Positive Antibodies, Negative PCR's

[PhoenixBurger]

To those who have done some research in the studies, journals, etc...

What would your conclusion be for an individual who took medications well-known to cause Immune Reconstitution Inflammatory Syndrome (IRIS), but usually only in individuals who were immune-compromised prior to taking them.

Flulike symptoms and neuromuscular/nerve problems developed for 8 months after. MRI, EMG, and all bloodwork normal. Repeatedly. No elevated white blood cells. Nothing.

Except: CD8 Levels high. Pro-inflammatory immune markers low. Anti-inflammatory markers very high. Lyme Disease, Cytomegalovirus, and HHV6 and Epstein Barr antibody tests all positive and *acute* (IGG/IGM).

But: All PCR testing for all the above: negative.

Lyme C6 Peptide, Western Blot, and PCR: negative. Twice.
CMV PCR negative: Three times over a 1 year period.

All testing to actually confirm the presence of these viruses, came back negative.

Those familiar with IRIS know there are different forms, but one includes the immune system "mistaking" past infections as currently active, and mounting an immune response (IGG/IGM) to fight them off.

Discussions with physicians fruitless. One ignores the negative PCR and wants to treat the infections anyways. Others see the negative PCR's and confidently declare there is *no* current infection. And despite the fact that this clearly paints a picture of a confused immune system fighting off past infections (Classic IRIS), all physicians agree that it is impossible to experience IRIS without an immune suppressing disease like HIV.

Special note: Other individuals who have taken the exact same medications, have ended up with diagnoses like GBS, CIDP, Sarcoidosis, and unexplained inflammatory immune conditions.

What is your take on the positive antibody test and negative PCR's in this setting?

 

[vamah]

I can't speak to the other things, but I know that hhv6 is hard to detect in a pcr test, especially if it is plasma that is tested rather han whole blood. This is because the virus can be "hiding" in places like the brain (herpes viruses tend to attack nerve cells) while not much of the virus is in he blood stream. So for hhv6 an antibody test is probably a better indication of infection. If you want a pcr, make sure they are testing whole blood. Not always easy. My doc ordered a whole blood pcr to test for cihhv6, but they tested plasma anyway, so it was a waste of time. If this is the case for hhv6 it is probably true for other herpes viruses as well.

 

[PhoenixBurger]

If PCR's were totally unreliable then they should not be offered. My understanding is that PCR's are significantly more accurate than any antibody test. There are very few exceptions to this.

I don't believe one can have a systemic infection that your body is mounting a powerful response to, and come up completely negative on a PCR test... repeatedly... for multiple pathogens showing as acute ... multiple times ... over a period of a year.

That's just too many "also's" in one sentence for me. In such a case I would tend to err on the side of immune disorder, rather than PCR error. No?

The Infectious Disease specialist took one look at my negative Lyme PCR and sent me home. And he was holding in his hands two separate positive antibody tests.

 

[Ema]

The Lyme specialists I've worked with often run PCR tests in series for the reasons @vamah laid out. If you are positive for PCR, you definitely have it but a negative result cannot rule it out.

My friend had a series of 5 PCRs done to confirm Lyme...along with a positive antibody test. Eventually she did get a positive PCR (actually 3) but it is just much more common unfortunately to get a false negative.

 

[Sushi]

The Lyme specialists I've worked with often run PCR tests in series for the reasons @vamah laid out. If you are positive for PCR, you definitely have it but a negative result cannot rule it out.

My friend had a series of 5 PCRs done to confirm Lyme...along with a positive antibody test. Eventually she did get a positive PCR (actually 3) but it is just much more common unfortunately to get a false negative.

@PhoenixBurger

I had negative antibody tests and positive PCR. They have amplified PCR now which, I assume is better, but it is hard to "catch" some of these pathogens in the blood as they hide out in different places. With Lyme and co-infections, you are more likely to get a positive PCR after antibiotics which stir them to life (scientific, I know! ) They are intracellular infections so are not found easily in the blood.

Sushi

 

[SOC]

I don't believe one can have a systemic infection that your body is mounting a powerful response to, and come up completely negative on a PCR test... repeatedly... for multiple pathogens showing as acute ... multiple times ... over a period of a year.

