Friday, August 5, 2011

12 Antibodies linked to long-term Lyme symptoms

Nature has just published an article today on research which shows a relationship between post-Lyme disease syndrome and persistent infection.

Armin Alaedini at Weill Cornell Medical College in New York and his colleagues have found that patients diagnosed with post-Lyme disease syndrome have antibodies that suggest they carried the infection for an unusually long time. The finding, published in Clinical Immunology, might help the syndrome to be better understood, diagnosed and treated.

Bockenstedt is quoted in the article, saying, "This is the first study I've seen that shows some immunologic difference between someone who resolves their Lyme and someone who develops post-Lyme disease syndrome."

I highly recommend everyone checks it out, supporters and naysayers alike: The finding suggests that patients with chronic symptoms have experienced a prolonged infection.

Original Research:
Epitope mapping of antibodies to VlsE protein of Borrelia burgdorferi in post-Lyme disease syndrome. Abhishek Chandra, Norman Latov, Gary P. Wormser, Adriana R. Marques, and Armin Alaedini. Clin. Immunol. http://dx.doi.org/10.1016/j.clim.2011.06.005 (2011)

Comments:

I'm withholding any further comments on the content of the paper until I read the full text, but am open to discussing the contents and context of the article from Nature in comments.

READ MORE: http://www.nature.com/news/2011/110805/full/news.2011.463.html

12 comments:

  1. "This finding suggests that patients with chronic symptoms have experienced a prolonged infection, caused by microbes that have evaded the immune system by varying the epitopes they carry. As a result of these variations, the body makes new antibodies targeting the modified protein. The longer the microbe manages to keep changing, the more diverse its host's antibodies become."

    This is what I've been saying all along: Lyme disease antibody response is serologically progressive. As the bacteria engages in antigenic variation, the host produces new antibodies to them, and it could lead to immune system overwhelm.

    When there are new bands showing up on a test result - in concordance with what official mainstream scientific statements have been made - this is evidence of a new or recent infection.

    This idea is nothing new. Norris and Barbour, back in 1999:

    "These results further indicate that VlsE is expressed during infection and is highly immunogenic in the mammalian host, but that genetic variation may generate unique VlsE variants that are no longer fully recognized by the immune response against the parental VlsE."

    New variants. New responses.

    "If these antibodies are unique to people with chronic Lyme disease, it could lead to a test and treatments for the disorder, Alaedini says. It could also guide treatment of the disease itself. "If patients with an acute infection develop antibodies to these epitopes, perhaps they require a more aggressive course of therapy"

    What do you have in mind that people aren't already trying?

    'If an immune response problem leads to the syndrome, antibiotics won't help. "I guarantee you that if you tell a patient they won't feel better after antibiotics, they won't," Feder says. "We need to know what's going on."'

    Feder, what do you think of Alaedini's statement about aggressive treatment? If you think more antibiotics won't help, then please tell us what will and what treatment research you have been conducting. Thank you.

    ReplyDelete
  2. "I highly recommend everyone checks it out, supporters and naysayers alike: The finding suggests that patients with chronic symptoms have experienced a prolonged infection."

    What they are suggesting is chronic symptoms, after abx, are related to abs, generated by variable and/or invariable regions of VlsE, against "self". Auto-immunity.

    ChuckG

    ReplyDelete
  3. ChuckG,

    You said, "What they are suggesting is chronic symptoms, after abx, are related to abs, generated by variable and/or invariable regions of VlsE, against "self". Auto-immunity."

    Is that your statement based on the article, or is that your statement based on the paper?

    I'm getting more than one impression from the article, and as I've said, I can't really comment on the full text until I myself read it. I don't currently have an Athens account, so I have to get a copy elsewhere to read.

    From the article:
    "Armin Alaedini at Weill Cornell Medical College in New York and his colleagues have found that patients diagnosed with post-Lyme disease syndrome have antibodies that suggest they carried the infection for an unusually long time."

    I'm not sure how else to interpret this statement other than the presence of these antibodies suggest the patients with PLDS had an infection for an unusually long time. That implies a persisting infection. Those who want to start weighing in on the issue of whether or not they still have an infection after antibiotic treatment isn't the point I want to discuss on this statement - it's the "patients had an infection for an unusually long time" part.

    "This finding suggests that patients with chronic symptoms have experienced a prolonged infection, caused by microbes that have evaded the immune system by varying the epitopes they carry."

    Same goes for the above.

    "Some post-Lyme sufferers had varied antibodies against VlsE epitopes despite being diagnosed and treated early, says Alaedini. "That could mean they naturally have a different antibody response to the infection than most people; it could mean they weren't treated properly; or it's possible they were reinfected and the second infection was never treated," he says."

