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.

22 comments:

therileys_13 said...

Excellent blog as usual; keep it up please.
Any thoughts on seronegativity, especially after very prompt use high dose Amoxv? This seems to have totally negated immune response.

Amanda said...

Thank you for your excellent explanation. I have a 16YO daughter who was just diagnosed by her LLMD as having Lyme. Her IgM test came back + from Igenix (even by CDC standards) but IgG was - only having 2 bands. I have been searching the net all weekend trying to find an explanation. The LLMD said the treatment is long and that she'll get sicker before she gets better. Because of the all of the docs who have dismissed us over the past 2 years, I really needed to understand the labs and what they meant to make sure we were on the right course. Thank you I believe we are. Your blog has been very helpful. Seattle Mom!

borrowedsoul said...

I believe the information is out there and the IDSA has it. What it will take for them to treat patients with chronic lyme I just don't know.

Information Services Team said...

Thank you for examining this issue. I too had a positive two strata IgM (WBlot) with a negative ELISA and negative IgG. I have just had a infectious disease consultant from THE top London hospital inform me that I do not have Lyme, ignoring both the WBlot and 9 years of clinical symptoms. Thanks for having the guts to help Lyme patients.

Gina said...

Bravo to you!! Thank you for this informative blog. It is very sad how many people are suffering with Lyme disease without treatment.

My daughter and I both have Lyme disease and we are successfully being treated by a wonderful physician.

Thanks again!!

bricily said...

Not that you need verification of your point, but...I tested IgG positive for all 3 bands in Sept 09 and received the CDC "seal of approval" I also had 2 positive IgM bands. I had been sick for 5 years in cycles and I know for certain that I was bit in 2004.
Is there anywhere a patient can volunteer to be part of research? Where we can say- hey, use my info, sign me up! I want my battle with illness to actually battle and improve knowledge! Thanks for the blog,
Treated in Seattle

CMS said...

I was just diagnosed Weds after two years of chronic fatigue, joint pain, rashes, headaches... and was really thinking something was "up" when the Dr told me that IgM was elevated indicating an early infection. I have had these issues for 2 YEARS, that is not early. What is the prognosis for someone diagnosed 2 years into an infection?

Jill said...

I was just diagnosed had positive Western Blot, IGM positive, but no IGG bands. A traditional doctor told me I do not have cronic lyme because the I have no IGG bands.
I also had the HNK1 CD57 panel result of 27, indicates chronic lyme.

I was bitten about 13 years ago and had multiple bulls eyes rashes, that re-appeared every spring for years. Even with this information the traditional infectious disease doctor does not believe I have chronic lyme. Very frustrating!!

FrenchGirl said...

I've noticed several posts from Seattle. Would love to connect with others who are going through treatment or seeking testing/treatment. Email is French_girl07@live.com. Lynn

Pearl said...

What is the hang up about "chronic Lyme?" Chronic Fatigue Syndrome is defined as having fatigue et.al. for at least 6 months. So if I've had Lyme for at least six months, does that, by definition, mean I have "chronic Lyme?"

I believe I've had Lyme and Bart for 6 years, yet my WB IgM is positive on 18 31, & 41 (positive acc. to IGeneX, negative acc. to CDC), and my WB IgG has only 1 positive band. With over 30 symptoms, I clearly have Lyme. Do I have Lyme or do I have chronic Lyme? Or is "chronic Lyme" only applied to people who resist treatment?

Are doctors looking for an excuse to say, "It's not Lyme"? Why?? Is there some kind of punishment out there for doctors who diagnose Lyme?

LymeMD, Thank you for your rant on "evidence based medicine." Through my recent experience, I have come to the conclusion that most doctors are enslaved to test results, and are uncomfortable and unwilling to make a medical decision without proof. Afraid of being wrong and ridiculed and sued? Perhaps. To me it is proof that they are insecure in their knowledge of Lyme and are unwilling to do the research.

Tt22177 said...

I was have tested positive igm bands 39 and 41 for 8 months now no igg bands. Orginally when i was " diagnosed" by my pcp I was given 3 weeks of anitbotics and went thru feeling like i was dying (vertigo, bells palsy, headches etc). Finally got in to see a ID specialists. Was told it was a false positive test. I shouldve felt better after treatment and all symptoms were " in my head". Now 6 months later still feeling symptoms (fatigue, sore achy muscles,joints, headaches, etc)and pcp is trying to help to best of her ability. Prescribing fibro meds and seeing a chiro. Recently she contacted a ID specialist in Boston who suggested rerun western blot see if igg bands show up. They didnt only igm still. I am at a loss. I know i dont feel well and i know its not in my head. Thanks for posting here makes me feel justified in some way.

Anne P said...

Hi there...a quick question: I've read there are several different bacteria types that are considered lymes. If this is true, would that explain why some people do not get the EM rash? So possible only some of the lymes bacteria actually cause it? And therefore could this also be why it is hard to detect; the tests are only using one bacteria strain vs using all the strains? I hope this made sense...I'm NO doctor, that's for certain.
Thanks,
Anne

kaney said...

Lyme Disease is not a condition that is easy to diagnose. You should already know that it is spread through tick bites (most of the time). You've probably already heard about the rash in the shape of a bulls eye that happens after a tick bite.

