Course of Antibody Response in Lyme Borreliosis Patients before and after Therapy
1Department of Dermatology and Venereology, Medical University of Graz, Auenbruggerplatz 8, 8036 Graz, Austria
2Institute for Medical Informatics, Statistics and Documentation, Graz, Medical University of Graz, 8036 Graz, Austria
2Institute for Medical Informatics, Statistics and Documentation, Graz, Medical University of Graz, 8036 Graz, Austria
Received 27 September 2011; Accepted 27 October 2011
Academic Editors: A. Clayton and S. Devi
Abstract
The early immune response (IR) in European Lyme borreliosis patients has not yet been studied in detail. The aim of the study was to analyse retrospectively the antibody development in 61 erythema migrans (EMs) patients depending on the duration of infection from tick bite by using a whole-cell lysate B. gariniiimmunoblot. The evolution of antibodies proved to be undulatory in untreated patients with two peaks for IgM at weeks 5 and 9 and for IgG at weeks 4 and 8. The analysis of IR courses after therapy identified patients constantly seropositive or seronegative and patients with repeated seroconversions with a switch, disappearance, or reappearance of anti-23 kD or anti-39 kD antibodies during the one-year period. We suggest that the antibody production in EM patients may be missed due to an undulatory IR. This phenomenon might be an as yet insufficiently researched aspect in Lyme borreliosis.
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extract from study
Although the undulatory character of the IR before therapy in our patients could not be determined in every single patient, the findings after treatment might reflect a similar situation also in untreated patients before therapy. So, we suggest that a single serological finding is a snap shot and gives evidence of an infection. On the other hand, the true infection might be missed by negative IR, as might be the case in the ~40% seronegative EM patients.
Serological findings do not distinguish between active and previous disease. Borrelia DNA can persist in urine for even 1 year after treatment [11], and antibodies to Bb may persist for up to 20 years after appropriate therapy [12]. Bearing in mind the characteristics of cyclic patterns in other bacterial infections, the undulatory IR noted in our study may be an as yet insufficiently researched aspect in Lyme borreliosis.
I found this to be an interesting study given that I think even Barbara Johnson of the CDC here in the US has said that if a blot shows new and expanding bands that that is evidence that a patient may have a new infection.
ReplyDeleteWhether one is in the US or Europe, I think a lot of what follows applies when it comes to Borrelia infections...
In the original CDC Lyme disease criteria that was posted in the 1990s - guidelines people don't talk about much these days, having focused on the 2006 IDSA guidelines - the following items were the laboratory criteria for diagnosis:
- Isolation of Borrelia burgdorferi from clinical specimen, or
- Demonstration of diagnostic levels of IgM and IgG antibodies to the spirochete in serum or CSF, or
- Significant change in IgM or IgG antibody response to B. burgdorferi in paired acute and convalescent phase serum samples
It's this last item that is missing from the current guidelines which I think definitely needs to be encouraged and restored, given how many people I have heard stories from about having been bitten by tick, even having had the rash - and a negative ELISA.
This is the current set of CDC criteria used:
Positive Culture for B. burgdorferi, or
Two-tier testing interpreted using established criteria [1], where:
a. Positive IgM is sufficient only when ≤30 days from symptom onset
b. Positive IgG is sufficient at any point during illness
Single-tier IgG immunoblot seropositivity using established criteria [1-4].
CSF antibody positive for B. burgdorferi by Enzyme Immunoassay (EIA) or Immunofluorescence Assay (IFA), when the titer is higher than it was in serum
Now, the rash alone is enough to merit treatment - no blood test is required under the current criteria for treatment as the EM is a clear diagnostic.
But if the rash is questioned as being an EM rash or absent, then blood tests are what doctors are going to fall back on - and follow up testing is necessary because of this undulatory immune response.
In this sense, the current CDC criteria are too narrow and restrictive because they do not take this undulatory immune response into account - but the original criteria may have been more likely to catch the wave, so to speak. One must catch the immune system when it is actively reacting to the infection and get the snapshot at the right time.
Something I read a while ago suggested (sorry, would need to dig the citations up - not coming to mind at the moment) that the immune response produced in waves comes in tandem with Bb's antigenic variation. That is, that as Bb changes its outer surface proteins, new antibody responses are produced to those proteins. The first "phase shift" can occur within days to a couple weeks after infection, and if it's a strain which rapidly disseminates, it's more likely to shift earlier on.
I know there are studies where non-Bb Borrelial strains (like B. turicatae) disseminate and differentiate their proteins depending on location in the body (See: http://www.ncbi.nlm.nih.gov/pubmed/11292762) and although this is a SCID mouse study, it can indicate what may happen with other Borrelial strains in humans.
This definitely requires more study. And it galls me that knowing what we knew about Borrelia ages ago, that researchers didn't explore this particular issue a lot more closely years ago.
Thanks Camp Other for your comment - here in the UK it is difficult to even get tested for Lyme Disease many doctors are oblivious to the possibility even when presented with the classic symptoms of tick bite and bulls eye rashes.
DeleteIt is also next to impossible to get a view of the detailed test results showing the banding - I haven't spoken with anyone yet who has and not even sure FOI would produce the full details so tightly do they control things.
Another problem anyway is getting repeat testing here in the UK, even initial testing can be difficult to get done if the history doesn't suit our 'expert' microbiologist.
However a good bit of news recently where a patient went to a hospital for ELISA and was told by Micro biologist ( not our Southampton Microbiologist) that the test was no use and didn't mean anything if it was negative.
When I was tested I'd had several weeks antibiotics and over a year of high dose steroids for PMR diagnosis so no surprises they were negative.