    Alaedini is speculating that any one of these issues could have led to the patients' conditions. Which to me means - it could be any one of these issues depending on the individual case. There probably isn't a uniform response for this and patients would need to be placed in specific subgroups for further testing.

    (more)

    ReplyDelete
  4. (ChuckG - more)

    "The presence of varied antibodies hints that the chronic symptoms could be caused by an ongoing inflammatory response caused by antibodies mistakenly reacting to the body's own proteins, Bockenstedt suggests."

    Now this - yes, this comment points out that she thinks this may be an autoimmune response at work.

    But then again, Bockenstedt says this next, and I'm not sure where that takes me:

    "The big question to me is whether this can lead to an autoimmune phenomenon," says Bockenstedt. "But if that were the case, I'd expect the disease to worsen without immune-modulating treatment, and it doesn't."

    So, is this an autoimmune phenomenon, or isn't? According to Bockenstedt, she doesn't think that's where it's headed because she thinks patients' symptoms would be worsening without immune-modulating treatment. So I surmise her observation of the PLDS population is that their symptoms are stable.

    My observation of patients' self-reporting is that they are not having stable symptoms, though - they have cyclical or worsening symptoms without antibiotic treatment.

    ReplyDelete
  5. If only people like Bockenstedt researching this could actually experience the illness themselves then they might not be so quick to hypothesise everything as auto immune. They could be wrong and should remain open minded until science can prove one way or another.
    In my symptoms I found auto immune only as being illogical why then would my body target specific areas for many many months and then progress to other areas when those original areas started to get better. Surely auto immune would suggest that many areas at any time would be affected.
    In simple terms when I get a rose thorn in my fingers the immune system knows to go to the site in order to fight the thorn invading my skin. My immune system is not hyper sensitive and doesn't go to other areas of my body when fighting against the rose thorn.

    This research supports my personal belief that the immune system is fighting something in the many areas of my body that have been affected. As I responded so well to antibiotics over about 4 years I remain of the opinion that in general antibiotics were fighting the remains of an infection. As nearly all my symptoms have now resolved certainly arthritis and muscle weakness it still supports the benefits of having fought a long term infection with antibiotics. The big question will be how well I remain now no longer on antibiotics.
    Bockenstedt is very much involved with the nay sayers camp so is certainly out to prove auto immunity from what I understand however I believe from just reading the article and not yet the research that this goes a long way in proving long term infection evading the immune system.
    I will be interested to hear a detailed summing up from such as CALDA or yourself on the whole paper.

    ReplyDelete
  6. I haven't read the full paper yet, but my initial interpretation was similar to Camp Other's. I also thought that this study paralleled Stephen Barthold's ongoing research: if you have a copy of Cure Unknown, look over chapters 36 and 43 of Part Three: A Search For Answers.

    -- Claudia

    ReplyDelete
  7. Joanne,

    Autoimmune disorders can affect people in different ways - it depends on the disorder. But to equate an autoimmune disorder with any infectious disease, one has to be sure of cause
    and effect.

    In your individual case, given that your symptoms have nearly completely resolved after 4 years of antibiotic treatment (and you've since stopped and symptoms have remained stable) - I, too, would be looking at the infection angle - or at least considering it even if I did not get infected with Lyme disease myself.

    I really do want to read the full text because it will shed more light on the authors' perspective - and I am not even certain they have a unified perspective, given statements made by Alaedini.

    I do wonder about what he said here, though:

    "Some post-Lyme sufferers had varied antibodies against VlsE epitopes despite being diagnosed and treated early, says Alaedini. "That could mean they naturally have a different antibody response to the infection than most people; it could mean they weren't treated properly; or it's possible they were reinfected and the second infection was never treated," he says."

    I can see how one could think that at least those particular patients with early treatment who still have persisting symptoms and a varied ab response to VlsE could have an immune system problem, were under- or mistreated, or were reinfected.

    But I also wonder about other possibilities: What if specific strains of Borrelia burgdorferi are more likely to lead to certain VlsE responses in the immunocompetent host? What if some strains disseminate more quickly and generate more serotypes quickly, diversifying in each organ system as relapsing fever does?

    (more)

    ReplyDelete
  8. (For Joanne (or anyone, really) - more)

    I also know that coinfection can affect the immune system's ability to clear Bb - documented with Babesia coinfection for certain, which I've had so I've looked at it the most. So isn't it possible a coinfection or two couldn't also affect results in an individual patient? I think so.

    That said, thinking about Alaedini's statement has me thinking of these studies...

