Thursday, December 4, 2008

Chronic Lyme and poor IgG response

Chronic Lyme patients frequenly have a poor antibody response as seen on a Western Blot. Frequently there is a predominance of IgM bands. IgG responses may be sparse or absent. Patients who test positive according to the national CDC surveillance criteria usually do so by meeting the IgM criteria. This is still seen in patients who have had Lyme disease for many years. IgM antibodies are the "quick and dirty" response of B lyphocyte antibody production. These are churned out early after antigen (Lyme protein) presenation to helper T cells. IgM antibodies are not particularly effective. They are larger and do not bind all that well to target antigen proteins. These antibodies may show less specificity and be more like to induce autoimmune reactions due to molecular mimicry. The same B cells or plasma cells that produce IgM antibodies (immunoglobulins) also produce IgG antibodies. A molecular switch is pulled after the initial period of infection. IgM production is shut down. The B cells or plasma cells now kick into gear manufacturing IgG antibodies. These smaller, more precise antibodies bind better to the target proteins. It takes time for the "antibody factory" to gear up and make these preferred antibodies. This is why the Immune system provides this two punch approach to dealing with germs. These (IgG) antibodies are typically associated with immunity to a particular disease. This is for example the response one would expect to see after an effective vaccine.

With this in mind, I have started paying attention to the balance sheet, as it were. I compare the IgM and IgG responses seen in various patients. Patients with a predominat IgG response fare much better in general. For example, I saw a patient yesterday who had presented with severe symptoms of longstanding disseminated Lyme disease about 18 months ago. He responded remarkably well to treatment, despite an advanced age of 76. Therapy was stopped after one year. He experienced a prompt therapeutic response followed by full remission. Six months later he reports
robust health. I glanced at his Western Blot. He had 7 IgG bands and zero IgM bands. His immune responses to Lyme were appropriate. Unfortunately this is the exception not the rule.

Patients with predominant IgM responses generally do not respond nearly as well to therapy. Therapy is required for a much longer period of time. These patients require more creative combination therapies and attention to co-infection.

It is not essentially a host response issue. Patients make normal IgG antibodies when exposed to other infectious diseases. There is something unique about Lyme disease. Somehow it short circuits the switching of IgM and IgG antibodies.

There is a subset of patients whose immune systems apparently go beserk when exposed to Lyme. Dr. Kilani reports Western Blot strips in which the entire strip, IgG and IgM turn black. He suspects these patients may have autoimmune hyper-reactivity. I have no experience to support or confirm this observation. I will keep a look out.

11 comments:

Eric said...

for what it's worth...

After 10 yrs undiagnosed, a low CD-57 prompted me to get an Igenex western blot (positive@41 and indeterminate on a few others). My MD then did an antibiotic challenge for a urine DNA test. A week later I ran a westernblot at Clongen, which resulted in a positive IgM (at 41, 23, 66, 75) and only an IgG hit at 41.

Perhaps the antiobiotic challenge triggered the IgM into action? Or perhaps Clongen is more sensitive than Igenex?

Thanks for your wonderful blog! Keep it up. You are really helping push forward the attack on Lyme

Seibertneurolyme said...

But what about those patients who are completely seronegative? How do they respond to treatment?

Hubby has been ill for 7 years. Has had many western blots from IGeneX, MDL, Stoney Brook and other labs. Only once did he even have any bands show at all. A positive band 41 one time -- everything else totally negative probably 15 times in total.

He did have 2 positive recombinant antigen tests from MDL -- test no longer performed. Also one positive PCR from IGeneX. And the Immunosciences test (Immunoserology of Lyme) which was sold by the now closed lab and is offered by Neurosciences Lab was technically negative although it showed reactions to both IgG and IgM outer surface proteins A and E and basically everything else included on that test panel.

About the only test hubby has not had is the C6 peptide test.

Do you know if people who have B. garinii or B. afzelii instead of B. burgdorferi have any bands show up on Western blots?

Staris said...

LymeMD - so can you extrapolate that those lyme patients with poor IgG response would receive greater benefit from IVIG? I know about your inability to prescribe, but if other conditions warranted - would you expect a significant positive effect?

May explain why some lyme patients with IVIG see marked improvement while others (maybe better responders) don't see as much of an improvement.

As always - thanks for you continued dedication.

bitten said...

I know that I had two EM rashes and my work keeps me in highly infested areas daily. My diagnoses was easy. Others that work with me have gotten Lyme but I have been the sickest by far. I tested negative (completely) for over a year then an antibiotic challenge was done. I had a herx reaction like nothing I have ever felt before. Doc says I "sero-converted" IgM was then positive by CDC standards with 7 or 8 bands; IgG positive by IgeneX but not CDC. I've had positive PCR now from knee fluid. Positive everything. I wonder if I ever would have tested positive (and I went through the very classic Lyme symptoms to include becoming totally disabled mentally and physically) if the antibiotic challenge had not been done and why does that cause a sero-conversion? Doc has found an individualized treatment plan and I have been getting better. Slowly but certainly better. Lyme is certainly the hardest thing I have faced in my life and I wonder why some of us do not produce the appropriate response when we have been healthy all our lives so our immune system has functioned well against other attacks? I will be in MX soon. Since antibiotics are OTC there I will see if they have IVIG. Even if it is IV or IM, if they have it I will buy it.

