Rules for interpreting the significance of IgM and IgG antibody titers

I am trying to find some authoritative sources on the general rules for interpreting the significance of IgM and IgG antibody titers in the context of viral and microbial infections.

On slide 5 of this presentation, those rules are given as follows:

The above is also my own understanding of how IgM and IgG titers are interpreted.

However, I cannot find any other source on the Internet (authoritative or otherwise) detailing these general rules, which seems strange.

Would anyone have a link to an authoritative source which details the rules of IgM and IgG titer interpretations?

 

Hi @Hip All I know is that most labs in Norway have these rules on their webpages along with values and ranges for all the tests they offer.

ETA:

 

I think those rules are just based on an extrapolation from what is known about the rates of Ig class production following encounter with antigen - from the 1950s. They ought to be generally true but in fact in all sorts of situations they probably aren't. Titres are really only any use when studied in pairs - to show change. As a physician I would not base a clinical decision on one set of readings. High IgG is pretty strong evidence of infection at some time, but that's about it.

The EBV literature is full of discussions about how unreliable these sorts of rules are in individual cases.

 

Hi @Hip,

When I was asking about IgG in another thread, @Aroa foind this for me in Naviaux’s work (https://www.omf.ngo/2016/09/09/upda...-fatigue-syndrome-q-a-with-robert-naviaux-md/, question 11):

I’m interested in IgG because my daughter’s tetanus toxoid IgG increases with histamine exposure (lice, mosquitoes, etc.). This is also the cause of her symptoms. Although I have the data on the IgG rise I don’t have the corresponding NK results, so can’t cross-check to see if this is relevant. Though I hope they are released to me some day.

Hope this helps.

L

 

We have learned in our autism studies with Dr. Judy Van de Water that supertiters of antibodies do not mean new or reactivated viral replication. Supertiters of IgG antibodies mean that the balancing T-cell and NK cell mediated immune activity is decreased.

That looks like fairy tales to me. Antibody production is intimately correlated with T cell help and NK cells make use of antibody to kill (ADCC). Otherwise they have no specificity. And I am not aware of anybody knowing anything useful about immune responses in autism.

Comments like this just make me think how much pseudoscience is passing for professional science these days.

 

@Hip, you may want to check out a reputable Lyme site. They pretty much all have references for explaining IgM/IgG. You could try LymeNet Europe - it doesn't have much traffic these days, but it is study and reference rich.

Your table seems fair enough. One observation is that interpreting a tandem of high IgG with a low IgM as inactive or cured can be misleading on a very basic level. What I mean is if you get infected with, say, Lyme, and you do not treat, and your body is unable to resolve the infection on its own, then after 30 days or so the natural immune response will typically convert from IgM to IgG, if everything is working as it should. You have progressed to Late Stage Lyme. You test it at that point, you should be IgG positive/IgM negative, at least according to conventional Lyme theory. Test it six months later and you still should be IgG positive assuming you have not been treated and your body cannot mount a sufficient immune response on its own. Ditto for 12 months and two years and five years...

But in this scenario, most GP's, in fact, most IDs will assume - sometimes wrongly - that those IgGs' represent an old resolved infection; however, they could instead signify active and unresolved infection. The implications could be profound for the patient

Maybe that's where @Jonathan Edwards insight about measuring at least two points of Ig response come in, ie, pairs over time. Are your values declining over time? Rising? What happens when you treat? Do your values rise? If so, I think there is a general consensus that that would suggest an active infection. This is what happens usually with me relative to Lyme.

Incidentally, having both high IgM and IgG - and this suggesting reactivated disease - happened to me just recently as I tested high on both for Babesiosis. When I first tested positive for Babesiosis at the NIH, I spoke with arguably the world's leading expert on that parasite; he volunteered that once you have it, despite treatment, you may have it for the rest of your life, and I could expect to suffer from reactivation of symptoms, and, perhaps more to the point, see it reflected in my lab results as well. Apparently he was right.

The fun stuff is trying to interpret accurately contradictory titre trends, like going from IgG to IgM. Everybody up on their antigenic variation theory?

 

Yes, the interesting thing is that antibody titer interpretation is performed differently by ME/CFS and Lyme specialists compared to regular infectious disease (ID) specialists.


At the moment I am gathering info in order to write a new thread on the problems of antibody titer interpretation in ME/CFS.