    I look at something like this study:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC308929/
    Infection and Inflammation in Skeletal Muscle from Nonhuman Primates Infected with Different Genospecies of the Lyme Disease Spirochete Borrelia burgdorferi
    Diego Cadavid, Yunhong Bai, Donna Dail, Marie Hurd, Kavi Narayan, Emir Hodzic, Stephen W. Barthold, and Andrew R. Pachner

    and this study:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC97336/
    Conservation and Heterogeneity of vlsE among Human and Tick Isolates of Borrelia burgdorferi
    Radha Iyer, John M. Hardham,† Gary P. Wormser, Ira Schwartz, and Steven J. Norris


    "Although all isolates contained sequences that hybridized to the vls probe, only 10 of 22 yielded a 660-bp, vlsE-specific PCR product (Table ​(Table1).1). The most likely explanation for this finding is that the sequences in the region of the primers (based on the B31-5A3 vlsE sequence upstream and downstream of the central cassette) were divergent in the strains where amplification was not obtained. Indeed, the vls sequences reported for the North American B. burgdorferi isolates 297 (6) and cN40 (S. Feng and S. W. Barthold, unpublished data) are only ~40% identical and ~60% similar to the B31-5A3 sequence; many of these sequence differences occur in the invariant sequences outside the variable regions. Attempts to amplify vlsE from the cN40 strain using a variety of primers based on the B31-5A3 sequence have been unsuccessful (M. B. Lawrenz and S. J. Norris, unpublished data)."

    I keep wondering why the hell N40 isn't studied more. I think it's one of the Type 1 infections of Bb which is more virulent than others.

    (By the way, Steven Norris' work is really the research to look at to get more of a grip on the VlsE locus and genetic exchange with silent cassettes... he knows a lot about this.)

    Okay, the above study is from 2000. Maybe we need to look at this more recent one:
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772371/ (full text)
    Borrelia burgdorferi Sensu Lato Species in Europe Induce Diverse Immune Responses against C6 Peptides in Infected Mice
    Inke Krupka, Jens Knauer, Leif Lorentzen, Thomas P. O'Connor, Jill Saucier, and Reinhard K. Straubinger

    Read about the C6 antibody results. Different strains produce different levels of antibody response, anywhere from strong and growing over time (Bb N40) to weak (B. afzelii PKo) to undetectable (B. valaisiana or B. lusitaniae strains).

    C6, by the way, is a peptide that is analogous to IR6 which is an invariable region (IR) which if part of the VlsE protein. IR6 is highly immunogenic and using C6 blood tests is supposed to improve their accuracy for detecting infection from different strains because IR6 is found in all Lyme Borrelia at all life stages.

    ReplyDelete
  9. Quote from CO's entry: "My observation of patients' self-reporting is that they are not having stable symptoms, though - they have cyclical or worsening symptoms without antibiotic treatment."

    My interpretation of this observation / reporting is: They probably use ß-lactam ABs (ceftriaxone...), which is said to drive B.b into an insensitive "spore" (cyst?) form.
    Over time some of those "spores" will revert to normal B.b, multiply - and of course the immune system will start to fight, cause inflammation -- and signs and sympoms, new SUFFERING.

    So if it's not possible (at present, as far as I know) to get rid of the spores, the only logical way to PREVENT SUFFERING is to "hit" reverting and dividing / multiplying B.b even before new inflammation causes trouble.
    And it would be reasonable to avoid ß-lactames if they drive those multiplying (reverted) B.b right back into the "spore" form, which would perpetuate the problem ad infinitum, or rather until death of the host of the infection (or until the time a sound therapy for eradication of all B.b - including "spores" / cysts... - is found and successfully applied).

    I suggest to try oral doxy for "preemptive" fight against reverting B.b.
    I suggest not to use it continuously, but in a "pulsed" scheme. That's not my idea, but the idea of microbiologist Prof. Vera Preac-Mursic (formerly at the LMUniversity at Munich).
    With me this approach has worked for more than 15 years: after ceftriaxone in 1993 and 1995 (and a few other - oral - ABs) I started with a first course of doxy early in 1996, was really surprized that my cardiac arrythmias disappeared after full 5 years - and over several years devised a "pulse" - interval scheme for me.
    (See my comment to the "Finding the Right Treatment" entry for more info.)

    I'm still waiting for somebody to comment this approach, C O or anybody else.
    My arguments could be wrong, ivalid, illogical... If not: any arguments against giving my approach a try?
    (Another LD victim told me doxy is her life insurance, has been for more than a dozen years. And there have been successful pilot studies with mino(and doxy)cyline in MS, which almost certainly is a severe (demyelinating) form of neuroborreliosis.)

