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Extremely high B cells (CD19) - what's going on? Help understanding results

Discussion in 'General ME/CFS Discussion' started by Antares in NYC, May 13, 2015.

  1. Antares in NYC

    Antares in NYC Senior Member

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    Hi everyone.

    I just received the results of my latest lymphocyte panel tests from two weeks ago, but I don't get to see my CFS doctor in a few weeks. Some of the numbers are truly whacky, so I would really appreciate it if someone could kindly explain to me what this means.

    Here you have the most dramatic results from the panels, and their reference numbers:
    • Absolute CD19 cells: 1061 (110 - 660 cells/mcL) High
    • Absolute Lymphocytes: 3898 (850 - 3900 cells/mcL) Borderline High
    • % CD8-/CD57+ Lymphs: 1.6 (2.0 - 17.0 %) Low
    • Abs. CD8- CD57+ Lymphs: 35 (60 - 360 /uL) Low
    The rest of the numbers in these panels look somewhat within reason. These numbers Iook weird. What can you guys infer from these results?
    Thanks in advance.
     
    Last edited: May 13, 2015
  2. halcyon

    halcyon Senior Member

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    The obvious thing to be worried about with an elevated CD19 count would be B cell lymphoma, but that's not the only cause of B cell lymphocytosis. One of Lipkin's previous findings in ME patients was evidence of clonal B cell expansion.

    Have you had a recent measurement of immunoglobulin levels? How about plasma electrophoresis? Is this result vastly different from any previous lymphocyte subset panels?
     
  3. Antares in NYC

    Antares in NYC Senior Member

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    Hi Halcyon,

    The same test produced the following immunoglobulin (G, A, M) serum numbers:
    • IGG Serum : 912 (694 - 1618 mg/dL)
    • IGA Serum: 220 (81 - 463 mg/dL)
    • IGM Serum: 117 (48 - 271 mg/dL)
    Not sure about the plasma electrophoresis. How should I identify that?

    I don't have previous references for CD19, but both my percentage and absolute CD8-CD57 lymphs are even lower than they were before. Let me know how much I should worry... :thumbdown:
     
  4. halcyon

    halcyon Senior Member

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    That is the name of the test, or it might be listed as SPEP. If you haven't had one they'll probably want to do one now, though I'm not 100% sure it's indicated with normal IG levels.

    I would say not to worry much at this point. Your doctor may not even think much of it, but perhaps a referral to a hematologist might not be a bad idea.
     
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  5. Jonathan Edwards

    Jonathan Edwards Senior Member

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    It is difficult to advise specifically without knowing the full clinical situation but my first comment would be that B cell numbers vary widely in normal individuals and it is much the most likely that you are simply someone who has high circulating B cells. The first thing I would suggest is simply repeat the test because it might be a lab glitch. I would also ask for a blood film to be looked at to see if any of the lymphocytes look odd. A blood film used to be absolutely routine for an full blood count but may not be these days. Protein electrophoresis is unlikely to show anything if immunoglobulins are normal (which they are) and ESR is normal but it would be something to do for completeness.

    I think it is unlikely that the B cell count is anything to worry about but checking over these simple things would be sensible. I do not think the CD57+ count is of any major significance.
     
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  6. Antares in NYC

    Antares in NYC Senior Member

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    Thanks for taking the time to review the numbers, @Jonathan Edwards and @halcyon. My most recent sedimentation rate was 2 (reference 0 - 15 mm/hr).

    Last time I had an electrophoresis test done was 8 months ago, so I don't know how relevant it may be now, but for the record it was 6.9 (reference 6.7 - 8.6 g/dL).

    One thing that's different is the iron infusions I had in recent weeks. My iron and ferritin levels were so extremely low in recent months that doctors recommended two iron infusions to bring it up. The ferritin levels were as low as 9 (reference 29 - 248 ng/mL). That got them worried so we scheduled two iron infusions last month (Feraheme IV packets).

    Hope this extra info helps.