The rules of thumb detailed in the first post are the ones that regular infectious disease specialists and the medical profession as a whole use as guidelines to diagnose infection.

You can see from those rules that in general, ID specialists only diagnose an active infection in cases when IgM is high.

High IgM suggests a "proper" active infection as we normally understand them — an infection that is either an initial acute infection, or a flare up and reactivation of an old infection. Such "proper" infections with high IgM typically also show up positive if you test the blood for the presence of the virus by PCR.


In the case of ME/CFS and Lyme, however, IgM is usually low, but IgG titers are chronically high.

To an ID specialist, that finding of low IgM but chronically high IgG is curious, but they do not see it as an active infection (especially as blood PCR tests are usually negative in ME/CFS — you don't see much virus in the blood in ME/CFS).

But to an ME/CFS specialist doctor, low IgM with chronically high IgG signifies there may be some sort of infection going on in the tissues. (Of course this is controversial, as others believe the high IgG in ME/CFS is of no significance, and don't believe ME/CFS is caused by ongoing infection).

 

Thank you, that's what I was hoping to confirm, that these rules are thought to be generally true (even though there may be various exceptions here and there).

 

Yes. I must confess that sometimes I am taken aback at how provincial GPs and infectious disease doctors can be. And how arrogant and demeaning in their casual ignorance.

 

For my purposes, I am not so much interested in this controversy here; just focusing on the practical issues of viral testing in ME/CFS. For my purposes I am assuming that the ME/CFS specialists' interpretation is valid.


But this still leaves us with a difficult practical issue: what exactly do we mean by high IgG titers? How do we know if the IgG titers on our viral test reports are high or not? The lab report provides no information about whether your IgG titers are high or not. (The only reference range provided on lab reports relates to whether IgG antibodies are absent or present).

This means that ME/CFS patients who get viral testing done themselves (because they cannot get access to a good ME/CFS doctor) are not able to interpret from their lab test results whether they have a chronic active infection.

Usually only experienced ME/CFS doctors can interpret your viral antibody lab report. And this is an issue for ME/CFS patients such as those in Europe who cannot get easy access to a good ME/CFS doctor.

This is the issue I am trying to resolve: how can patients know if they have high IgG?

 

I get some values, e.g. EBV IgG numbers. But for Coxsackie viruses its more whether or not my ratio is high, although I am provided that ratio.

Lyme advocates saw the algorithm for diagnosing Bb evolve and embraced in real time; it was not difficult to uncover its flaws. Of course, communicating that has proven much more difficult.

My point is a possible suggestion is look to the history of the various tests. Depending on where you are, and which labs you can access, values can be generated - I have some of my viral numbers - but you may find a need to appreciate the underpinning logic that went into constructing each metric, in my unqualified opinion. So, if I am right, that might help clarify what IgG values truly constitute high, as opposed to the constructs used (frequently) blindly today.

Not an easy task.

 

Yes, that's roughly the method ME/CFS specialist doctors use to calibrate the viral tests they employ, and to determine what constitutes a high IgG.

ME/CFS doctors will send off a load of blood samples from completely healthy people to the lab, to determine the average IgG viral titer of healthy people. That's what Prof Montoya and Dr Chia did at least.

Then once you know the healthy average IgG for a given lab test, ME/CFS doctors usually define high IgG titers as those which are at least 4 times that average.

So 4 times the average IgG titer of the healthy is the threshold titer that ME/CFS doctors typically use to diagnose a possible chronic active infection.

(Note that when an ME/CFS doctor calibrates a viral antibody test to work out this threshold titer, that calibration is only valid for that particular lab test; the calculated threshold titer will not apply to a test from a different lab; it is lab-specific).


But the issue is that these threshold IgG titers are usually only known to the ME/CFS specialists; it's usually not information that is generally available (except in the case of Dr Chia, who has publicized the threshold titers he uses for chronic active enterovirus infection; but for herpesviruses I could find no publicly available info).

Which means that ME/CFS patients looking at their viral lab test results cannot know whether or not they have a chronic active infection.





(Note that this 4 times average healthy IgG rule used by ME/CFS doctors is not the same as a rule used by regular ID specialists to confirm an acute infection, which is done by looking out for a fourfold rise in IgG titers between acute and convalescent blood samples).