Sunday, February 14, 2010
The IgM question: Is it chronic Lyme disease?
The Lyme debate is not unusual in medicine, or so I say. To other
physicians I claim that it is not unusual for doctors to disagree. This
makes it more palatable. In truth: I cannot think of another disease
that has elicited
so much vitriol, controversy and ugly politics. This blog is for new
patients; perhaps many others will benefit from what follows. Visits are
brief--I try to accommodate
many patients. Patient stories are long. By necessity, I have to boil
them down to their essence. Many themes are repeated over and over
again--as are many questions. My next series of entries are attempts to
answer questions which are not as simple as one might think.
Many patients have been told they do not have chronic Lyme disease because Western blot antibodies are in the IgM class, not the IgG class. Normally, the immune system makes IgM antibodies in early infection and then makes IgG antibodies in late infection. Patient selection for major clinical studies have been chosen based on IgG responses. Mainstream thinking claims that the lack of Lyme IgM antibodies into IgG antibodies is evidence the test is false positive. At any rate, this excludes the diagnosis of chronic Lyme disease. All major NIH sponsored studies have only included patients who are CDC positive by IgG standards. In addition, the CDC allows for skipping the 2 stage test (an improvement? I think not): ELISA then Western, if the patient sample is IgG positive. I have recently scoured the medical literature in search of papers which address the Lyme IgM/IgG issue. There are hundreds of scientific paper published about Lyme disease--many recent. The IgM vs IgG issue remains largely untouched.
What I have found is that: Steere published an ancient studyof Lyme patients infected 20 years ago. He found persistent antibodies of both the IgM and IgG class. Igenex has clinical studies: the presence of 2 specific IgM (or IgG) bands shows exposure to Borrelia burgdoreri (Lyme). There are studies which discuss false positive reaction as well as studies which discuss the specificity of certain antibodies. Existing literature supports the idea that certain Western Blot antibodies are highly specific for Lyme. Heuristic reasoning would lead one to a conclusion opposite that posited by mainstream medicine. As stated, IgM antibodies are seen in early and therefore acute infection with Lyme organisms. The persistence of IgM antibodies would suggest the immune system is "chronically" seeing Borrelia as an acute--new infection. IgG antibodies, seen in late infections with other organisms, are frequently used as a measure of immunity. Studies which select chronic Lyme patients with IgG responses may be inherently biased--ommiting the most common patient type. Patient selection for studies has been difficult because of patient recruitment limitations.
Why IgM? There are no studies which acknowledge this anomaly, let alone have studied it. I can postulate. IgM and IgG antibodies are produced by the same cells: B lymphocytes. These lymphocytes may become plasma cells. The switching from IgM to IgG antibodies occurs by amolecular switching. This class switching--IgM to IgG-- frequently fails to occur. Is it because Borrelia hide from the immune system--change the reactive antigens? I don't know. Normally af IgG antibodies are used as a metric for immunity from a particular germ. Memory cells persist. These memory cells produce IgG antibodies which block re-infection. Perhaps memory cells are not produced in chronic infection with Borrelia burgdorferi infection. The question remain unanswered.
What do we know: Lyme is associated with more IgM than IgG antibodies. Certain antibodies, for example: 18, 23, 31, 34, 39 41?, 93 are HIGHLY specific for exposure to Lyme bacteria.
The argument that chronic Lyme can only be diagnosed when 5/10 IgG, CDC surveillance bands are present--which exclude 31 and 34, makes no logical sense. The exclusion of 2 very specific antibodies relates to a failed vaccine. The 10 antibodies were part of an epidemiological tool devised in 1994. This tool was never intended for diagnosis, but has morphed into a diagnostic criteria used by infectious disease physicians for the inclusion/exclusion of Lyme infection. Recently a patient with 7/10 of these antibodies was sent for a C6 peptide test for confirmation, because the infectious disease physician thought these reactions might be a false positive. Side bar: the C6 test measures reactivity to a protein, ViSE. The ability of this particular antigen to mutate is well established; the utility of this test has lessened over time.
A recent patient (last week) told me the previous doctor told her she could not have chronic Lyme because a positive two-tier Western blot showed only IgM antibodies. I was asked to refute this during part of a 30 minute office visit.