You don't have to believe it, but it is scientific fact. You can have a serious infection that is causing a powerful immune response and doesn't show up on your current pathogen tests. For one thing, we don't have tests for every pathogen that exists on earth. Also you are unlikely to be given every single pathogen test that does exist. So an unusual pathogen could easily be missed by common testing.

PCR test is specific to a particular pathogen. A different, related pathogen, or a variant of the pathogen could come up negative on a specific PCR test. That doesn't mean you don't have a pathogen. Your body might produce antibodies to the related pathogen which cross-react with antibody tests for other pathogens, so you get a positive antibody, negative PCR situation.

None of these tests is 100% accurate. That's simply the nature of testing. Antibody tests don't test for the pathogen directly, they test for the antibodies your body produces in response to a pathogen. There are lots of places such secondary tests can go wrong. Your body might not produce antibodies correctly. The antibody test might be reacting to some antibody which is similar to, but not exactly the same as the antibody to the pathogen under consideration (cross-reactivity). Testing only whole blood or only serum doesn't necessarily find infections from pathogens that are mostly intracellular and not spilling large amounts of foreign material into the bloodstream. There's plenty more ways testing is not 100% accurate. Any honest doctor or lab expert will tell you that.

You might benefit from reading about testing for HHV6 as an example of the weaknesses of blood tests for pathogens. Here is an interesting example about PCR on plasma or serum for HHV6

Yes. HHV-6 is never found in plasma or serum unless there is an active infection (or the individual has ciHHV-6). However, the absence of HHV-6 DNA in the plasma/serum does not mean that there isn’t a low-level persistent infection in the tissues (e.g. heart, thyroid, brain). HHV-6 DNA is not found in the plasma/serum except during the initial infection and transiently during an acute infection.

Some doctors suspect that we might be suffering from an as-yet unknown pathogen -- possibly mostly tissue-based -- that is similar to, but not the same as some currently known infections. That could explain why tests for known pathogens sometimes come up positive (cross-reactivity) and other times not, and why some antivirals and abx are improving patients' health even when the testing isn't clear. This is sheer speculation at this point. This elusive possible pathogen has not been found and may not exist, but the hypothesis could explain some of our unusual test results.

 

[MeSci]

Antibodies can persist for years after infection, when the pathogen is long-gone. The duration of persistence appears to vary according to various factors.

 

[vamah]

If PCR's were totally unreliable then they should not be offered. My understanding is that PCR's are significantly more accurate than any antibody test. There are very few exceptions to this.

I don't believe one can have a systemic infection that your body is mounting a powerful response to, and come up completely negative on a PCR test... repeatedly... for multiple pathogens showing as acute ... multiple times ... over a period of a year.

That's just too many "also's" in one sentence for me. In such a case I would tend to err on the side of immune disorder, rather than PCR error. No?

The Infectious Disease specialist took one look at my negative Lyme PCR and sent me home. And he was holding in his hands two separate positive antibody tests.

I got my information from the HHV6 Foundation web site. They have a lot of good information. Sometimes a pcr is a better test because some people have antibodies left over from previous infection that is now gone and others don't produce antibodies even if they have an infection. But with some, like hhv6, the virus is in such small amounts in the blood that it is virtually undetectable, in which case I would trust an antibody test. Or course, you can have antibodiea but no active infection, so you have to look at your viral antibody levels to see if they are high enough to make an active infection likely.

 

[PhoenixBurger]

You don't have to believe it, but it is scientific fact. You can have a serious infection that is causing a powerful immune response and doesn't show up on your current pathogen tests. For one thing, we don't have tests for every pathogen that exists on earth.

Nowhere in this thread did I state that it might not be a *different* pathogen. I very clearly stated that it can't be *the ones I tested for*.

Why is quoting me accurate here? Because as you already are aware, Dr. Rey wants to put me on Valcyte for CMV. Im not going to take Valcyte (cancer/infertility risk) if I don't even have CMV. Therefore I need to know if these antibody tests are even accurate.

When i see negative PCR's in the setting of medications *known* to cause IRIS, it kinda seems like a huge sign pointing towards the paradoxical form of IRIS.

Secondly,

How likely is it that there is a single, or *several* mystery pathogens that are actually going to trigger false positives on ALL my antibody tests like this? I would say the chances of that are nearly zero. Obviously. So while your theory is "scientific fact", it is not relevant to this discussion. One pathogen can affect an unrelated antibody test. Sure. Its not going to make all these tests come positive at the same time.