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Debbi Milberger said...

By what standard were you confirmed? My 18 year old daughter recently tested positive for lyme with IgM positive. She was treated with 3 Weeks of doxicyclin by our primary doctor while we worked to get her accepted by an infectious disease specialist. We saw him just a few days ago and he immediately stated that the IgM factor indicates a false positive but agreed to test her again. I was initially somewhat relieved but left his office still frustrated because his reasoning was largely based on the fact that we live in Arizona. Another factor is that she also tested positive for herpes simplex IgM but hsv1 & 2 are negative are of great concern to me.

Kristin Hawley said...

My IGM test was negative and my IGG was positive. I have had Lyme twice in the past, and my IGG numbers are higher now than with my last bout of Lyme, so I am being treated again, even though It shows I don't have a current infection because my IGM was negative. Does this seem like chronic Lyme?

Dave said...

I'm sitting in a hospital bed right now for 4 days as they run every test possible on me. I was treated in Aug 08 and Feb 12 for lymes and was giving a 30 cycle of doxy pills. The symptoms came back hard with extreme fatigue, facial paral, ringing in the ears, restless mind, headach, etc. Test just came back 6-10igg and 0-3 IBM neg. Dr says I don't have the lymes and should look towards something else. They ran all test from head to toe and I also found out I have elevated lived enzymes and an enlarged spleen both symptoms of late term lymes...don't know what to do very frustrated.

sabrina said...

Hi there - thank you for this helpful blog. Though, it doesn't totally clear up my confusion! I was hospitalized for an optic neuritis and the only test (or part of test) that came back positive is the serology for IgM. Also, it is positive only for the blood, not for the spinal fluid (if that means anything???). I was released without even any mention of that result so I am assuming they considered it a false positive. Should I be worried and push for a western blot? I lived in NY state so I was certainly exposed to Lyme but I am living in Italy and I am not sure they are so familiar with Lyme...

Marie said...

Hi Sabrina.
They (CDC) wouldn't call your results a "false positive" they would say it is Negative. Like Lyme MD mentioned in his post to be considered positive by CDC criteria you must have at least 2 of the 3 igm and at least 5 of the 10 igg bands to be positive.
I was lucky that I met that criteria for 11 mos. (3 out of 3 and 8 out of 10 for a long time)
I'm now considered negative (by CDC criteria) after a yr. of abx. My "negative" is higher than some fellow Lymies "positive" lol. My dr isn't calling me cured we are watching and seeing. I feel better of abx this past month, my numbers are coming down, but I still have tinnitus and don't feel 100%.
The only reason I am putting some stock in my test results was that I was such a high positive on all Lyme tests incl WB, Elisa, C6 peptide, PCR live blood and PCR live urine and numbers are dropping...my index is finally 2.50 (was over 5 for a long time.)

Marie said...

Sabrina...you didn't mention how long you've had Lyme ? If you just got it that may be a reason why you only have igm antibodies, because the igg maybe haven't been produced yet.???
Thanks Lyme MD for clarifying the igm concept that the body may be reacting to an ongoing infection as if it was an early acute infection. This has me thinking because my first negative Lyme tests after 11 mos. of tx showed only 1 igg, the following mos another one reappeared after I stopped abx tx....I also got another igg band back as well during that mos (went from 1 band to 2igg) overall still hopeful considering how high my positive was.

ginny said...

I was bit by a tick almost 10 years ago now, I found it buried in my leg. I was diagnosed with lymes on severe clinical symptoms immediately following the bite. I was given 2 weeks of doxy. I have never felt right since that day. I have literally every symptom in the books although I have never tested positive for lyme. Until my bloodwork came back 3 days ago. I tested positive for IgM p23 but no IgG. I have been to EVERY specialist that exists in the world for a slew of symptoms only for many of them to patronize me and tell me it's anxiety, or to diagnose me with vague diseases such as autoimmune arthritis and chronic fatigue. Any idea what significance this positive IgM p23 has without another band present? Is this finally a break in the mystery that has become my body?? Any insight would be not only helpful but words can't describe how desperate I am to figure out what's wrong with me! thanks in advance!

Lyme report: Montgomery County, MD said...

The 23 band shows a reaction to a protein on the exterior of the Lyme spirochete, Osp C, Outer Surface Protein C. This protein is found only on the Lyme spirochete. If this result was for any other disease other than Lyme disease doctors would take note. Please consult with a physician knowledgeable about Lyme disease.

Tina Newfield said...

I had Lyme in 2002 & 2010. Antibiotics were a success. Neither time did I find a tick but ticks seem to be the only way Lyme can contracted so I guess I had a tick bite. I was relatively healthy the 8 yrs in between both episodes. I just went for my yrly. physical. I feel the healthiest I've felt in the 48 years of my life (Training for a half marathon..). The dr ran a Western Blot, they are doing this automatically now as lyme is so prevalent in my area. He said it came back + bcuz IgM P23 was present (the only band present). Only IgG P23 & 18 are also present. He wants to treat me for Lyme. Why? ALso, I have psoriasis (auto imm.) can this cause IgM p23 to be present?