Question about JCV Antibody Test

[SonyaK]

Hi!
I'm hoping someone can help to explain more about this test and what the results mean. My neuro asked me to participate in a study where they do this test once a year for three years. I have no interest in taking Tysabri, but the nurse said this test may help with other treatment decisions in the future? (I'm on Copaxone, but have taken Avonex, Rebif, Beta)

So, from what I understood when the nurse was trying to explain, 50% of MS patients will test positive? And testing positive means your body is actively fighting the virus which causes antibodies and you’re more at risk for PML? I thought that 80% of the population have had the JC Virus at some time. But the nurse said the general population (non-ms, etc.) wouldn’t test positive because they have strong immune systems? (at least that’s what I think she was saying?) Do I have this right?

Being the medicine-phobe that I am, I passed on the test for now because I'm scared that a positive result (with my body actively fighting the virus?) would mean that the fear of PML will haunt me no matter which immune-modulating meds I may choose in the future.

Sorry for the long post, and I apologize for probably sounding like an idiot, but I was just hoping someone may be able to shed some more light on this for me. Thank you so much.

[Redwings]

Hi Sonya:

Because of Tysabri, there has been a lot of misunderstanding about the JC virus and PML as they relate to MS. There are many, many people who think that PML is something exclusive to people with MS. In fact, the opposite is true.

There are many organisms that people are exposed to and even carry. Normally functioning immune systems easily keep internal organisms in check and they never cause a problem. It isn't just your immune system "actively fighting" the JC virus. Your immune system actively fights all kinds of bacteria, fungi and viruses all the time. Everyone who has a normal immune system actively fights all kinds of foreign invaders all the time. That's the function and purpose of the immune system.

(As an aside, one of our assignments in a microbiology class was to take samples of everyday objects we're exposed to and culture the organisms. Good grief! I didn't want to breathe, eat or touch anything for about a week after we saw the cultures.)

When an immune system becomes suppressed for some reason, there isn't a check mechanism operating anymore and those organisms can then flourish. As a group they're called opportunistic infections. They take the "opportunity" to multiply when there isn't an immune system to keep them under control. It's a microscopic version of "when the cat's away the mice will play."

The JC virus is only one of those organisms. And you're right, Sonya. An estimated 70 to 80 percent of people have at least been exposed to the virus and many of them carry it, most of them harmlessly. There isn't anything special about MS patients carrying the JC virus.

In her somewhat fumbled explanation, the nurse said that 50% of MS patients will test positive for JC virus antibodies. That's because 50% of everybody will test positive for the antibodies. And the estimate is actually higher -- more like 70%, which is where the estimate came from that 70 to 80 percent have been exposed.

it is NOT true that the general population won't test positive for the virus because their strong immune systems fight the virus. (What garbage!) It's the antibodies that signal the immune system to fight the virus in the first place. The other things that are wrong with her explanation is the implication that the immune system in MS is weak, and that the immune system in MS is too weak to fight to fight the virus and that's why people with MS test positive for the antibodies. (Frankly, you should never pay attention to anything that nurse tells you, ever again.)

The JC virus multiplies uncontrolled ONLY when the immune system is compromised. That happens in people with HIV/AIDS and those whose immune systems are suppressed by medication. Hundreds of immunocompromised people die from PML every year -- we just don't hear about it. Almost none of them have MS.

PML has come to the attention of the MS community only because treatment drugs have moved into the realm of immunosuppression. Tysabri is the med that opened the door to people with MS developing PML. It gets a lot of attention because of its particular ability to deactivate the mechanism in the immune system that normally keeps the JC virus in check. With all else being equal, the risk for PML is the same for anyone taking Tysabri, not just people with MS. But because the MS community hadn't really been exposed to immunosuppressants before Tysabri, somehow that was taken to mean that PML affects only people with MS.

Primarily because of Tysabri, there has been great interest in knowing more about how many people carry the JC virus to try to gauge the risk of them developing PML based on who has proof of virus antibodies and who doesn't. The theory is that people who don't have evidence of JC virus exposure will be at lower risk of developing PML because they might be assumed to be free of the virus that causes it.

