Wednesday, April 9, 2014

The IgM question, is it chronic Lyme? Revisited.

I have been blogging since 2008. To date the most popular page views is “The IgM question, is it chronic Lyme.” I last wrote about this in 2009.

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 appear.

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.  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 may occur.

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.


Joanne Drayson said...

The Resolution of Relapsing Fever Borrelia requires an IgM response
For those of us with IgM deficiency which Horowitz says he often finds in Lyme patients, if Bb is similar and we clearly haven't done the research yet, then that could be another reason why some patients struggle to resolve Lyme

lymie said...

I was under the impression that the IgM reappeared in late lyme because of the antigen shifting and/or reappearance in the blood stream after hiding out in tissues. Or perhaps a case could be made for alternate forms such as cysts and blebs reverting to spirochete form. Wondering if anyone knows how the immune system responds to cysts and blebs.

WLP Romania said...

IgM can be reactivated in chronic lyme, when IgM is positive, it doesn’t mean necessarily recent infection.

Karen Barrett said...

I had an initial test for Lyme...I am very ill with classic symptoms...and NO ONE will prescribe antibiotics for me, despite living in an endemic area, and living in the country and walking the dogs DAILY in my field. I left a doctor today in tears, as I questioned the CDC guidelines and the accuracy of tests. She said, unequivocally, negative serology = NO TREATMENT.

Skippy Lamb said...

I'm a strategic thinker. The first step is to develop very good antigen tests. Once we can confirm the infection is present (whatever type) we can rally enough support to develop a cure and test the effectiveness of that cure. We can call for a "manhattan project".

Without a reliable antigen test it is impossible to know what we are fighting or to get enough resources or a viable way to develop a cure. Thus, the primary goal must be to develop extremely good antigen tests for many pathogens. Developing other extremely good direct methods of testing are acceptable, anything that is highly sensitive, accurate and direct, not antibodies.

MrApplewine said...

The solution is to forget antibodies for diagnosis and stick to antigen and DNA test. The CDC should immediately check the validity of George Mason University's antigen test and Sin Hang Lee pathologist at Milford's whole genome Borrelia test. Stop saying xyz isn't validated and evaluate the validity of non-antibody tests and maybe we will learn something.

Leslie Lim said...

I read your blog.I thought it was great.. Hope you have a great day. God bless.