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Anyone with persistent EBV IGM titers that dont leave? CAEBV worries

Eeyore

Senior Member
Messages
595
I think you really need to get more specifics on what happened when they did cytogenetic studies of the bone marrow. Lymphoproliferative disease is a broad category, and can include things from ALPS (autoimmune lymphoproliferative disease) to MGUS or multiple myeloma (and lots of others).

Polyclonal gammopathy is not a particularly worrisome diagnosis in and of itself. It just means you have high levels of antibodies on an SPEP or IFE. If docs don't see a monoclonal band they won't worry. A monoclonal gammopathy means that the high levels of antibodies are not due to general stimulation or immune overactivation but rather due to malignancy. So polyclonal gammopathy, which you have, is much less concerning than monoclonal gammopathy. They look very different when you test for it.

High EBV titers are really not that rare. They don't necessarily mean anything. The numbers you see that they are "supposed" to be are not really correct at all. In EBV negative people, that's what you'd expect to see - but almost no one is EBV negative. It affects probably >99% of the population by adulthood. So most people have numbers many times higher than normal, and that just means they've been exposed, like the rest of the population. Studies have failed to show a difference in EBV titers between ME and non-ME patients, and it is a myth than EBV causes ME (although it seems to be the case that it can be the triggering infection). EBV infection is always chronic and lifelong and there is no cure. Look around you though - if you are in a room with 100 people, maybe 1 doesn't have EBV - and they'll all have tests that show that their antibodies are many, many times higher than "normal" - which actually means versus people unexposed to EBV, which is virtually no one.

It is odd that you are continuing to express high levels of IgM. That's the only thing that really strikes me as peculiar about your case. It doesn't necessarily mean anything about EBV's persistence or activation. You may have some sort of abnormality in immunoglobulin class switching where you don't properly shut down IgM production and transition to an IgG response.

Someone else asked the question but I'm not sure it was clear to you what was asked. Have you had quantitative measurement of your immunoglobulins in general? Not specific to EBV - not an antibody test to a virus. We're talking about a test that will show IgM, IgG and IgA and give numbers after each, the IgM number is often around 100, the IgA is often around 250, and the IgG is often around 900 (very rough averages and people vary a lot). This would help determine if your body produces abnormal quantities or types of antibodies.

I'd like to know more about the cytogenetic abnormalities found. You may have a genetic or acquired immune deficiency or immune dysregulation.

BTW - if you are really concerned about active EBV, you should have a PCR test for EBV done. This doesn't look for your body's reaction to EBV, but rather for the virus itself (actually, its DNA). You might be continuing to produce antibodies not because the virus is present or active but because your own immune system acts abnormally for some reason. PCR distinguishes between active and latent infection, antibodies don't.
 
Messages
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Eeyore! Thanks for your response. This might help
YES- I had the immunoglobin levels tested. All normal EXCEPT the polyclonal IgM - the range in my lab end at about 276 and my levels are only in low 300's so only very mildly elevated. And that has been the case pretty much steady the last 15 or so years.

YES- I had blood PCR which was negative. Which has me very intrigued, esp. since my titers are climbing. I am wondering if what this whole thing is is some autoimmune response to the ebv in my body that never leaves, i.e., the disease is inactive but my body thinks it still is..... But I don't fit criteria for ALPS. I do however have the ANA, anticardiolipin antibodies and my RA is just about ready to trigger positive (its a 13, at my lab 14 is it). I was just to about to post the question, "Why are my symptoms more autoimmune than chronic ebv" Meaning, I have no swollen glands, no fatigue, no fever, none of the usual reactivating mono stuff. Mine is more of like an autoimmune collection - head neuralgias, arthralgias, nerves, twitching. And every medicine I take - even early on the psych drugs they were saying would help because clearly this was all in my head (ha ha)- I have a pardoxical reaction to.

I am showing CMV titers as well, and I may have mentioned that. Also, unsure where I am with the Lyme still....

As for the cytogenetics result, it showed a del4(q21-35) on 3 of my 20 cells analyzed in the bone marrow tissue. It says "consistent with lymphoproliferative disorder or plasma cell dyscrasia." I am wondering - since it was done while I was in the midst of my very first "flare" - if what it was capturing was a reactivation. Or, would this show up in anyone who ever had a bad case of mono (like me). I don't know. Maybe the EBV DNA is in my bone marrow- I would guess yes, and probably if they did PCR on it (they didn't then) they would have seen it. What the implications are, I don't know - all my blood counts are pretty much normal. No alarming "B" symptoms of night sweats, fevers, lymph glands, fatigue, anemia.

Its a medical mystery. Lets see what the hem/onc says. Hes the one who drew the bone marrow and cytogenetics 15 yrs ago so Im hoping hes still interested enough now that we know it was EBV.

I really thank you all for your insightful comments.
 
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60
Oh, and just to add one more thing to the above, its almost like Im in a constant state of serum sickness. Everything medication seems to cause it. Every flu shot, every vaccine. I was actually feeling better around Christmas despite having the flu and bronchitis (with no recovery problems from either so my immune system can't be that bad), but then had the flu shot and a round of heavy duty amoxicillian for dental work - after that started to feel horrible. Hives and food allergies which I never had in my life, etc. This lasted for months. Then I started Valcyte and all the head and particularly throat neuralgias started. So hard to distinguish allergic reaction, from side effect, from herx, etc......
 

