range, although 1 and 3 are near the bottom of the reference range.

    So while statistically speaking this is likely not SIgM, it seems to be my IgMs that are the most problematic -- whatever that means.

    My lymphocytes look fine, mostly nice mid-range values. The eosinophils are the closest to low -- 69 (ref: 15-500 cells/microL) -- but still well within range.

    Well, yeah, clearly I'm not bubble girl. :D If I were, even my local docs would be taking my ill health seriously. I agree this is not a severe case. The question is -- is it a moderate case or nothing to bother following up on?

    I didn't realize that. Is there research showing ME to be a Th2 shifted disease with increased immunoglobulins?

    It would be good news to find I don't have ME/CFS. :D Not that I don't like you guys, but I'd rather be in a different club, thanks. I have other immune abnormalities, the most distinct of which is distinctly low, and continually dropping, CD8+ cell numbers. So it's not beyond the realm of possibility that I have an immune dysfunction separate from ME/CFS, but if that's the case we're going to have to find a way to explain very clear, pretty severe, classic PEM.

    The latest step in our efforts to understand what's going on here is a referral to a hematologist/oncologist. I see him Monday. After he does whatever hematologists do, maybe we'll know more. Or then again, maybe not. :cautious:
     
    Last edited: May 16, 2015
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  10. Ema

    Ema Senior Member

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    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.
     
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  11. Ema

    Ema Senior Member

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  12. Eeyore

    Eeyore Senior Member

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    @SOC -

    IgM stands for immunogloblin class M. It's one of 5 heavy chains that can form the immunoglobulin molecules, which are each made of 2 heavy and 2 light (the heavies are of the same type, and the lights are of the same type, and one b cell makes only immunoglobulins of one heavy chain and one light chain, e.g. IgG-Kappa). That would mean immunoglobulin with heavy chain g (or gamma) and light chain k (or kappa).

    So I'm suggesting that you don't have an IgM only problem, but an Ig problem in general (involving IgM, IgG, and IgA to varying degrees). There are many immune derangements. Common Variable ImmunoDeficiency (CVID) comes to mind, although usually the G is more pronounced than the M deficiency - but it's variable... hence the name!

    When I say don't pay attention to reference ranges, I mean view them as blurry lines rather than strict cutoffs. So one lab says you are normal on IgG and the other says you are low - neither is right or wrong. The point is that you are on the low end of normal or high end of low, somewhere in that general range. The precise numbers are not important, and vary by lab, time of testing, and many other factors.

    It is a bit unusual to see IgM be the lowest, although IgM can be highly variable. This is because most amplification of B-cells starts as IgM, and then the cells undergo a class switch to make either IgG or IgA, which are long term antibodies. (IgD and IgE are treated differently and have different roles.)

    I wouldn't follow up on these results if you felt normal probably, but since you don't, I would.

    That's not what I meant by lymphocytes. Eosinophils are actually not lymphocytes, they are granulocytes of the myeloid lineage. All blood cells are either from the lymphoid or myeloid lineage, and eosinophils are of the latter. I was more curious about the lymphocyte subset panel (if you have had one) and how the cells are distributed in terms of percentage and absolute numbers (e.g. CD3, CD19, CD8, CD4, CD56) CD3 would mean a T-lymphocyte, which can be broken down to CD4 (helper) and CD8 (suppresor/cytotoxic). CD19 are B-cells. CD56 are NK cells. (Oversimplified a bit but basically correct.) White blood cells (leukocytes) are all the cells that are part of the immune system (not platelets or red blood cells). Lymphocytes are a subset of these, as are granulocytes (eosinophils, basophils, neutrophils). There are others too - macrophages, dendritic cells, etc.

    By mild I don't mean you don't have important symptoms, only that severe immunodeficiency leads to rapid death, which you have not experienced.

    There's a fair bit of research on ME and Th2 shifts. I don't know that it is usually accompanied by elevated Ig's. However, I've generally not heard of Ig's being depressed at all. Cytotoxic function is usually implicated as defective, which is a Th1 process.

    CD8 cells are part of the cellular immune response (they directly kill target cells via perforin/granzyme and other pathways). That they are low suggests a broader immunodeficiency like CVID rather than just IgM deficiency.

    A hematologist seems like an appropriate place to follow up on this. He may be able to make some sense of it. It would require more testing.

    It may be that ME is rather heterogeneous, encompassing a number of different immune dysregulations, all of which share some final common pathway leading to PEM. Or you may have something else... can't tell from the info we have now. He'll probably start with some blood tests. He might eventually do a bone marrow biopsy, but probably not.

