I have been blogging since 2008. To date the most popular page views is “The IgM question, is it chronic Lyme.” Updated post 12/27/17 with additional information. I re-read my entry, 1/15/18. The post has been updated. A study by Aucott, JHH shows that a subset of patient, those destined for chronic illness, make a poor IgM response to infection and incapable of IgG class switching. This is discussed elsewhere.
Many patients I see have been told by their physicians that the
IgM results on a Western Blot test indicate only recent infection; and many of these patients have been told that their
positive Lyme test was a false positive when the expected IgG bands did not
This is not surprising. This conclusion corresponds with
statements made by the IDSA and CDC.
These groups (CDC/IDSA) admit recommended test lack sensitivity in early
Lyme disease but claim their two-tier test is 99% accurate in late disease, at
which time the requisite 5/10 IgG antibody bands will reliably appear.
In the usual course of events when our bodies are exposed to pathological infectious agents oour immune system first makes IgM antibodies; but after a period of days or weeks the relatively ineffective IgM antibodies are supplanted by the more effective IgG antibodies. But as I frequently explain to my patients: Lyme does not play by these rules.
There is much that controversial about this disease and some
of the controversies are legitimate. The IDSA/CDC statements about antibody responses
associated with Lyme disease are completely false and should be expunged from the controversy. The
immunological responses seen in Lyme disease, in all stages of the disease show a predominant IgM
antibody response and a poor IgG response in the majority of cases. Of course there are exceptions to this rule. In general,
overall production of antibodies of either class in response to infection may
be quite poor.
Why this occurs I do not know. The immune system is
incredibly complex and scientist are learning more about it every day. There is
an interplay between invading germs and immune responses. These relationships
are different with every single pathogenic germ. With Lyme disease, it has been
widely reported that infection causes down-regulation of cytokines and
inactivation of complement fixation as a mechanism for survival.
Both IgM and IgG antibodies are made by the same B
lymphocytes and plasma cells. These cells which manufacture antibodies receive
signals from specialized proteins and cytokines which leads to change in
DNA transcription and the manufacture of the new class of antibodies. This is referred
to as class switching. Defects in this switching mechanism have been described
in both genetic and acquired diseases. It is not difficult to imagine that
infection with Lyme somehow influences this switching mechanism so that IgM antibodies
are favored. If this is correct, it may underlie a novel mechanism of immunosuppression.
Of course many practitioners see Lyme disease, chronic infection with Borrelia burgdorferi
species and strains, as an immune suppressed state in the host or patient.
I am looking at a patient laboratory report from Stony Brook University
Medical Ctr., Lyme Disease laboratory, Western blot results are: IgM bands, 18,
23, 25, 31, 41, 64 and 93. The IgG Western Blot strips to appear identical to
the control. No bands are identified.
If I was of the IDSA ilk I might conclude this test shows serological
evidence of acute Lyme infection only. I would have a hard time explaining the
31 band. The 31 band represents a reaction with outer surface protein A (OspA).
This particular antigen is expressed in the gut of the Ixodes tick, disappears
in the salivary glands before the spirochetes are injected into the host and does not reappear in the host for at least six
months. If I was of the IDSA persuasion I would have to call the 31 band a
false positive. Otherwise the results would make no sense. There are two problems with
this resolution. First, this reaction is highly specific -- this protein is found
only on the surface of Borrelia burgdorferi thus false positives would be unexpected; and -- second, these results are from
one of the country’s top Lyme disease laboratories whose credentials are
unimpeachable. But luckily I am not of the IDSA persuasion. Because I know that
only IgM antibodies or a predominance of IgM antibodies are frequently seen in patients with chronic Lyme disease.
This patient has been sick with Lyme disease since 1988 at
which time she presented with Bell’s palsy and acute meningitis. These lab
results are from two weeks ago. She has been treated for chronic Lyme disease
by several physicians for more than two decades with a variety of intravenous
and oral antibiotics. She has many unresolved chronic symptoms but is able to
function reasonably well. She becomes disabled with severe relapses whenever
antibiotics have been discontinued. The use of long-term antibody therapy
allows for some reasonable quality of life. Without access to antibiotics her
quality of life would be zilch.
The answer to the question: can IgM antibodies alone are
seen in chronic Lyme is clearly yes.
It is frequently argued by the IDSA that Lyme disease must
act in a particular way or test in a particular way because there are no
precedents in nature to backup contentions to the contrary. This thesis is specious.
According to the CDC, tuberculosis is one of the deadliest
diseases and infects one third of the world’s population. An awful lot of
research is been done over many years looking for antibody test to help physicians
diagnose this infection. To date, none has been found. ( lymphocyte transformation test available -- imperfect test) 90% of patients infected with tuberculosis produce
antibodies. The specific antibodies produced vary from patient to patient in
ways that are impossible to predict. After decades of research there is no
antibody test for tuberculosis with a sensitivity greater than 20%.
Tuberculosis which is usually localized to the lungs,
requires treatment with several antimicrobials for numerous months and relapses
According to the CDC, patients with Q fever causing cardiac
involvement need treatment with two antibiotics for at least six months.
According to the CDC advanced cases of brucellosis may
require treatment for six months with dual antibiotic therapy.
Many infectious diseases are entirely unique and without
precedents in nature.
Lyme disease is different from other infectious diseases in
numerous ways. One of those ways is that infection tends to be associated with
production of IgM antibodies and not IgG antibodies. An investigation into this
anomaly should be fertile ground for future research.
Older studies, Steere et. al, show that IgM antibodies may be present many years after acute infection with Lyme.