    PS: Jonathan, I have been told that several studies point to low CD8-CD57 as potential telltale signs of ME/CFS
     
    Last edited: May 13, 2015
  7. SOC

    SOC

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    Do any of our medical scientists here understand what is the point of having a reference range if being outside the reference range isn't important? Shouldn't reference ranges be set so that being outside them is likely to mean something other than "It's probably not of any significance"? What's even the point of testing if having abnormal values on the test isn't significant? o_O

    I understand the point that some apparently healthy people might have out of range values, but that should be considered an oddity, not a reason to dismiss out-of-range values in unhealthy people. There has be be more reason than that to consider reference ranges of no particular importance in evaluating test results.
     
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  8. Eeyore

    Eeyore Senior Member

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    The biggest concern with elevated B lymphocytes would be clonal expansion (i.e. one particular B-cell clone has mutated and is now multiplying out of control). However, as Dr. Edwards points out, it's unlikely given normal antibody levels (clonal B-cells make the same antibody and/or light chains, which then form a distinct, monoclonal band on an SPEP). Also, the main thing you look for on an SPEP is not so much the total protein levels, but the pattern. Look for a line that says something about monoclonal bands, or perhaps just "normal pattern" or something similar. That's probably what's going on in your case, but it should be checked into. Polyclonal B-cell amplification usually just means immune activation, and possibly skewing toward the Th2 humoral response.

    Ferritin often runs low in ME. The iron profiles are rather odd and often do not fit either iron deficiency anemia or anemia of chronic disease. Are your hemoglobin and hematocrit in normal range? Ferritin is just a measure of intracellular iron. It can also (if elevated) reflect sequestration of iron inside cells as part of the inflammatory response, but yours is not elevated. I do not think this is particularly odd for an ME patient provided your hemoglobin and hematocrit are normal (or even high, as often occurs per Dr. Hyde). If those are low then you may be iron deficient and you might want to speak to your doctor about supplementation.

    Your sed rate is low, which in healthy people is considered normal. Inflammation often (but not always) increases sed rate. You may want to have fibrinogen levels checked. Sed rate is often low in ME, and one possible reason is depletion of fibrinogen. Sed rates are usually elevated quite dramatically in B-cell neoplasms that produce large amounts of monoclonal antibodies, again making this less likely.

    CD57+ cells are generally either T-lymphocytes or NK cells. Yours appear to be low in number. I don't know why. Elevated levels can be worrisome and associated with neuroendocrine tumors, but lower levels are pretty nonspecific. About the only thing I would even venture to guess at is that they reflect a shift away from Th1 to Th2 immune polarization, meaning your cellular immunity is relatively impaired and your humor immunity is relative upregulated - but that is pretty speculative and would require a lot more testing - and even then, not much anyone can really do about it unless some well understood cause is found. This is something that is observed in ME (not so sure about the counts, but the immune polarization towards the humoral).

    So there are some things you should talk to your doctor about and follow up on, but I wouldn't regard it as something very alarming. It's probably reactive or due to immune dysregulation associated with ME. If your doc saw something really alarming when the bloodwork crossed his/her desk, he/she would likely get you in ASAP.
     
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  9. Kati

    Kati Patient in training

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    i think lab results need to be evaluated in taking a good look at the big picture, compare with the clinical presentation and hopefully evaluated by physicians knowledgeable and competent in their specialty areas.

    for instance, is a GP competent enough to determine the high value of circulating B-cell is nothing to worry about and that a repeat testing in a month will be sufficient? (i am not saying he should or shouldn't here, it's just an example)

    @SOC I see a lot of people worrying because their WBC is 0.1 point lower than normal. The big picture is that the number of circulating WBC cycles from the low range to the middle range all the time. I also read of people who say that a potassiom at 3.7 is low normal and start taking potassium supplements and yet it may well be their normal and represent homeostasis. Potassium supplementation is a tricky thing. Getting too much is not necessarily a good thing.

    I think getting it retested is a good strategy, and chances are it will return to more normal ranges next time (should there not be other worrisome symptoms which would add to burden of suspicion)

    Physicians would need to be aware when lab values represent situations which are alarming. Unfortunately it has been my experience that if patients are not keeping track of their issues, lab values, and lack of actions from their doctors, things get missed on frequent basis, at least for me.

    And then there is the case of my doctor who didn't want to test my hormone levels because 'what is she going to do about it, she doesn't know what it means'.

    Then I thought I was doomed.
     