    It might be enough justification to get you IVIG, which generally helps ME patients. Dr. Jay Goldstein used it extensively in his early days and it worked well. We don't really know how it works, but it's a general immune suppressant / antiinflammatory and is useful in many autoimmune type diseases, but is also used in cases of immunoglobulin deficiency. You might get it for the latter but it might work because of the former. Most of the time they will not use IVIG in ME patients because it's too expensive and it's in limited supply (it's a blood product - they pool immunoglobulins from other people and separate out the red cells for those who need transfusions). So naturally, it's in short supply - you can't just make more.
     
  13. Eeyore

    Eeyore Senior Member

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    Also - if your numbers are generally dropping across the board, that is definitely a cause for some concern and should be followed up (i.e. all the numbers are continually dropping, implying some problem with hematopoiesis in general). I don't really see evidence of that so far - but I don't have all the data.
     
  14. Eeyore

    Eeyore Senior Member

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    @Ema - The medical community acknowledges universally that EBV is chronic (it is a lifelong disease in all who contract it). What is not acknowledged is that this is the cause of symptoms in ME. This is because studies on this have failed to show any correlations. If anything, it's more likely that some people have genetic immune deficiency that doesn't do a good job of controlling normal infections that are throughout the population.

    IgG levels can be decreased in general, yet high specific to a given pathogen. We all have IgG (other than rare diseases like SCID). We don't have IgG against specific things until we are exposed to them (or, at least, not very much). When we are exposed, the quantity of IgG we have against the antigen to which we are exposed increases dramatically. Even if you don't tend to make as much IgG as others, if you mount any real immune response, you'll make a lot of IgG to the target antigen and it will show up, which shows that your body has at some point "seen" this antigen, and is prepared to deal with it should it encounter it again. Since EBV never goes away (no herpesvirus ever does), this keeps titers up for life in everyone exposed. The overwhelming majority of the population of healthy US adults would have results flagged as "abnormal" for EBV antibodies, because they've been exposed to EBV and have it for life, and so make antibodies as a result - yet they do not have ME.
     
  15. Ema

    Ema Senior Member

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    I don't think that EBV is *the* cause of symptoms in ME/CFS.

    I've never met a conventional doctor that thinks that chronic viral infections are a problem for anyone. They are taught that if you only have a high IgG level, it is reflective of the past exposure of which you speak and doesn't signify a reactivated infection.

    At this point we don't have a very good way to differentiate between past and chronic, reactivated infections. Only doctors like Lerner are willing to consider that extreme elevations are not just indicative of past infections and are worth treating. His success in getting this subset better proves to me that there is something to this line of thinking.

    I've seen EBV titers go up and down in relation to symptom severity.

    I don't think I've ever seen a "healthy" person with EBV titers as high as is common in our population, especially to the EA.

    I still don't understand how one can make a substantial amount of IgG to a substantial number of different antigens...and still turn up low overall in IgG. If one was only high in relation to one or two antigens, maybe. But all that dramatically increased IgG has to start accumulating at some point. You couldn't have many different bank accounts all full of money and then yet somehow claim to be bankrupt overall. It just doesn't make any sense.
     
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  16. Eeyore

    Eeyore Senior Member

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    The studies just don't support what you are saying. Many studies have looked at EBV levels in ME patients and there has been no significant difference in mean titers or even the rates of seropositivity. I think patients fixate on it because it's the first test they get that is flagged as outside the reference range, even though almost everyone would get a result outside the reference range. The only study I ever saw that really hinted at anything substantive was that ME patients are more likely to have antibodies to the VCA rather than the EBNA - suggesting a defect in cellular immunity (possibly).

    Antibody titers don't move very quickly at all - the half life for antibodies is months. It makes it very hard to correlate with symptoms. It is certainly possible - even very likely - that reactivations do increase IgG levels. This is why we give vaccines in general - after a time, if your body doesn't see an antigen, the immune response will taper off, so you use a booster vaccine to increase memory B cells and circulating antibodies and hence maintain immunity. Herpesviruses are somewhat unique (or uncommon at least) in that they are not cleared ever - so the chronic low grade activity keeps titers up. I do think a large increase in IgG to a herpesvirus versus a baseline in the same individual might indicate a reactivation, but we know this occurs commonly in healthy people too. The problem is sorting out why patient A suffers with ME and patient B feels normal, and both have elevated titers to EBV. I can see where the docs are coming from on this. Without a study, it's plausible to think EBV titers might be higher and that this might signify reactivations, but the studies have been done and no difference was observed (quite a few studies) - so it's not hard to see why the docs feel as they do.

    Regarding IgG levels - let's use some numbers - made up, but correct enough to give the overall picture.