Eeyore

Senior Member
Messages
595
@Pyr2 - Well, if your PCR is negative, I doubt you have active EBV to any appreciable degree. During an active phase of infection, you'd see the PCR elevated. I think that in general your illness sounds more autoimmune. RF is raised frequently in autoimmune diseases other than rheumatoid arthritis, and even in healthy people. I wouldn't make too much of it unless you show signs of RA. You can also test ACPA (i.e. CCP) - this is an antibody to cyclic citrullinated peptide, and it is frequently found to be elevated in RA. Neither is a specific finding though, and diagnosis of RA requires evaluation of both clinical and lab markers. You also want to test for inflammation (ESR and CRP). Another, newer, test used for earlier RA is 14-3-3 eta protein - it's often elevated before the others, but is newer and many doctors don't know much about it. I don't think your RF of 13 is indicative of RA from what you are describing. You frequently find much more elevated RF in perfectly healthy people. If your inflammatory markers are negative, and your ACPA is also, I think it's very unlikely.

I wasn't suggesting you have ALPS, only giving an example of a lymphoproliferative disease. They can be autoimmune, but they are often due to somatic mutation.

The symptoms you're describing do not sound like an active viral infection. Your reaction to vaccines, for example, suggests an autoimmune component is more likely (especially given the negative PCR). Antibody titers do not measure virus activity. There is some loose correlation probably, but you cannot make any solid inferences about viral activity based on changes in titers (other than seroconversion, when a person goes from negative to positive). You can sometimes, at best, make educated guesses.

The twitching is an interesting symptom - this implies motor neuron involvement. I have had this too, off and on, generally when it happens it happens for months at a time and then goes away... and then eventually comes back. I've had it start the day of a vaccination. I think this is probably due to some kind of generalized immune effect where all antibodies are increased, and among those there is probably an antibody that is causing your neurological symptoms.

Valcyte is a pretty serious drug, and I'd be hesitant to use it unless I had documented infection. It can have serious side effects. In commonly used doses, valtrex (different drug) is pretty safe, although not quite as effective on EBV or other gamma herpesviruses. If your doctor thinks you need it though due to active infection, the valcyte might make sense. It's definitely possible that some of your symptoms are from that - it is a drug with many side effects. Don't stop it w/o talking to your doctor though - I don't know enough about why you are taking it, and I'm not a doctor! I tend to react poorly to some psych meds (in particlar, low dose TCA's, which are supposed to help ME patients, but I can't tolerate them at all).

A plasma cell dyscrasia refers to the B-lymphocytes (cells which make antibodies). Mature B cells are called plasma cells. So you have a somatic mutation in a B-cell. This frequently results in something called MGUS, or monoclonal gammopathy of undetermined significance. The particular deletion you have is not one of the common ones that I know anything about (there are certain deletions, like q13, that delete certain tumor suppressors and are frequently found in certain cancers, but deletion of the short arm of chromosome 4 doesn't ring any bells for me). What I found from some quick googling was info on germline mutations, but yours is not germline, it's somatic (or you'd have 20/20 cells with it). This means that at some point in your life, a cell mutated, and kept dividing, so all of the cells that are descended from it have the same abnormal genetics. This can be a precursor to many blood cancers, but most people who have MGUS don't develop blood cancers and in fact never even know they have it. I don't think del4q is a high risk deletion, but I'm not that familiar with it.

You really need to have an SPEP and IFE done (serum protein electrophoresis and immunofixation electrophoresis). You should also have your serum free light chains checked. You should have a metabolic panel to check kidney function and possibly a UPEP (urinary protein electrophoresis) to look for monoclonal components in your urine (bence jones proteinuria). These are all tests for pre-malignant or malignant conditions like MGUS (again - even if positive, it's usually not a serious problem, but does need to be monitored).

Your neurological symptoms, combined with the elevated IgM, suggest to me that you also need a workup for monoclonal proteins that could target nerve cells. Anti-MAG (myelin associated glycoprotein) IgM should be checked. This is a monoclonal antibody of type M (always M for some reason, not sure why - not sure anyone knows why). You should also have antibodies to gangliosides checked. I would talk to both a hematologist and a neurologist. The fasciculations (twitching) probably merit an EMG (electromyelogram) or NCS (nerve conduction studies - like an EMG, but with stick ons rather than needles). It doesn't really sound at all like degenerative motor neuron disease - it sounds much more like some type of antibody mediated MGUS kind of syndrome like anti-MAG. The fact that you do have a clone already makes me think you need the workup. Your IgM is not very high though, which suggests the m-spike, if present at all, is not very large. It may be a non-secretory clone, which means it doesn't make antibodies.

I would be surprised though if your hematologist didn't run an SPEP already - although IFE is more sensitive and newer, as are serum free light chains. They don't generally do a bone marrow biopsy before an SPEP!

