A Hungarian virus study on MM and MGUS patients…

As I announced last week, I’ve finally decided to tackle the possible virus connection topic that we began discussing seriously last fall (boy, time does fly, doesn’t it?!!!) here on the blog. Back then I received many “viral” messages and comments…so many, in fact, that I simply felt too overwhelmed to do anything with them. I tried, but my brain kept going into shutdown mode. I had to give up finally and look at other topics…

Oh, it wasn’t just the messages, mind you…I was also overwhelmed by all the virus connection studies that are still sitting inside a file on my desktop. To be honest, I still feel a bit overwhelmed, but okay the time has come to stop procrastinating, to sift through this rather daunting mountain of information and try to figure out if there could be a pattern or something that might be useful to us…

I need to do this slowly, though, in order to retain my sanity. So it’ll take some time to get through all the material and organize my thoughts and your comments (Note: new virus connection comments are welcome…). Uhm…please put on your patience hat… 🙂

I’ll begin with a Hungarian study published in 2006. As luck would have it, the full shebang is available online: http://goo.gl/Ot37F This is great, since you can read it, too, and see if I’ve missed any important bits or misinterpreted the data etc.

These researchers tested 69 MM patients (48 in stage III, 21 in stage II) and a smaller number of MGUS folks (16 with MGUS and 10 with Waldenström’s macroglobulinemia) for the presence of four herpes-related viruses, as follows:

  • Epstein-Barr, which I myself contracted toward the end of my grad school period (and, if my memory serves me right, I also had mononucleosis in my last year, undergrad, at Harvard; I don’t have those  medical records anymore, unfortunately, but I remember being quite ill at one point and going to the student health service center…).
  • Cytomegalovirus or CMV (I have a good story there, but that’s fodder for another post…).
  • Two herpesviruses: HHV-6 and HHV-8, which (the latter only!) has been associated with the development of multiple myeloma.

More on HHV-8: this virus has also been implicated in the progression from MGUS to MM. Hmmm, I don’t think I knew that…

The control group consisted of 44 patients with non-Hodgkin’s lymphoma…Now, I confess that this part puzzled me…Why use NHL patients? There is no explanation for that. I can only surmise…I must admit that my lack of a scientific background irks me at times like these…

At any rate…these researchers discovered that the most common virus present in the bone marrow and blood both of the MGUS and MM group was, TA DAAA!!!!, Epstein-Barr or EBV. Yes, it turned out that more than half the patients had had EBV at some point (indeed, some were actually in the acute phase of the EBV infection at the time of the study). So they conclude (see abstract) that:

  1. since 13 of the HHV-8 positive MM patients also had an acute EBV infection and
  2. since there was nothing similar in the control group, then
  3. in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.

Pathogenesis (I had to look this up) means “the mechanism by which the disease is caused.” Aha. This was the most interesting part of the study for me, especially given what I mentioned above, i.e. that I almost certainly contracted mono in college and then, less than ten years later (while working toward my Ph.D. at the University of Toronto), I tested positive for EBV…I had a recurrence, it seems. So…could EBV have been my trigger or one of my triggers? Notice, in Table 2, that more than half the folks in the NHL control group also tested positive for EBV…Is this just a coincidence? Oh how I wish this study had had a healthy control group, too…

Well, it didn’t, so let’s fast forward to “Results.” As mentioned above, more than half the MM folks tested positive for EBV, also known as HHV-4; however, the difference between the MM and the control groups was only significant for HHV-8. Oh. Okay.

As for the MGUS folks, I thought it was interesting that nine (out of sixteen) had EBV antibodies. Again, more than 50%…

Interesting excerpt: In the history of HHV-8 research, it has been exceedingly difficult to obtain lymphoid cell lines (e.g. effusion lymphoma) devoid of the EBV genome (Renne et al., 1996; Said et al., 1997). This raises the issue of a possible interaction between these two lymphotropic herpesviruses, at least in diseases of the lymphoid system. Could that have been the reason for choosing the NHL control group?

So what’s the bottom line, here? Well, there certainly seems to be a potential association of MM and HHV-8. But there is more. The final sentence in the study reiterates the final sentence in the abstract: The data also indicate that in addition to HHV-8, the transitional reactivation of EBV may also play a role in the pathogenesis of MM.

Personally, I think there must be something to the EBV connection…perhaps not for all MGUS, SMM and MM folks, but for a subgroup, anyway…

UPDATE #1: Even though it’s early in the game, I thought this “viral” business deserved to have its very own Page (I stuck it right under “Myeloma triggers”). This will make it easier for those interested in this topic to read about it: http://margaret.healthblogs.org/life-with-myeloma/what-is-multiple-myeloma/mgus-to-mm-progression-sox2/myeloma-triggers/virus-connection-to-myeloma/ 

UPDATE #2: Thanks to Hanna for this National Center for Infectious Diseases summary of EBV: http://goo.gl/LXMZA

2 Comments

  1. My pre-SCT blood workup showed that I have the EBV antibodies. I never had the classic symptoms, as far as I know. It’s hard to say. I was the kind of person who worked 16 hour days, 7 days a week. I ignored any symptoms, for sure, if I had them.

    The tests didn’t reveal any HHV or CMV. Just the EBV.

    Some years ago, I attended a LLS lecture in which the speaker mentioned EBV as a possible cause of some types of leukemia.

  2. Wow!!!! I had mono when in college and it took me a very long time to recover. After it I never felt as energetic and as well as before. I have fibromyalgia and had no symptoms before it. I am very interested in their future studies.

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