Infectious disease physicians read from a script wthout critical analysis (my opinon).
The next series of blog entries will discus questions related to Lyme controversies. All of these entries are my opinions. Readers should be aware that my opinions more often than not, differ from those of mainstream sources including: IDSA, CDC and many experts and clinical investigators.
Many patients have been told they do not have chronic Lyme disease because Western blot antibodies are in the IgM class, not the IgG class. Normally, the immune system makes IgM antibodies in early infection and then makes IgG antibodies in late infection. Patient selection for major clinical studies have been chosen based on IgG responses. Mainstream thinking claims that the lack of Lyme IgM antibodies into IgG antibodies is evidence the test is false positive. At any rate, this excludes the diagnosis of chronic Lyme disease. All major NIH sponsored studies have only included patients who are CDC positive by IgG standards. In addition, the CDC allows for skipping the 2 stage test (an improvement? I think not): ELISA then Western, if the patient sample is IgG positive. I have recently scoured the medical literature in search of papers which address the Lyme IgM/IgG issue. There are hundreds of scientific paper published about Lyme disease--many recent. The IgM vs IgG issue remains largely untouched.
What I have found is that: Steere published an ancient studyof Lyme patients infected 20 years ago. He found persistent antibodies of both the IgM and IgG class. Igenex has clinical studies: the presence of 2 specific IgM (or IgG) bands shows exposure to Borrelia burgdoreri (Lyme). There are studies which discuss false positive reaction as well as studies which discuss the specificity of certain antibodies. Existing literature supports the idea that certain Western Blot antibodies are highly specific for Lyme. Heuristic reasoning would lead one to a conclusion opposite that posited by mainstream medicine. As stated, IgM antibodies are seen in early and therefore acute infection with Lyme organisms. The persistence of IgM antibodies would suggest the immune system is "chronically" seeing Borrelia as an acute--new infection. IgG antibodies, seen in late infections with other organisms, are frequently used as a measure of immunity. Studies which select chronic Lyme patients with IgG responses may be inherently biased--ommiting the most common patient type. Patient selection for studies has been difficult because of patient recruitment limitations.
Why IgM? There are no studies which acknowledge this anomaly, let alone have studied it. I can postulate. IgM and IgG antibodies are produced by the same cells: B lymphocytes. These lymphocytes may become plasma cells. The switching from IgM to IgG antibodies occurs by amolecular switching. This class switching--IgM to IgG-- frequently fails to occur. Is it because Borrelia hide from the immune system--change the reactive antigens? I don't know. Normally af IgG antibodies are used as a metric for immunity from a particular germ. Memory cells persist. These memory cells produce IgG antibodies which block re-infection. Perhaps memory cells are not produced in chronic infection with Borrelia burgdorferi infection. The question remain unanswered.
What do we know: Lyme is associated with more IgM than IgG antibodies. Certain antibodies, for example: 18, 23, 31, 34, 39 41?, 93 are HIGHLY specific for exposure to Lyme bacteria.
The argument that chronic Lyme can only be diagnosed when 5/10 IgG, CDC surveillance bands are present--which exclude 31 and 34, makes no logical sense. The exclusion of 2 very specific antibodies relates to a failed vaccine. The 10 antibodies were part of an epidemiological tool devised in 1994. This tool was never intended for diagnosis, but has morphed into a diagnostic criteria used by infectious disease physicians for the inclusion/exclusion of Lyme infection. Recently a patient with 7/10 of these antibodies was sent for a C6 peptide test for confirmation, because the infectious disease physician thought these reactions might be a false positive. Side bar: the C6 test measures reactivity to a protein, ViSE. The ability of this particular antigen to mutate is well established; the utility of this test has lessened over time.
A recent patient (last week) told me the previous doctor told her she could not have chronic Lyme because a positive two-tier Western blot showed only IgM antibodies. I was asked to refute this during part of a 30 minute office visit.
Infectious disease physicians read from a script wthout critical analysis (my opinon).
The next series of blog entries will discus questions related to Lyme controversies. All of these entries are my opinions. Readers should be aware that my opinions more often than not, differ from those of mainstream sources including: IDSA, CDC and many experts and clinical investigators.
Posted by
Lyme report: Montgomery County, MD
at
7:19 AM