    Say a normal person makes IgG to about 10 million antigens. The total pool of IgG in this person is a combination of all of them. Say we test for viral IgG. Let's say we are very thorough and test for 50 different viral antigens (I don't know of an ME doc who tests this many). Say all of those 50 are elevated. that means 1 in every 200,000 antigens is elevated. Average 1 elevated with 200,000 decreased - and you can probably see why it isn't going to matter much in the whole average.

    I think you might be underestimating the number of antigens we make antibodies to, and just how specific antibodies are. Even against one bacterium or virus, we might make hundreds of different antibodies (or more). Some are higher avidity, and the immune system tends to select for these over time.

    I'm not sure what the actual numbers are but I know they are ridiculously large and antibodies are incredibly specific.
     
  17. SOC

    SOC Senior Member

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    If only insurance companies agreed with you (and me) about reference ranges. I am not currently eligible for treatments simply because my IgG is in range, even though overall my immunoglobulins are low. All they care about is the reference range on one factor. :rolleyes:

    I'm kinda thinking CVID, but again, I don't get that diagnosis because my IgG is still almost in range. So while I don't think it should be, doctors and insurance think it's all about the reference range.
    Well there you see how much I know about immunology. :p
    I'm due for another round of immunology tests in a couple of weeks, but this is my previous data:
    Oct 2014
    Total CD3+ 65% (ref: 66-80%), 812 (ref: 989-1899)
    CD4+ 57% (ref: 38-53%), 704 (ref: 595-1199)
    CD8+ 10% (ref: 15-32%), 126 (ref: 219-731)
    CD19+ 10% (ref: 8-18%), 125 (ref: 120-400)
    CD56+ 24% (ref: 5-16%), 295 (ref: 98-294)

    Oct 2013
    Total CD3+ 61% (ref: 66-80%), 877 (ref: 989-1899)
    CD4+ 50% (ref: 38-53%), 717 (ref: 595-1199)
    CD8+ 10% (ref: 15-32%), 149 (ref: 219-731)
    Total B cells 10% (ref: 8-18%), 145 (ref: 128-400)
    CD56+ 22% (ref: 5-16%), 321 (ref: 98-294)

    I don't see CD5+ counts for 2014, but for 2013 I have:
    Total CD5+ 61% (ref: 68-82%), 873 (ref: 1022-1933)
    CD5+ CD19+ 0.5% (ref: 1.0-9.0%), 7.0 (ref: 15-178)

    Looking back another year, the pattern is consistent -- all these lymphocytes are slowly declining except for NK cells which started mid-range, climbed to high, and have started dropping again.
    I'm expecting more blood tests, although I don't know what kind. Just have to wait and see. Hopefully he'll have some explanations. With Hodgkin's Lymphoma running in my family, it's best to pay attention to abnormalities that might suggest blood cell abnormalities.
    So far, it's not been enough justification for insurance companies, but I may be getting there. There's talk of a vaccine challenge to see if I'm making antibodies (or something like that), but it hasn't been ordered yet. I think we're waiting on the hematologist's report and my next set of immune labs.
     
  18. Eeyore

    Eeyore Senior Member

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    That is a bit of an odd lymphocyte subset panel. Look at the CD19 number - it's at the very low end of normal. This represents B-cells, and B-cells make antibodies. It is consistent with the reduced antibody levels you are experiencing. Your CD4 cells look mostly normal - lowish end of normal range (absolute, not percent). A deficit there would be found in HIV (and other diseases too) and could imply that B-cells aren't getting activated by T-helper CD4's, but that doesn't look like what is going on in you. It seems to be a relative lack of B-cells. Odd also that your CD8 T-cells (cytotoxic) are well under normal range. NK cells are higher than normal, in percentage and absolute. I wonder what your NK function looks like.

    It seems to fit with your antibody pattern, and it does look like it could represent some type of immune deficiency. I do think it's a good idea to see a hematologist. Do you know if you have had an SPEP done? (also called serum protein electrophoresis)
     
  19. SOC

    SOC Senior Member

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    I agree. :) The issue now is to try to figure out what it all means.

    When it was first tested 3-4 years ago, my NK cell function was low, but not as dramatically low as that of some ME patients, including my daughter. For the past couple of years my NK cell function has been high normal to slightly high -- possibly (but by no means certainly) due to some supplements.
    Yep, I think immune deficiency of some type has been an accepted part of my ME/CFS all along. It has not been clear what that deficiency is, exactly. Nothing already named and understood... so far at least. As it progresses it's starting to look more like CVID or something even more unpleasant.

    No, I haven't had an SPEP done, but based on my recent reading, I suspect there will be one in my near future.
     
  20. Eeyore

    Eeyore Senior Member

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    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?
     

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