Maintaining IgM Antibodies for Years, Poor Prognosis in LD

Medical topics with questions, information and discussion related to Lyme disease and other tick-borne diseases.
Henry
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by Henry » Wed 28 Dec 2011 14:36

ChuckG: The mathematical equation for the dissociation constant indicates that valency is an exponential function. In this case, a difference of 3 equates to 10 to the third power or 1,000. But, that is an approximation. The important thing to remember that this enhances the opportunity to detect binding to minor antigenic determinants that would not be detected by IgG antibodies thereby resulting in false positives. Please keep in mind that protein bands (e.g., 31 and 34 kDa) contain MANY potential binding sites for antibodies, not just one that is specific for 31 and 34 kDa. IgM antibodies might detect some of the very minor binding sites that are irrelevant to diagnosis for Lyme disease. That's just the nature of the beast.

ChuckG
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by ChuckG » Thu 29 Dec 2011 2:55

Henry

Thanks.

Claudia
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by Claudia » Fri 2 Mar 2012 15:47

From Relative Risk Blog, March 1, 2012
http://relative-risk.blogspot.com/2012/ ... or-ld.html

IgM Blots for LD

Some notes on:
High frequency of false positive IgM immunoblots for Borrelia burgdorferi in Clinical Practice.
V. Seriburi, N. Ndukwe, Z. Chang, M. E. Cox and G. P. Wormser. Clin. Microbiol. Infect. March 2012.

According to those guidelines from the Centers for Disease Control and Prevention (CDC), which remain in current usage, seropositivity requires a reactive first-tier test, usually an enzyme-linked immunosorbent assay (ELISA), plus either a positive IgM or a positive IgG immunoblot. If a patient’s symptoms have exceeded 4 weeks, the IgG immunoblot in particular must be positive. Immunoblots are not considered positive unless the reactive bands present are those that satisfy the recommended evidence-based criteria for positivity.

Although the specificity of two-tier serologic testing has exceeded 99% in research studies when the testing was performed by highly proficient reference laboratories, in actual clinical practice two-tier testing has performed less well, presumably due to over-reading of weak bands on the IgM immunoblot. Despite recognition of this problem by many health care providers in clinical practice, it has never been systematically studied in this setting. Because false positive Lyme IgM immunoblots may lead to misdiagnosis, unnecessary antibiotic therapy with possible adverse effects, and thereby unnecessary expenditures, we attempted to examine this phenomenon in the clinical practice of one of the coauthors of this report.

A total of 249 patients were seen over the 34 month study period, of which the medical records of 248 patients were available for review. 182 patients (73.4%) were referred for evaluation of possible Lyme disease. 94 patients had a positive IgM immunoblot for antibodies to B. burgdorferi, of whom 50 (53.2%) were deemed to be false positive….

Of the 50 patients found to have a false positive IgM immunoblot, 47 of the 50 (94.0%) failed to meet CDC criteria for seropositivity: 45 patients (90.0%) had symptoms in excess of 4 weeks at time of testing, 39 (86.7%) of whom had symptoms in excess of 8 weeks; 11 (22.0%) had a negative first-tier serologic test; 20 (40.0%) did not have a first tier test done; and for 6 (12.0%) the bands required to meet CDC criteria for a positive IgM immunoblot were not present despite an interpretation of seropositivity by the laboratory performing the testing. Overall, 32 patients (64.0%) had negative or no concomitant first-tier testing and/or the band pattern did not meet CDC criteria.

False positive IgM immunoblots were not restricted to any one particular commercial laboratory. However, two commercial laboratories widely used in the Northeastern United States accounted for 50% of the false positive results, although only what have been referred to ‘Lyme speciality laboratories’ used interpretative criteria different from what has been recommended by the CDC.

Overall, of the 94 patients referred for possible Lyme disease by another physician, 23 (24.5%) had a false positive IgM immunoblot compared with 27 (30.7%) of the 88 self-referred patients, p 0.41. At least 39 (78.0%) of the 50 patients with a false positive IgM immunoblot had received antibiotic therapy because of this finding. Indeed, 14 (28%) had received multiple courses of antibiotic therapy. One patient had received 6 months of antibiotic therapy and 4 (10.3%) of the 39 patients who were treated had even received a course of intravenous antibiotic treatment.

There are several limitations to this study. For example, the results do not provide any information on the actual specificity of the IgM immunoblots when performed by commercial laboratories, only that such findings are commonly encountered among patients referred for possible Lyme disease to a private practice of an Infectious Diseases physician in a Lyme disease-endemic area. In addition, the practice of this particular Infectious Diseases physician, who has had a special interest in Lyme disease, may not be representative of other Infectious Diseases practitioners in Lyme disease-endemic areas or in non-endemic areas, or for those who care for pediatric patients.

In any case, it is quite clear that some clinicians are not following the CDC recommendations in place since 1995 for ordering conditional Lyme disease serologic testing, in so far as immuno-blot testing is being requested independently of whether a first-tier test is reactive or even done. It is also clear that some clinicians are either not aware of, or not following, the recommend-ations for interpretation of serologic test results, because patients with chronic non-specific symptoms are being diagnosed and treated for Lyme disease based solely on a positive IgM immunoblot test result. The false positive IgM immunoblot results observed in this study were probably related to over-reading of weak bands for the most part, as has been suggested by others.

