A question about accuracy of an antibody test

[omerbasket]

I watched the following presentation today, which I found facsinating, regarding many aspects of ME/CFS research. The link to the presentation is:
http://www.masscfids.org/videofiles/Komaroff/Komaroff.html

It takes a while for it to open up, but it does at the end... :Retro smile:

Now, my question is about something that he talked about and can be view instantly if you'll press the row that says: "34 - XMRV (Retrovirus) inc CFS (2)", down on the left side.
There he shows a table that shows how many people were tested for XMRV by each of the 4 methods by the WPI, and every time, how many of them were positive for XMRV. Besides the fact that it is the first time, I think, that I see that WPI also tested some of the healthy controls (although not all of them, not even close) by these methods (and all were found negative for XMRV), the thing that interests me is the following: By PCR, 67% of the tested subjects were found positive for XMRV. By viral protein expression, 63% of the tested subjects were found positive for XMRV. by infectious virus in the plasma, 83% of the tested subjects were found positive for XMRV. And, by antibodies to virus in serum, 50% of the tested subjects were found positive for XMRV. Now, at least for the unaware viewer, that would seem as if the serology test is the least accurate one - and that is in oppose to the feeling I previously got that it would be the most accurate one.
However, I guess there very well might be other explanations for that. Perhaps the 18 subjects that were tested for antibodies had the biggest group of people that were negative for XMRV by all other tests?
Or, perhaps WPI is actually saying that the antibodies test is not the most accurate one, but it would give more accurate results when it is combined with the culture test - as oppose to the results we would get from culture test alone? Or, could it be that the antibodies test that WPI did for this study, which was published almost 8 months ago (and the tests were probably done before that) is, actually, the least accurate method - But the method that VIP Dx developed for antibodies test would be the most accurate?

If someone has some insights about that, I'd be glad if they could be shared.

 

[Daffodil]

a british doctor told me an antobody test would not be accurate but i have no idea why...i didnt understand his explanation.

the WPI is now testing for antibodies against more than one gene of XMRV so i think it should be pretty accurate...?

 

[Alexia]

I think some people's immune system may not work well so it can't produce antibodies even if they are infected.
If I understood well it would be better to have both the PCR test and the antibody test.

 

[HopingSince88]

My question is 'what type of antibody does the test look for' ? The reason I ask this is that I had tested positive for IgG for gliadin (a molecule of gluten) once, and then after a long period of time that I was not eating wheat, I tested negative...the antibody for gluten disappeared! I don't fully understand the differences between IgA, IgM, IgG, IgE, and IgD. And I wonder which of these types of antibodies the test is geared towards finding. So my question is, if you have an active infection, I would assume that the antibody would show up, regardless of type, but if you contracted the illness a long time ago, but now are partially recovered, do you still have a readily available antibody and does that affect the accuracy of the test?

 

[Hope123]

I think some people's immune system may not work well so it can't produce antibodies even if they are infected.
If I understood well it would be better to have both the PCR test and the antibody test.

This is definitely a possible reason. Nancy Klimas spoke about this back in December in one of her videos.

It's very hard to know, without the WPI disclosing individual subject results, how good the antibody test is. For example, if a fair number of people were negative on the three other tests, but were positive on the antibody test, this might tell us that the antibody test can serve as backup for those negative by other tests.

Another point to keep in mind: antibodies can cross-react -- e.g. an antibody to virus A might also react to virus B. If you find antibodies to A in a patient who has been exposed to A, you might erroneously conclude they've been exposed to B because of the cross-reaction. We don't know how good the techniques used by WPI are to help distinguish such cross-reaction or if cross-reaction exists. (This was a point brought up in the XMRV Kerr paper when talking about they were discussing their own antibody test.)

Really what the researchers need is a gold standard test -- a test which more or less unequivocally diagnoses XMRV infection. Many times, these are specimens from tissue samples, not blood. It will be interesting for someone to adopt the tissue staining methods of Emory with the easy tissue sampling of the German respiratory study and test WPI's 4 blood tests against those tissue sample results.

 

[ixchelkali]

The antibody test may not be the most accurate, for the two reasons already mentioned (that if a person's immune system were already too depressed, it might not produce antibodies, and because of the possibility of cross-reactions), however the important thing about it in the WPI study is that it shows that the other results weren't the result of lab contamination. Lab contamination doesn't produce antibodies in patients' blood. (At least that's my layperson's understanding of it.)

 

[biophile]

a british doctor told me an antobody test would not be accurate but i have no idea why...i didnt understand his explanation.

A doctor or two have told me doing antibody tests on post viral CFS is pointless because CFS is about what happens after the virus is cleared and a positive test result only indicates a previous infection.

 

[lansbergen]

A doctor or two have told me doing antibody tests on post viral CFS is pointless because CFS is about what happens after the virus is cleared and a positive test result only indicates a previous infection.

You say post viral. What makes you think XMRV is cleared?

 

[redo]

Here's the quote from the oroginal paper:

Plasma from 9 out of 18 CFS patients
infected with XMRV reacted with a mouse B cell line
expressing recombinant SFFV Env (BaF3ER-SFFV-Env) but
not to SFFV Env negative control cells (BaF3ER), analogous
to the binding of the SFFV Env mAb to these cells (Fig. 4D
and S6A). In contrast, plasma from seven healthy donors did
not react (Fig. 4D and fig. S6A).

