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Friday, December 4, 2015

Lyme with IgM Western Blot bands only: can it be chronic Lyme? (revisited)

Warning: Even though I tried to simplify this piece I find it is quite complex. Read it slowly.

I have written hundreds of entries in this blog over many years. Consistently, the most popular entry (2010) is: "I have Lyme IgM antibodies only, could I have chronic Lyme?" I am sure readers are consistently hearing from a wide pool of the doctors the answer to this question is no. These doctors are wrong and I will try to explain why in a way I hope my readers will understand.  IgM antibodies are the first antibodies made by "virgin" B cells when a new problem (new germ for example) requires the production of antibodies. This is referred to as a humoral response and is the primary responsibility of the "acquired immune system," contrasted with the innate immune system. Antibody production is a specific learned function of the immune system. IgG antibodies follow IgM antibodies as activated B cells morph into plasma (antibody factories) and the immune response matures. It is reasoned that with persisting infection IgG antibodies will invariably be ramped up as IgM antibodies fade. It is further reasoned that persistent of IgM antibodies in the absence of IgG antibodies is physiologically impossible and therefore such a finding must be a false positive. This line of reasoning is cogent and sensible but is false. My contention is backed up by current science. In a recent, peer reviewed study, A cohort of Lyme patients followed longitudinally was found to manifest only weak IgM responses and no IgG responses. Class switching with transition of B cells to plasma cells failed to occur. This same group of patients was found to have more chronic symptoms.

Link:  W 

Antibodies also called immunoglobulins or Igs. Igs consists of proteins - light chains and heavy chains which form a Y shaped structure. There are various classes of Igs with somewhat different functions: IgA, IgM, IgG, IgD and IgE. IgG has 4 subclasses. There are fixed and variable regions of antibodies. Here I discuss only IgM and IgG. Immunoglobulins are diverse and our immune system can manufacture one hundred million variants - give or take. Variable Ig regions become custom made "keys" which fit into the locks (antigenic determinants) found on Lyme bacteria. These keys (made from light chains) do not change as the antibody class shifts. Constant, variable, heavy chains are swapped out as IgMs transition to IgGs. The portion of the antibody which binds to antigens does not change.  Antigenic determinants are targets on the bacteria which promote the formation of antibodies. These targets, may for example, be outer surface proteins or fragments of flagella - bacterial tails. Bound up antigens and antibodies appear as bands on Western Blot strips at specific sites based on molecular weight of the antigen fragments.

IgM and IgG have different functions - otherwise our bodies wouldn't bother making both types. IgMs are the largest of the antibodies and tend to be produced as pentamers (instead of monomers) the product of 5 IgMs complexed together. IgM antibodies are good at agglutinating masses of germs and activating a cascade of proteins called complement which directly destroys the invading bacteria. Right away there is a problem. Lyme are well known to inactivate complement activity from the get-go. IgM antibodies are active in the blood but are too large to diffuse into the spaces between cells.

IgG antibodies, which are smaller and able to diffuse into the spaces between cells - where Lyme lives - are frequently never produced.

Here is another puzzle piece. Some bands are known to be specific, others less so. Two specific bands (based on antigenic determinants) only appear late during the course of infection. The 31 and 34 bands (outer surface proteins A and B) only appear with infection of greater than 6 month duration.  Yet, in many cases we only find IgM antibodies directed against these two determinants. This is further proof of the concept that chronic, persisting infection may (in the case of Lyme) only elicit IgM antibodies without the appearance of the more active IgG varieties.

Parasites and pathogens evolve mechanisms to evade host defenses and to persist. Here we see that Lyme may allow only the production of weak IgM antibodies, cripple the ability of these antibodies to offer their best fight and completely block the manufacture of Ig G antibodies which would present a more serious threat.

Lyme spirochetes are extremely "smart." From Zhang we learn that antibiotics cannot kill Lyme in a test tube. Peristers are protected in round forms and within biolfim colonies. Here I discuss a mechanism which enhances survivability of the spirochetes in vitro, living systems. Well known research has shown that Lyme are not eradicated in mice, dogs or primates and that the spirochetes persist in humans after treatment.

In summary, not only is it possible for only IgM antibodies to be seen in chronic Lyme but it seems likely that this is the predominant scenario.

Researches like Fallon had an impossible task of finding subjects for clinical trials. The mythical patients with 5/10 CDC IgG antibodies comprised less than 5% of his overall patient population of patients known to suffer with chronic, tertiary neuro-Lyme involving the brain.

Dear reader, if this was all too much to follow the take home message is that most patients with chronic Lyme disease have only IgM bands.

case of Lyme this "normal" immune process appears to more often be the exception rather than the rule.


doglick said...

Hey doc you say that Lyme is rarely detected in the blood. To this I disagree. I've been looking at live blood under the microscope and often find incredible amounts of active spirochetes in infected individuals. Nothing has the motility of these bugs and they are quite visible in my experience.

Ed_Burke said...

You state, "In a recent, peer reviewed study, A cohort of Lyme patients followed longitudinally was found to manifest only weak IgM responses and no IgG responses."

I was unable to find this paper. The link you provide discusses, "Serum Inflammatory Mediators as Markers of Human Lyme Disease Activity". There is nothing about IgM and IgG.

Can you provide a reference to the paper that discusses IgG and IgM response? Thank you.

Lyme report: Montgomery County, MD said...

Look again more carefully. I mention it again today.

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