Research on alternative testing strategies that eliminate the IgM immunoblot entirely is ongoing. One approach that has shown promise is the substitution of the C6 ELISA serologic test for the immunoblots as the second-tier test. The C6 ELISA is a commercially available assay that is highly sensitive for early Lyme disease and yet is usually indicative of the presence of IgG rather than IgM antibodies to B. burgdorferi. Additional research on this topic is warranted.

awmurawski
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by awmurawski » Tue 20 Mar 2012 2:44

The article is a crystal-clear example of result-driven, speculation-based drivel.

Justifying the speculative conclusions of this article by discussing IgM vs IgG antibodies in general is nonsensical. In the case of B. burgdorferi, the combination of IgM antibodies 31 and 34 is 100% specific as proven by PCR analysis -- even if band 31 and 34 alone are cross-reactive. The reappearance of IgM antibodies is likely to due to well-documented antigenic variation (epitope switching) in B. burgdoferferi infection.

--Anthony Murawski
Seattle, WA

awmurawski
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by awmurawski » Tue 20 Mar 2012 8:22

"Because I am not an MD", means because I am not qualified, competent to do what you suggest. I lack the training and EXPERIENCE. And I realize that just because I have a modem and understand how to type a word into a search engine, that doesn't qualify me to have an opinion on the matter that counts and I think that we need to respect the abilitites of professionals within the boundaries of their profession. Yes, we are all entitled to our opinions. But we want those with the experience and understanding to do the analysis."

No, we don't have to respect the abilities of professionals within the boundaries of their profession." That's absurd. I've met only one doctor -- including multiple neurologists and infectious disease doctors -- who could comprehend my research on Lyme disease, although I have no medical training. Most of us are capable of educating ourselves quite thoroughly, and the majority of clinicians I've encountered are borderline incompetent, because they are 5-10 years behind the research. Incidentally, if you'd like to see my research and hypothesis on kynurenine pathway-mediated excitotoxicity and immune system dysregulation in Lyme disease, and the contributory role of herxing in immune system dysregulation, go to https://www.yousendit.com/transfer.php? ... YURMYnNUQw

We have to learn to stop respecting the opinions and abilities of professionals merely because they have a degree and plenty of experience misdiagnosing people (in the case of IDSA docs).

Anthony

Most ofcapable of understanding

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Spanky
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by Spanky » Tue 20 Mar 2012 15:15

"awmurawski":
I've met only one doctor -- including multiple neurologists and infectious disease doctors -- who could comprehend my research on Lyme disease, although I have no medical training.
That's not terribly surprising.

awmurawski
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by awmurawski » Tue 20 Mar 2012 16:21

Oops, provided the wrong link for my draft article. Here's the correct link:
https://www.yousendit.com/transfer.php? ... NEs5TE5Vag

Anthony

awmurawski
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by awmurawski » Tue 20 Mar 2012 19:28

I wrote, "I've met only one doctor -- including multiple neurologists and infectious disease doctors -- who could comprehend my research on Lyme disease, although I have no medical training." I'm talking about personal consultations. Incidentally, that one doctor was a psychiatrist who has little familiarity with Lyme disease. Among LLMDs, I email with a couple of docs who understand the research, e.g., Bob Bransfield.

In a previous message on this topic, someone wrote that he/she was far more ill after antimicrobial therapy than prior to treatment. I had the same experience. My article provides what I believe is a strong hypothesis as to why that would be the case for someone who has been infected for quite some time, with severe symptoms.

I think there's a special place in hell for the IDSA Lyme docs, but I'd also say the vast majority of LLMDs don't know what they're doing when dealing with long-standing, late-stage Lyme/coinfectons.

--Anthony

Claudia
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by Claudia » Mon 16 Apr 2012 14:19

In searching and reviewing some information on this board about immune response recently I came across this statement about maintaining IgM antibodies and patient outcome by Tom Grier that mirrors information in my first two posts on this thread; one from the American Nurses Association, and another from a medical text book on Infectious Disease, series editor is from the National Institute of Allergy and Infectious Disease, National Institute of Health (http://www.lymeneteurope.org/forum/view ... f=6&t=3345). As I've mentioned earlier in this thread, this antibody pattern and chronic illness has also been noted in the majority of the Lyme disease patients seen by my son's neurologist:
Laboratory Tests
By Tom Grier

Immune Responses

The IgM antibody will only stay in circulation for about six months, and then levels are usually too low to detect. If infection persists, this antibody may also persist. In general, a Lyme patient who consistently has detectable IgM levels is usually chronically ill, but its absence is not a reliable indicator of cure.

http://www.lymeneteurope.org/info/laboratory-tests

Camp Other
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Re: Maintaining IgM Antibodies for Years, Poor Prognosis in

Post by Camp Other » Mon 16 Apr 2012 17:05

Claudia,

I've been working on more research on this topic and came across the same resources you have. I'm trying to tie in any research I can find in general about antibody response - including an undulatory immune response - to make sense of the variations if there is sense to be made.

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