Sunday, February 14, 2010

The IgM question: Is it chronic Lyme disease?


Many patients have been told by their physicians they do not have chronic Lyme disease because Western blot antibodies are in the IgM class, not the IgG class. The doctors themselves may be confused -- or adamant. The adamant ones very likely don't believe chronic Lyme exists. If you, on the other hand, believe chronic Lyme is real, you may want to discount opinions proffered by those who do not share those beliefs.

Lyme acts differently immunologically than many other germs. Patients with only IgM antibodies may have Lyme and or/ chronic Lyme.  In the typical scenario of  antibody response to infection the immune system makes IgM antibodies in early infection and then makes IgG antibodies in late infection. As the amount of IgG increases IgM decreases and then goes away.  This is not always the case. Lyme is a clear exception to this rule.

Peer reviewed medical studies have contributed to the confusion. Selection bias inherent to published studies is one problem.  The only patients selected for NIH sponsored clinical trials have had IgG, not IgM antibodies. One investigator, Brian Fallon, who treats a lot of Lyme patients, found it challenging to find patients with the 5/10 IgG band requirement; less than 5% of his patients fulfilled the study entry requirement. All studies require certain criteria for inclusion in the study. These criteria were used for standardization and in no way suggest or prove that a particular IgG response is needed for the diagnosis.

A large chunk of chronic Lyme patients have only IgM responses. Some have mixed IgM and IgG responses. In some cases IgG responses are favored and in others IgM.

Those from the no-such-thing as chronic Lyme camp stake out the position that persistent IgM responses without later production IgG antibodies represent false positive responses.  Patients with only IgM responses are told that they in fact never had Lyme, or they may be told they have Lyme but it must have a new case.  Science tells us something else. Some patients make only IgM antibodies. And it is known that IgM and/or IgG antibodies may persist for years after acute infection.(Steere). The CDC has not been helpful.  The CDC two tier test, ELISA followed by Western Blot standard was developed for surveillance, not clinical diagnosis. The claim that the test lacks accuracy in early Lyme but is virtually 100% accurate in late stage Lyme is crazy and has no basis in science -- or published evidence. This unfounded statement unfortunately lends credence to the Lyme deniers who push the falsehood that IgM bands equal false positive.

IgeneX has published its finding that 2 specific IgM or IgG are diagnostic of the disease, stage of the illness not withstanding.  Aucott has found that 20% of patients with treated acute Lyme are unable to produce IgG antibodies, likely a genetic variable. Steere published data showing persistence of IgM antibodies in late Lyme in the 1990s. This knowledge is not new.  Existing literature supports the idea that certain Western Blot antibodies are highly specific for Lyme. If specific antibodies are present it is unlikely they are the product of a false positive test, irrespective of antibody class.  When only IgM antibodies appear there is a alternate hypothesis. The persistence of IgM antibodies may suggest the immune system is "chronically" seeing Borrelia as an acute--new infection. This interpretation is applied by doctors in other situations. For example EBV. IgM EBV antibodies are frequently interpreted as evidence of reactivation of the infection.

Antibodies are the result of "humoral" immunity or acquired immunity. The immune system "reads" the pathogenic germ and turns the information over to the body's antibody factory. IgM and IgG antibodies are produced by the same cells: B lymphocytes. These lymphocytes may become plasma cells. The change from IgM to IgG is due to a genetically directed molecular switching mechanism. This class switching--IgM to IgG-- may not occur or occur poorly. We don't know why but these facts have been established by evidence based science.

In my experience, Lyme patients, on average, produce slightly more IgM than IgG antibodies. This may be hard to see since most IgM assays present limited data (few bands). Certain antibodies, for example: 18, 23, 31, 34, 39 41 and 93 are HIGHLY specific for exposure to Lyme bacteria and this is well described in many places.

Doctors known as LLMDs have know for decades that the IgM vs IgG class distinction does not apply to Lyme.