Still we live in hope that the blinders will come off this denial sooner than later.
"[...] here in the UK it is difficult to even get tested for Lyme Disease many doctors are oblivious to the possibility even when presented with the classic symptoms of tick bite and bulls eye rashes."
DeleteIf doctors in the UK and US want to see fewer chronic Lyme cases, they need to get their act together and begin treating upon seeing an EM rash. They're not only neglecting patients and leaving some of them to a life of years of disability - they're creating more work for themselves in the form of difficult and hard-to-diagnose and treat patients. Earlier diagnosis and treatment really is best. Essential. Even waiting weeks to a few months after the tick bite can lead to complications.
"It is also next to impossible to get a view of the detailed test results showing the banding - I haven't spoken with anyone yet who has and not even sure FOI would produce the full details so tightly do they control things."
How do you get your results? Can you only receive them from a doctor or can you contact the lab directly for results? Different countries/regions have different regulations concerning test result access.
Does the test manufacturer produce an assay report that shows the bands even if they do not usually pass that information on to the doctor? I'm wondering if you can petition the test manufacturer to pass the bands on to all doctors and to get that info as part of your results instead of just "negative, positive, or equivocal"?
"Another problem anyway is getting repeat testing here in the UK, even initial testing can be difficult to get done if the history doesn't suit our 'expert' microbiologist."
Are you talking about SOC at Southampton? I've read her reports, saw her speak at the IOM workshop in 2010. She seemed to have this speech prepared that sounded very supportive of patients while at that conference - but in other venues, she came across as less understanding and supportive. I've been trying to learn more about her role in the UK/NHS as regards Lyme disease.
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Delete"However a good bit of news recently where a patient went to a hospital for ELISA and was told by Micro biologist ( not our Southampton Microbiologist) that the test was no use and didn't mean anything if it was negative."
There are a number of publications from both US and European researchers that indicate that seronegative Lyme disease does and can occur. I think that if a patient has history of a tick bite and symptoms of Lyme disease but a negative ELISA that a doctor should take the empiric approach and treat with antibiotics and see if the patient improves. And if a doctor is concerned about having some test result, that a Western Blot taken when a patient is not on antibiotics and is having a "flare up" of symptoms is recommended in order to catch a snapshot at the best time for a positive antibody response. It means having patience with patients, and having a long follow-up process - but that's better than no follow-up at all and writing off a patient's condition as some non-treatable condition when it may not be.
"When I was tested I'd had several weeks antibiotics and over a year of high dose steroids for PMR diagnosis so no surprises they were negative."
It's a tricky situation. Often people will find that after they commence antibiotics and retest, they will have a positive test when they hadn't had one before. Steroids, on the other hand, tend to be far more suppressive on the immune system and that can result in a negative test. I'm sorry you had to take steroids and for that long - the side effects can be irritating and long term use is contraindicated for Lyme disease. (There has been some debate as to what amount and kind of steroids can be used when one has an active Lyme infection - even to the point where topical steroids are questioned.)
"Still we live in hope that the blinders will come off this denial sooner than later."
I hope so. I am often astonished that doctors are not even meeting the minimum expectations and guidelines of the CDC and IDSA for diagnosis and treatment for Lyme disease. What gives?
Lyme Disease Action discusses this on their website here http://www.lymediseaseaction.org.uk/latest-news/immune-response-develops-in-waves/
ReplyDeleteI wanted to say this, and somehow it slipped my mind: "I found this to be an interesting study given that I think even Barbara Johnson of the CDC here in the US has said that if a blot shows new and expanding bands that that is evidence that a patient may have a new infection. Not only this, but it can be evidence of a current infection progressing." That last part being the more important part.
ReplyDeleteI posted the presentation to the IOM Workshop by SOC on an earlier post http://lookingatlyme.blogspot.com/2010/10/microbiologist-from-uk-at-iom-workshop.html
ReplyDeleteI have a lengthy exchange going on with Dept Health through my MP, the basis of which is the contradictions said in that presentation with that said in the Anti science paper which she co authored. The D of H blindly support SOC and there are many inconsistencies in their replies with no account paid to any research links I have sent. However they catch themselves out not infrequently, one day those letters will be used to expose their deliberate denial of what science is available - leaving so many to suffer un necessarily.
However they write that they support the James Lind Alliance and are working with Lyme Disease Action in the joint research with JLA - Hmm! I wonder whether they will still be saying that when the research results are all in.
History will judge all those who have denied this disease in its chronic form - causing so much suffering.
The Resolution of Relapsing Fever Borreliosis Requires IgM and Is Concurrent with Expansion of B1b Lymphocytes1 http://www.jimmunol.org/content/170/7/3819.short
ReplyDeleteDr. Tom Schwan PHD of Rocky Mtn Lab, Hamilton , Montana
informs us that
For RELAPSING FEVER BORRELIA group, the infection in man
is FINALLY CLEARED from HUMAN BLOOD
BY
ANtibodies of Which CLASS???
[ Are you ready to receive DR. Tom Schwan's 27 years of expertise on RFB knowledge??}
did you guess that the CLEARING of RFB -[ Relapsing Fever Borrelia]Borrelia from Human blood is finally achieved by....
IgM class antibodies and IgM antibodies to RF Borrelia group are the Sole Antibody Class responsible for
clearing the human host from Relapsing FEVER Borrelia.
You are correct!!!
Now we return to the CDC guidelines for interpreting the significance of IgM CLASS antibodies in Lyme borreliosis http://www.lymeneteurope.org/forum/viewtopic.php?f=7&t=5237