But what *can* happen? IRIS can happen.

By very definition Paradoxical Iris is "the mounting of an immune response to multiple past infections that have been previously resolved".

1) Immune response = Positive Antibody Results
2) Past infections = childhood (CMV, EBV, etc) all things I know I had as a child.
3) Previously resolved = Negative PCR (!!)

Common sense would say its far more likely that I am dealing with Immune System dysfunction, than some secret mystery pathogen that has the super power of making Lyme, Coxsackie, EBV, and CMV antibody tests erroneously positive.

---------------------

Also I am not talking about the whole Lyme world where all common sense is thrown right out the window. Absolutely no test is reliable for Lyme, because no matter WHAT your result is, there will be some doctor telling you the result is possibly wrong.

Antibody: Positive twice, acute, current infection.
PCR: Negative twice.
Western Blot: Only 1 band positive out of them all = Negative.
C6 Peptide: (Gold Standard) - Negative.

Conclusion? Same damn thing. Positive antibody, negative everything else - immune system mounting a response to a previously resolved infection.

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If you're interested in knowing. The drug I took - AZT - destroys bone marrow production for a significant period of time. This destroys the immune system. This is how I can get IRIS without having a suppressed immune system prior to taking AZT.

 

[SOC]

@PhoenixBurger
In order to have Immune Reconstitution Inflammatory Syndrome (IRIS), you have to have had immune suppression first. That's where the reconstitution part comes in -- if it's not suppressed, it won't be recovering (reconstituting). You have told me repeatedly that you did not have either an immune suppressing virus or immune suppressing medications. This is likely why no immunologist will believe you have IRIS.

There are two common IRIS scenarios. The first is the “unmasking” of an occult opportunistic infection. The second is the “paradoxical” symptomatic relapse of a prior infection despite microbiologic treatment success. Often in paradoxical IRIS, microbiologic cultures are sterile. In either scenario, there is hypothesized reconstitution of antigen-specific T cell-mediated immunity with activation of the immune system following HIV therapy against persisting antigen, whether present as intact organisms, dead organisms, or debris. [3]

Though these symptoms can be dangerous, they also indicate that the body may now have a better chance to defeat the infection. The best treatment for this condition is unknown. In paradoxical IRIS reactions, the events will usually spontaneously get better with time without any additional therapy. In unmasking IRIS, the most common treatment is to administer antibiotic or antiviral drugs against the infectious organism. In some severe cases anti-inflammatory medications, such as corticosteroids are needed to suppress inflammation until the infection has been eliminated.

http://en.wikipedia.org/wiki/Immune_reconstitution_inflammatory_syndrome

The facts that you did not have immune suppression in the first place and that your reaction is lasting much, much longer than paradoxical IRIS are the likely reason immunologists won't agree with your self-diagnosis of paradoxical IRIS.

Inaccuracy of current virus testing, both antibody titres and PCR, is a reality, and so may be a factor in the ambiguity of your diagnosis. Your doctor is suggesting a possible interpretation and a viable treatment plan. You don't like either. That's fine. It's never good to follow anyone blindly. It sounds to me like you need to seek out another doctor.

 

[MeSci]

In case this is helpful to understanding what antibody tests results can mean, there is info here

In the normal situation, antibodies are produced on exposure to a pathogen or vaccine, to provide immunity to the pathogen next time it is encountered. Antibodies are one of the body's long-term defences against pathogens, so they - or the precursors which have been primed to produce them - persist for years, sometimes decades, once they have been produced.

 

[Little Bluestem]

And despite the fact that this clearly paints a picture of a confused immune system fighting off past infections (Classic IRIS), all physicians agree that it is impossible to experience IRIS without an immune suppressing disease like HIV.

ME, once call Chronic Fatigue Immune Deficiency Syndrome, does not qualify as an immune suppressing disease?

 

[SOC]

ME, once call Chronic Fatigue Immune Deficiency Syndrome, does not qualify as an immune suppressing disease?

I think it does. I had an IRIS or IRIS-like response to Valcyte. And I have immune tests showing immune abnormalities.

PhoenixBurger is claiming his "IRIS" started when he was perfectly healthy -- before ME/CFS or any other immune dysfunction.