Addendum:  Antibodies are Y shaped molecules/proteins made up of heavy chain and light chains.  Some portions are variable and some portions are invariable.  Binding to antigen occurs when a variable portion at the end of one leg of the Y has a structure reconfigured (controlled by gene modification).  This is the part which is analogous to taking a key to hardware store to have it copied. A generic antibody is like the blank key. The key (specific antibody) is formed through a complex process. The same cells, B lymphocytes/plasma cells that make IgM antibodies also make IgG antibodies. When the class of antibody is changed it is referred to as isotopic switching.  Here is the critical piece of information: the key - the variable portion of the antibody is unchanged when IgM is changed to IgG. Rather an invariant heavy chain is swapped out. Meaning: the specificity of IgM antibodies is identical to the specificity of IgG antibodies. Remember, the immune system is controlled by mediators, cytokines. The switch from one class to the next is controlled by cytokines. IgM antibodies induce cytokines which differ from those of IgG antibodies. This is why IgM and IgG antibodies have different biological properties. The cytokines communicate with different parts of the most complex system (immune system) in the body outside of the brain and the wide array of moving parts are given different tasks. IgM signals are different from IgG signals. It should all work together for the most effective killing of unwanted pathogens. The operative word is should. 

Germs evolve. Germs are smart. If a pathogen can modify the signals and confuse the cells, if gives the highly motivated germ a leg up, a survival advantage, and we know that Lyme infection can modify cytokine responses. Maybe that is why isotopic switching, IgM to IgG fails for many patients. 

Take home point:  the part of the antibody that specifically binds to the antigen is 100% unchanged when IgM antibodies are replaced by IgG counterparts. 

If you suspect you suffer with manifestations of Lyme disease only an experienced knowledgeable doctor can make the diagnosis.

Please see other BLOG posts for more information regarding this issue.




38 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?

MrApplewine said...

The logical thing to do is test a patient with both the OspA nano-trap ANTIGEN test and the Igenex IgM 31 ANTIBODY test, with epitope confirmation. If they are both positive then you may have a valid theory for Igm 31 and broken immunity conversion to IgG.

Carla Roberta Peralta Menezes said...

My 14 years old daughter is a excellent athlete and A plus student. In her blood tests her Western Blot came positive IgM P41 Ab and IgM P23 Ab came positive. We were very concerned about it because she was born in CT and lived there until 3 years ago. So, we took her to LLMD who started the treatment and she has been taking Monocyclen twice a day everyday and Flucozolane twice a week and also other supplements as well as probiotics. She was very vibrant and well before the treatment, now she feels very fatigue and sad all the time... The Doctor also found out that she has C667T homozygous (Methylation Defect) and added some supplements for it. We also took her to a Infectious Disease Doctor who did not believe that she has Chronic Lyme and instruct us to stop the treatment. Now, we went back to the LLMD who wants to add another antibiotic to her regimen. We are very concerned and scared to which approach should we take? Please, any suggestions to maybe a less invasive treatment so we can combat this virus , so our daughter would never develop Acute Lyme Disease? Please, help us to make a decision about our daughters' treatment. Thank You so much!

LymeBeGoneFriend said...

Beating back Lyme is a long process and antibiotics/ methylation supports can be very useful, and it generally takes quite some time, during which the patient does not feel great, generally worse than before starting the therapy. That said it is worth continuing the regimen and trusting your LLMD. If you feel you need a second opinion, it is best to get a Lyme competent alternative practitioner eg LLND or another LLMD, but not another health practitioner who is not very familiar with this condition.

Remember that antibiotics work but have side effects and patient needs lots of good quality spring water to flush out kidneys during the treatment. Adrenal glands generally need support with Lyme also eg. methylated vit B's, liposomal vit C and zinc.

Generally recovering from Lyme can be about a two year process !

Hope this helps !

Info at said...

igM 23 showed and nothing else for me for 5 years of testing. Finally got treated and symptoms abated in first two weeks of antibiotics. It was certainly an active chronic infection. I'd love to see igG's show up but i'm not sure they ever will.

Cora Regina said...

I just got my test results back: IgM had 34 + (which of course the CDC ignores), 39 +, and 41 ++. IgG had 31 + (and more CDC BS), 39 IND, and 41 ++. Now looking for an LLMD, because my current holistic doctor isn't one and wants to run me through the herbal ringer and I just don't see silver and iodine helping.

PrimReaper said...

To whom would you direct me to see in North Carolina that understands the disease; as well as proper testing? Thank you.