Sonya, even if you were to test positive for JC virus antibodies, it's impossible for you to develop PML if you aren't immunocompromised. (If you did, you would make medical history!) The point, right now, of you being tested would be to be part of the study to determine what percentage of the population (right now apparently confined to people with MS, since the focus is on Tysabri for MS) has JCV antibodies. Immune modulating meds don't increase your risk for PML. Only immunosuppression increases your risk. And if you choose to take an immunosuppressant med in the future, you should be aware of your risk of PML.

The one thing the nurse was correct about is that knowledge of the prevalence of JCV antibodies might be helpful later as new medications for MS are developed -- more meds that work by suppressing the immune system. Right now, Gilenya is a question mark. But Rituxan, Cellcept and methotrexate, all of which are being used to treat MS patients, currently carry a PML warning. Campath carries a general infection warning; when it becomes Lemtrada for MS, it will keep the same warnings and might even have a specific warning for PML.

To summarize, if you're not immunosuppressed, your JCV antibody status is irrelevant and nothing to worry about. You will never develop PML if you aren't immunosuppressed. If you want to be part of a study, you can agree to be tested. Otherwise, there's no need to.

[SonyaK]

Thank you so much for explaining this! I was totally confused by what she was saying. I really appreciate you taking the time to help me fully understand.

I’m probably one of the ones who should get tested, because after 12 years since being diagnosed, I continue to get new lesions while on each of several different DMDs. I’m trying to hold out for BG-12, because it’s my understanding that it is not an immunosuppressant, but I could be wrong.

Thanks again for your awesome explanation!

(That assignment you had for your microbiology class would’ve scared the crap out of me!! )

[Hawkgirl]

Wow Redwings! That was amazing!

Well, I'm being evaluated for that antibody because my new neuro thinks I'd be better on Tysabri. She downgraded me to SPMS, so I think she wants to keep me from having more attacks. She told me that whether it comes back positive or negative, we can talk about the pros and cons of doing Tysabri.

[hope32]

Wow, Redwings, thank you so much for that clear and thorough explanation! I was asked to participate in the study at my last appt (haven't gotten my results yet) but I guess I didn't understand that much about it.

[0485c10]

The nurse was partially right, she just got the past/present part wrong. A positive JCV antibody test means in the past you were exposed to the virus. I like Redwings explanation with the larger % than biogen reports have been exposed. There is a conflict between what biogen reports finding in trial and what the national institute of health has found in their trials.

Redwing is right that more drugs than just tysabri can cause pml--the immune suppressants can. And Biogen isn't the only pharma fighting this risk. biogen just has a greater risk than other drugs....there is a coalation of drug manufacture that have come together to find out how to stop the med induced pml, that manufacture a drug with pml as a possible side affect to their med.

there is a trial going on right now for a med that will get rid of jc virus lying dormant in a person, so it cannot be the cause of pml in a person using an immune suppressant med---

you being asked if you would be willing to participate in the study, despite not using a med with a side affect of PML, may just mean they are looking for more control subjects for their studies---not that you are a canidate for a med that has PML as a side affect.

there is that controversy between the gov & biogen about how many people have been exposed to the JCV with the gov studies showing ~7-80% and biogen a showing 50%

when biogen went to the fda to get their jcv antibody test approved the fda pointed out this conflict and wanted an explanation for it.

they required biogen to do a study to find out the % of jcv positive people in the MS population--with all types of MS....it may be that people with MS has some kind of immunity to the jcv that normal people don't have?? Which would explain why biogen got a lower % than the gov has.

Biogen established their % based upon people with RR MS. which is what tysabri treats.
RR people tend to be younger as the longer a
person has ms the greater the likelihood it will go to SP.

In their studies the gov found that the % of people who have jcv rises with age. the longer a person lives, the greater the likelhood that they have been exposed to the jcv.

so that too could explain the conflict in %. Biogen just obtained their lower results with a younger group of people who haven't yet encountered the JCV.

Again the fda required biogen to obtain the % in people with MS, all kinds of MS.

You may have been asked to be in the trial for 2 reasons. they are developing a way tho fight the greater risk of pml with a positive jcv status and being a part of the group of people with MS that the FDA has required BIOGEN to obtain, before they approve the test.