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  10. SOC

    SOC

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    Yeah, I get statistics well enough to understand that 0.1 point below reference range is probably not a big issue, especially if it's a single data point. :) I'm wondering more about cases where the results are very clearly well out of range, but are not considered significant. Case in point, @Antares in NYC's absolute CD8- CD57+ count above. It appears to be well out of range, but it looks like the doctors are not concerned.

    The human body is a highly dynamic system, so I can see it's possible to get a single data point out of range occasionally without it being significant. The problem is that the conclusion often isn't, "Let's retest that" or "Let's run another test to see if that gives us more information", but instead is "That's probably not significant" without any follow-up or justification for dismissing the out-of-range value.

    I agree that a big picture is needed. A single data point tells us very little. The question is: Are the doctors looking at a bigger picture, and if so, why don't they say so instead of "It's not significant" without any explanation. What other data are they looking at? Wouldn't they need to do further testing to determine if the abnormal value is irrelevant or not? And, as you say, are the people dismissing out-of-range values sufficiently knowledgeable to be arbitrarily tossing out abnormal test results?
     
    Last edited: May 13, 2015
  11. Kati

    Kati Patient in training

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    i would say that at least in my case doctors are tossing abnormal values because I have this disease which means everything else is not significant. It can be quite a bit of a problem.

    The problems surrounding 'the bigger picture' in our case is that for the most part doctors have never learnt about the immunologic changes and heck, the whole pathophysiology of our disease, including immune aspect, autonomic disregulation, hormonal issues, and so on.

    We all know that Dr Peterson would view things quite differently in the light of our disease compared to a regularly seasoned family doctor who has learned to practice medicine via an iphone app. :bang-head:
     
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  12. Eeyore

    Eeyore Senior Member

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    I do frequently see doctors dismissing tests from ME patients on this forum (not the docs on the forum, but patients on this forum reporting this with their treating physicians). Often, the doctors' decisions are reasonable, but they have failed to communicate this to the patients. Other times, ME patients simply are not taken seriously which is a real disservice to us as a patient community. Unfortunately, doctors look for patterns they were taught to look for in med school - but medicine should be much more than that. Doctors are very highly educated, and they should be able to think and reason. They shouldn't simply know how to recognize some well known diseases. They should be able to look at the whole picture and based on deep understanding of the pathophysiology of disease create a testable hypothesis for what might be wrong. Abnormal values that are not understood or easily dismissed as likely insignificant (e.g. a test a tiny bit out of normal range, when that isn't usually an issue) should prompt deeper thought.

    Of course, we have to actually pay doctors for this as it takes time, which means they need to not be so pressured by insurance companies to see x patients per hour just to keep the practice afloat.
     
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  13. alex3619

    alex3619 Senior Member

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    Ferritin is not a good marker of iron. Nearly all causes of elevated Ferritin for example are not related to iron. Its an inflammatory marker. High intracellular iron, and particularly liver iron, nearly always raise serum ferritin, but not entirely always. Some with super high iron have low ferritin, there is a genetic disorder that causes this.

    What is the most common cause of elevated ferritin? Alcoholism.

    Another common cause is lymphoma.

    Both are more common than hemochromatosis. If someone has two hemochromatosis alleles, and high iron, then ferritin is used as a surrogate marker for iron because its an easy test.

    Ferritin cannot be interpreted in isolation. It has to be interpreted in conjunction with additional tests, and sometimes requires a liver biopsy to be sure.
     
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  14. Kati

    Kati Patient in training

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    Physicians also have protocols to abide to.

    For instance in my province, TSH to diagnose thyroid disease is the only thing that can be ordered. If it is out of range, then the other tests can be ordered (I believe it's free T3, free T-4) If you TSH is in normal range and you are showing signs of hypo or hyperthyroid, you are out of luck.

    ESR is not a covered test under the provincial plan if ordered by a GP. It cost 16$ if patient wants it done for any reason, however the patient has to make quite the fuss in order to get it ordered. If it is ordered by a specialist, then it's free. My ESR has ranged from 22 to 38 over 2 years, without my GP raising a finger. (Normal 0-20 in my age range) Most physician shrug when I show my labs. Not significant.


    My province is trying to cut down costs, so they are instructing to reduce the number of tests and imaging. It probably also explains why the Vancouver clinic does not want to get into testing and treating patients with ME but would rather hire allied health care professionals to teach us how to self manage, meditate, pace and eat well by purchasing a cookbook instead of providing sound diagnosis, ruling out other diseases (like the MRI australian study which cohort excluded 2 patients, both of whom presented major structural brain abnormalities- tumor and missing half the cerebellum) and offering treatments which are offered elsewhere in the world.