PrimReaper said...

To whom would you direct me to see in North Carolina that understands the disease; as well as proper testing? Thank you.

The Oil Snob said...

I tested positive for IGG 41 and IGM 23,39,41 on the western blot. My husband thinks I don't have Lyme and wants me to do more testing. Which test would confirm? CD57, nanotrap antigen test, and igenex Lyme and confections are what we're are thinking about doing. Right now I am being treated for hplyori then my doc wants to start doxy and diflucan. I am waiting to get into a LLMD, hopefully soon.

Unknown said...

I am amazed at what i am reading !!I have been going thru the same exact thing ..my results are igm reactive 23 and nothing else so Dr's saying in negative ..have beenough to every dr under the sun and all are saying anxiety. ..in wouldn't give up cause I knew it's not anxiety ...finally a natural health dr decided ti treat me dir lymes based on my reactive blot 23 and took doxycycline fir 4 wks feel worse then ever ! My worst symptom is the dizziness I can't take it..I do have athritic pains and numbness Ringling in my hands and feet but the dizziness drives me insane I've become a compleltwly different person I want my life back !! Will I get it ...it's almost a year like this!!!

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Unknown said...

I am going through a very similar situation and would love to talk more. Feel free to contact me at snookie4123@aol.com or crystal blumberg on facebook.

Crystal Blumberg said...

I am looking for help or any feedback. I tested positive for two out of three bands Igm test and negative IGG test in 2011. Have had continued symptoms since then. In 2013 I had just a reactive band 58. 58 was not previously reactive as well as a low positive ana.In the last three years I have developed what they have finally diagnosed and psoriasis and psoriatic arthritis (because of terrible joint pain in the hands) Hearing from anone who might have any feedback at all would be so appreciated. Contact me on facebook or at snookie4123@aol.com

Karlee Weiler said...

I am looking for advice on whether to push for a lyme diagnosis or not. My trouble is, there aren't many LLMDs in my area so it will be an expensive process. After seeing so many other specialists and testing, my pocket is empty and don't want to waste any more money if it's just fibromyalgia (dx'ed in march 2017). Anyone with experience, please email me at kar25_50@msn.com
I've had two western blots with 23 and 41 igm positives both times and once with both 41 igg and 41igm antibodies. Thank you in advance!!

Linda Maran said...

I have been struggling with Lyme Disease for nearly seven years. I have had IGM and IGG bands. Mostly IGM 23 positive and IGG 41 and 47. Sometimes total negative bands but it doesn't last long.
After many courses of antibiotics for two to three weeks at a time and for one month another time, I decided to go to an Infectious Disease specialist. He tested me for Babesia, telling me I did not have Lyme Disease despite the test results. He said: "You've been treated." But I did test positive for Babesia but only in the antibodies and not in the smear test, so he said it was mild and put me on a malaria medication and Zithromax for one week. Even though I still felt sick afterwards he would not retest me. Instead I was told to go to a Rheumatologist who took every auto-immune test there is. All came out negative. He found that I have osteoporosis, which is not fun, but he too denied Lyme Disease, would not even look at my tests. He tested me with a PCR for Lyme which is a totally unreliable and it came out negative. Yet he ignored my positive band 23 I have a month or so earlier. I just had another Western Blot done last week and Band 23 IGM is positive. My doctor said it needs to be treated and prescribed Doxycycline again for two weeks. My knees hurt and I am very fatigued and I also have bad pain in my rib cage. So I guess I'll take the meds and see if I feel any better. I keep relasping. This is not a new infection because I have not gone up to my country house where I originally got bit. BUT regarding an LLMD. The one closest to me which is 1 1/2 hours, charges $800 for the consultation and $365.00 each monthly visit. Doesn't take insurance.(None of them do.) I think this is as bad as the MDs who will not treat Lyme. It weeds out folks who cannot afford treatment. So either way, we cannot get the proper care. It's really disgraceful. I am thinking after this to try what is called The Bob Beck Protocol. Using electrical and magnetic pulsing to kill bacteria in the blood with drinking some colloidal silver and lots of water to flush them out. The guy was a brilliant scientist. I wish everyone healing.

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