I am glad to see that they've had 0/9 healthy controls test positive. And I hope the test has been improved with regards to sensitivity. It sounds low to get 50% with the antibody test and 67% with the culture test.

 

[Rivotril]

A doctor or two have told me doing antibody tests on post viral CFS is pointless because CFS is about what happens after the virus is cleared and a positive test result only indicates a previous infection.

first I agree with what Lansbergen says in #8. Second, if this was true, then you could say the same about HIV-AIDS? when you are ill and tired and have AIDS, and you test positive by serology on HIV, that would also be pointless then??? Then you can, in many cases, stop testing on HIV antibodies too!
I think antibodies from a retrovirus like HIV/XMRV, which are not found in controls, indicate that there has been something that led to the current state of health, because the difference in antibodies related to healthy persons is very significant.
But I agree that the real causality (i.e. if XMRV is always a condicio sine que non for getting ME/CFS) has yet to been proven

 

[ukxmrv]

VIP dx intend to offer both the Culture and the Antibody test together (or they did last time I spoke to them). They also intend to re-test earlier negtative culture test people.

We can set up some more polls here and see what the results are to help determine how good the new test is.

 

[biophile]

You say post viral. What makes you think XMRV is cleared?

first I agree with what Lansbergen says in #8. Second, if this was true, then you could say the same about HIV-AIDS? when you are ill and tired and have AIDS, and you test positive by serology on HIV, that would also be pointless then??? Then you can, in many cases, stop testing on HIV antibodies too!

It is not my personal opinion that antibody testing is pointless. I was replying to Daffodil's conversation with a doctor. I should have been clearer and added, "The doctor you spoke with may have a similar view as the doctors I saw years ago who were responding to my enquiries about viral testing".

 

[lansbergen]

It is not my personal opinion that antibody testing is pointless. I was replying to Daffodil's conversation with a doctor. I should have been clearer and added, "The doctor you spoke with may have a similar view as the doctors I saw years ago who were responding to my enquiries about viral testing".

Thanks for clearing it up.

 

[JillBohr]

Well, I am confused more than ever. I was looking forward to getting my son the antibody test that is coming out but I now I wonder if I should get tested or my younger son. Perhaps there is a better chance that I have antibodies or my younger son. My oldest son, if XMRV pos., probably has a very active virus with little or no antibodies.

 

[Rivotril]

It is not my personal opinion that antibody testing is pointless. I was replying to Daffodil's conversation with a doctor. I should have been clearer and added, "The doctor you spoke with may have a similar view as the doctors I saw years ago who were responding to my enquiries about viral testing".

okay thanks for that. I didnt really think that it was your opinion, i just think its a strange way of reasoning by some docs.
If you reason like that you can also say, when someone is positive on, lets say culture, and lets say by fiction that the test is 100% sensitive:
"oh youre positive on xmrv? o, so is 4% of the population, so are millions of people who feel great, so it doesnt mean anything"
what i want to say is thats it's always a combination of (latent or active) infection, symptoms (and things like low NK counts/ other infections) and (according to wpi, not yet proven) causality i think

 

[omerbasket]

If you'll watch the whole presentation. you'll see that Dr. Komaroff actually talks about kinds of viruses. He says that there are viruses which your immune system cleans up, but there are viruses that the immune system can just supress, but they stay in the system and some times "wake up". Such virus is the herpes virus that causes herpes wounds near the mouth.

 

[Hope123]

Well, I am confused more than ever. I was looking forward to getting my son the antibody test that is coming out but I now I wonder if I should get tested or my younger son. Perhaps there is a better chance that I have antibodies or my younger son. My oldest son, if XMRV pos., probably has a very active virus with little or no antibodies.

It's important to note that aside from the few numbers in the Science paper, none of us (unless we are an insider with the WPI) really knows what the characteristics or the test are yet and whether/ how many people with CFS will have the antibody. The dilemma many people are struggling with is whether to get the test now vs. waiting for more/better confirmation since many of us have limited funds. I would not dismiss the antibody test yet based on the speculations we have.

 

[omerbasket]

By the way, I wouldn't dismiss it too. I'm just wondering if we don't know some stuff here, which can make the picture clear again about the antibody test as the best test we have so far.

 

[Hope123]

Looking through my old notes, the only other number I have from the WPI study is that of the 33 CFS people in their study with a PCR neg. test, 19/33 (58%) were positive on the antibody test. Pretty close to 50%.

The 9/18 was drawn from the whole CFS group as it reads from the paper, not the negative PCR CFS group. It is not clear from anywhere whether any of the 18 subjects overlaps with the 33. One of the Science critic letters did make a good point about the WPI not writing how did they decide to choose those 18; if it was random WPI should have stated it. If it was not, WPI should have given the reason.

For the PCR neg. 33, the best test would seem to be culture -- 30/33 (91%) were positive by culture.

(My numbers are drawn from 10/2009 CFSAC Peterson talk but I think WPI published these numbers in their reply to Science or on their website?)

Then there is the "95%" figure thrown out by Dr. Mikovits which has not been backed by any real numbers. (This is separate from the Science paper.)

 

[usedtobeperkytina]

Well, now wasn't the study was based on an antibody test they had a year ago. They just announced a couple of weeks ago that they have an antibody test that they feel confident enough to use on the public at large and is accurate.

Or am I getting things confused again?

Tina