    We live in a world where there are at least 20 different drug therapies for HIV/AIDs, hundreds for cancer, and so on. Even palliative patients can get all the off-label treatments they want, up to the day they die. But if you have ME, that's a whole different story.

    Pardon my rant. i am in the midst of it.
     
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  15. Kati

    Kati Patient in training

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    So is low ferritin an indicator of inflammation or the opposite? And do you have references?
     
  16. Antares in NYC

    Antares in NYC Senior Member

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    Last month my hemoglobin levels were very low, alongside the extremely low ferritin. That's why they gave me iron infusions.
     
  17. alex3619

    alex3619 Senior Member

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    I have posted on this before. I can get references but its easy enough to search for.

    http://www.racgp.org.au/afp/2012/december/elevated-serum-ferritin/

    Ferritin is an inflammatory marker. Iron is one of many causes.

    See also: http://www.wjgnet.com/1007-9327/12/5866.pdf

    PS Its perhaps more accurate to say that ferritin is a marker of highly altered biochemical function rather than inflammation, and can include oxidative stress. However perusal of all the disorders shows that increased inflammation is typical of almost all of them. I mean inflammation in the broad sense, not the sense of vasodilation and increased immune infiltration.
     
    Last edited: May 13, 2015
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  18. Kati

    Kati Patient in training

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    Interesting, however not relevant in my case. my hemoglobin is at the top of normal range, with usually surplus of absolute Red blood cell count, and my iron stores are very low, I believe my ferritin was around 5 last time we checked. My GO dr is not worried (of course). i swear I am full of inflammation (but swearing doesn't count)-(I am also on a daily ferrous sulfate tablet- otherwise I do not maintain my hemoglobin and my diet usually contains 50% of daily recommended dose.
     
  19. Antares in NYC

    Antares in NYC Senior Member

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    Add Lyme to that equation. Lyme and ME/CFS get patients get squat. They seem to be forbidden, ignored, politically incorrect or inconvenient illness.
     
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  20. Eeyore

    Eeyore Senior Member

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    @Kati

    It's somewhat different in the states. We don't have a single-payer healthcare system, so many people have insurance which allows docs to do as much or as little as they deem medically necessary. Some testing requires prior authorization, but not usually bloodwork, and I've never heard of a plan that limited GP's like what you describe. Mostly GP's define their own scope of practice. They are often busy though, so won't get into things that are too elaborate (they aren't paid well enough for long complex cases) and they rapidly refer out.

    Ferritin is considered an acute phase protein, meaning it is a marker of inflammation and rises early. The logic is that cells sequester iron intracellularly bound to ferritin so that bacteria are denied access to it, which slows growth (unbound iron causes substantial oxidative stress, so it's transferred throughout the body in transferrin and stored in ferritin). Of course the body doesn't think logically, but this is why evolution evolved to treat ferritin this way.

    You should check out some of Dr. Hyde's writings on the subject. The big book he published a while back is now free for download as a PDF and still has some very interesting observations in it. One thing he noted was that ME patients frequently have extremely low ferritin, but hematocrit that is near the top or above the upper limit of normal. This is not a normal pattern. Low ferritin would generally be associated with the opposite - low crit / hgb. It's a rather odd pattern that is seen in ME and POTS as well - you can find a decent number of studies on ferritin levels in both if you look around (e.g. pubmed).

    I'm not sure if the low ferritin of ME should be supplemented. Some studies have shown benefit I think - but many patients do not see much increase in ferritin, just an increase in extracellular iron, which isn't really something you want (above the ref range). It also may be going to the liver - when you check ferritin, you are checking ferritin in blood cells normally. It's not clear how well this reflects liver stores.

    Interesting, both @alex3619 and I are carriers for hemochromatosis. My ferritin is generally low when I'm relapsing badly, but moves more toward normal when I'm feeling somewhat better. I do not think the ferritin is causative, but I can't prove it either way and can't be certain. I think that, for me at least, it serves as a good marker of the state of my ME (mine is relapsing / remitting, without any clear pattern of deterioration or improvement over decades).
     
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