EBV can infect B-cells and is known to cause mutations in some cases, so it's not impossible that that is what happened with you - but it's also very possible that it just happened randomly. There is always a randomness to somatic mutations. Also, Valcyte has been shown to cause mutations in animals, so considering you already have a monoclonal dyscrasia, I'd only take it if there is strong evidence for an infection that it is treating.

I wouldn't be too panicked, but I do think that what you are describing merits a more thorough workup from a hematologist and a neurologist.

One last thing - the word herx is WAY overused. Be careful whom you listen to on this. People take all kinds of meds for infections and then if they get any symptoms at all they think it's good because it means the med is "working" and call it a herx. There is such a thing as a herxheimer reaction, but it's not nearly as common as people describe, and is generally associated with bacterial infections, especially spirochetes like the bacteria that cause syphilis and lyme disease. A true herx happens within a few hours of taking a drug and is short lived. If you're sick for weeks or months, that's not a herx. You don't get a herxheimer reaction from treating a virus. If you have lyme, and take antibiotics, you could get one.
 
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Messages
61
Hello Pyr,

I suggest getting blood testing for Human Herpes Virus-6 as it is the only one which makes sense according to all of the data you provided. It is well known to be an infective agent causing an autoimmune reaction and Multiple Sclerosis in some people.

http://emedicine.medscape.com/article/219019-overview

"Human herpesvirus 6 (HHV-6) was the sixth herpesvirus discovered. Isolated in 1986 during attempts to find novel viruses in patients with lymphoproliferative diseases, HHV-6 is now recognized as a T-cell lymphotropic virus with high affinity for CD4 lymphocytes.[1, 2]
A beta herpesvirus (like cytomegalovirus [CMV] and human herpesvirus 7 [HHV-7]), HHV-6 comprises 2 forms, A and B; as of 2012, HHV-6A and HHV-6B are officially considered distinct species rather than variants of 1 species. HHV-6B causes the childhood illness roseola infantum, whereas HHV-6A has been isolated mainly in immunocompromised hosts. Specific manifestations of HHV-6A infection are still undefined. However, both HHV-6A and HHV-6B may be pathogenic in the settings of transplantation and AIDS. (See Pathophysiology and Etiology.) "


http://www.jacobteitelbaum.com/heal...ons-treating_hidden_viral_infections_cfs.html

HHV-6

"A reactivated HHV-6 viral infection is present in many patients with CFS. A study in the Annals of Internal Medicine found 70 percent of patients with CFS had active HHV-6 infection.42 In another study of HHV-6 in CFS patients, 89 percent with very high HHV-6 IgG antibody levels of 1:320 and above were found to have active infections by cell culture. To compare, most healthy adults with an old, inactive infection have levels of 1:40 to 1:160. Though not all of the studies were able to document the infections, as CFS expert and Harvard Professor Anthony Komaroff notes in his recent review "the great majority of studies have found evidence of active replication of HHV-6 more often in patients with CFS than in healthy control subjects."43

When HHV-6 is present, it seems to affect the immune system's natural killer cells that are critical in fighting infections and are also often malfunctioning in CFS. Natural killer cell function is described in what is called lytic units—which means the ability of cells to lyse, or break down, foreign invaders. An average person has a lytic unit level of 20 to 250, with over 80 percent of healthy people having more than 40 units. However, in people with CFIDS, the mean natural killer lytic unit level is just 12 units. With your immune system so low, the reactivated HHV-6 can then also cause reactivation of the Epstein Barr virus. In addition, both HHV-6 and EBV can suppress immune function, and HHV-6 can suppress your body's ability to fight fungal/yeast infections as well.
Until recently, there was no readily available treatment for HHV-6. Even though it is related to other herpes viruses, HHV-6 is resistant to acyclovir (Zovirax), Valtrex, famciclovir (Famvir), and the other antivirals that are commonly used for herpes infections. Fortunately, there is a new and promising oral antiviral called Valcyte that has been shown in early studies to be very beneficial in CFS patients who have both HHV-6 and EBV viruses. Unfortunately, this drug can have significant side effects, although it causes no problems in most CFS patients, and is very expensive. If you have an open-minded doctor and are interested in exploring Valcyte treatment, the information in the Sidebar 2 may be helpful to your physician."

http://www.formatex.org/microbio/pdf/pages788-793.pdf



"Human herpesvirus 6 (HHV-6) is known since 1986 but the clinical disease exanthema subitum was
described already in 1910. HHV-6 is a typical herpesvirus and also has the characteristic herpes group
features, latency, tendency to reactivations, and neurotropism. In addition, it has an intriguing property to
modulate immune response and to interact with other viruses, and alter their natural course. The spectrum
of diseases associated with or caused by HHV-6 has been enlarging; especially neurological
complications are increasingly reported.
The diagnosis has proven problematic, both in regard to serology and molecular techniques. The two HHV-6 variants, A and B, differ in many respects. Due to encephalitis and chronic diseases, first of all MS, therapeutic regimens are needed. For these reasons, we have concentrated in HHV-6 already for years and reached small pieces of the viral behaviour."


Abdulrahman
 
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