Lyme report: Montgomery County, MD said...

If a patient is seronegative after more than a year I think the diagnosis needs to be reconsidered. Positive test results from labs which have been disputed need to be considered with a grain of salt. The strains of Borrelia due vary but there should still be some cross reactivity. The C6 peptide Lyme antibody test should be included. If a patient with no evidence of Lyme responds to antibiotics it doesn't mean that the response is a placebo effect. Other chronic infections have been shown to mimic Lyme disease. These include Mycoplasmas and Chlamydia pneumonia. If on the other hand, there is no objective evidence to support the diagnosis of Lyme and there is positive response to antibiotic therapy, the diagnosis needs to be re-considered.

The general medical community overlooks Lyme disease as a cause of many symptoms.

If "LLMDS" believe that Lyme disease is the cause of all chronic medical symptoms this can be equally detrimentaly- or worse.

Patients have been diagnosed with Lyme disease when they in fact had cancer and other serious illnesses.

Caustion: Do not put patients into a Procrustian bed (Greek mythology).

tickitytack2 said...

this totally decribes my husband who has been ill for 20 years, misdiagnosed with chronic fatigue. he tested igenex igm cdc positive and igg negative.
he is difficult to treat and went downhill on months of abx. he's been seeing an llmd for 8 months now and started iv rocephin 2 months ago- beginning to improve. insurance denied 2nd month of iv tx and questioned his chronic lyme diagnosis stating that he would have tested igg positive with chronic lyme and discounted his diagnosis because it was igm positive.
we plan to appeal. do you know any current articles/research with this info for our appeal?

Starlings Preschool said...

Doc, have you seen Lyme WBs cycling between positive IGM and IGG? I was told recently by my LLMD that moving from IGM to IGG positive was a good sign (along the lines of your patient who responded well to tx and had a positive IGG only), but then was also told that the WBs cycle back and forth.
True in your experience? Meaningful?

sci-ed said...

what of those with hypoIGG as in CVIDS??? these people dont have much IGG production to begin with and that may confound Lyme et al treatment


btw many who have done IvIG wasnt with a Lyme dx--and at over 5,000 US$ per dose taken every 3-4 weeks for up to 6 month cycles I cant imagine them paying out pocket--so the diagnosis had to be for another condition

as it happened they also coincidentally had Lyme and after IVIG possibly was able to utilize the abx better

and btw, there are MANY pts with seronegativity even by the fringe labs and yet quite infected and ill with TBIs ( tick borne illnesses)

I was/am one of them--ZERO chance of reinfection or re exposure and year 3 into treatment despite seronegative the entire time-I FINALLY began to show antibody response and also a 5 ring bullseye rash!!

then again year 6 or 7,after 2 yrs remission and off all meds, return of sx and retreatment, another multiple rash in a different area about 3 weeks after restarting abx due to that relapse of symptoms

it wasnt until year 11 after yet another short remission that Bartonella sx reared and included typical rash/streaks with sweats etc and yet NEGATIVE tests

started meds presumptively and wham week 2--positives on antibody tests!!!

I thank God my Drs at the time didnt believe the seronegativity myth and instead trusted the sx pattern and my experience/ symptoms and their own judgement!!

Paula said...

My daughter was bitten by a tick and three days later we traveled to Romania.I tested her here in ROmania exactly 4 weeks later and her IGM was negative but IGG was high.They told me that means previous exposure to lyme disease. How is that possible.My daughther was never bitten by a tick before.Not that I have knowledge of. Does that mean she has chronic Lyme disease, and was never treated? What should I make of all this? I asked the Romanian doctor and he said that in the absence of symptoms, he doesn't recommend any other testing - especially since her IgM was negative too therefore no acute infection. Please advise me on this and e-mail me at paularosca@ymail.com . Thank you!

walsh24 said...

I was diagnosed with lyme on Sept 2011, during that summer I was gardenen. Around June I noticed a round rash on my leg. It was not a bullseye, so I dismissed it. A few weeks later, i developed a fever and had headaches. In July my knees hurt but I was working out alot so I blamed that. In late August, my symptoms got worse my chest was numb. My doctor tested for lyme and it was positive for igm bands 23, 41 negative Igg and positive igg parvo. I was treated with 28 days of doxycycline. The first week was hard after that I felt better. A year later I had a sudden onset of fatigue, tingling burning feet, aches so my doc tested again for lyme. Same results.... What'sgoing on? I should show positive igg not igm. Please advise, I am on another 28 days of doxy, last week was so very hard.

walsh24 said...

Please excuse spelling errors, i am on my phone