    To me that's enough evidence to give my approach a try (backed by the Preac-Mursic proposal), but of course I am biased...
    chen-men

    ReplyDelete
  10. Chen-men,

    In response to your comments:

    "Quote from CO's entry: "My observation of patients' self-reporting is that they are not having stable symptoms, though - they have cyclical or worsening symptoms without antibiotic treatment."

    My interpretation of this observation / reporting is: They probably use ß-lactam ABs (ceftriaxone...), which is said to drive B.b into an insensitive "spore" (cyst?) form.
    Over time some of those "spores" will revert to normal B.b, multiply - and of course the immune system will start to fight, cause inflammation -- and signs and sympoms, new SUFFERING."


    Please reread the bolded part of my statement above. No beta-lactam antibiotics were involved in the making of that statement.

    "the only logical way to PREVENT SUFFERING is to "hit" reverting and dividing / multiplying B.b even before new inflammation causes trouble.
    And it would be reasonable to avoid ß-lactames if they drive those multiplying (reverted) B.b right back into the "spore" form, which would perpetuate the problem ad infinitum, or rather until death of the host of the infection "


    Here is where one of the hypotheses about Borrelia gets interesting: One must treat the infection when bacteria are dividing. But they are slowly dividing, and divide much more slowly than other bacteria divide. If - as Barthold and Embers have speculated - some of these spirochetes are persister cells, then it wouldn't matter if we threw antibiotics at high doses at them constantly. They're tolerant. They will just shrug them off; the antibiotics will not affect them. The antibiotics will kill off spirochetes which are not persisters, though.

    Persisters can leave their persister state and antibiotics can work on them. This is one reason why pulsing antibiotics has bee speculated to help some patients. But pulsing has to be done mindfully and properly, otherwise the patient is put at risk and antibiotic resistant organisms can develop. The resistant organisms are not necessarily Borrelia, by the way - they are OTHER bacteria such as staph. One can develop MARCONS after antibiotic use - Multi Antibiotic Resistant COagulase Negative Staph infections, which often show up in the sinus cavity.

    One has to design and monitor treatment very carefully. I would like to see someone do a targeted pulse therapy study.

    (more below)

    ReplyDelete
  11. For Chen-men (cont'd):

    "I suggest to try oral doxy for "preemptive" fight against reverting B.b.
    I suggest not to use it continuously, but in a "pulsed" scheme. "


    See above. This is also how Pam Weintraub claimed to have gotten past her chronic Lyme disease.

    And it should be noted, here, that there are two existing realities I've mentioned regarding Lyme disease treatment:

    One is that there are doctors who are willing to treat patients empirically and experimentally - willing to try different antibiotic treatment schedules and dosages and see how patients respond, and

    Two is that there is a dominant model of scientific research which is hesitant to put patients in the role of guinea pigs without conducting formal treatment research providing evidence a specific treatment is effective in the context of a study and/or clinical trial.

    I personally would like to see the development of a third model of treatment research, and that is to give doctors a certain amount of flexibility in treating patients with chronic conditions and have an independent party uphold these doctors to certain standards and protocols so that they become participants in multi-clinic clinical trials. This sort of model would be similar to those at Stanford University who conducted studies on low dose naltrexone on fibromyalgia patients. Patients were well characterized, patients were treated, and a report was made.

    (more below)

    ReplyDelete
  12. For Chen-men (cont'd):

    "With me this approach has worked for more than 15 years: after ceftriaxone in 1993 and 1995 (and a few other - oral - ABs) I started with a first course of doxy early in 1996, was really surprized that my cardiac arrythmias disappeared after full 5 years - and over several years devised a "pulse" - interval scheme for me."

    I'm glad you've found something that works and you have improved. Thing is, what if other patients have tried your approach and it did not work for them? Would you suspect that their symptoms are due to a tickborne coinfection such as Babesia or some other condition? I ask, because over the years I've observed different patients try different treatment schedules, and some report improvement and others do not. I don't know what to tell them, and I really cannot advise them what is best to do in their situation as I am not a doctor and do not know their full medical history and comorbidities - plus not enough is known about patients with persisting symptoms to begin with because we're not studied thoroughly. Lyme disease has been studied a lot, a number of coinfections haven't been studied much at all, and patients with persisting symptoms aren't studied anywhere near as much as patients with acute cases of Lyme disease.

    "I'm still waiting for somebody to comment this approach, C O or anybody else.
    My arguments could be wrong, ivalid, illogical... If not: any arguments against giving my approach a try?"


    Well, others have indeed tried using doxycycline, tetracycline, and minocycline longer term and pulsed - if one is to accept what patients have self-reported in their own blogs, and what Dr. Donta has done in his practice. Some ILADS doctors I know of have prescribed such drugs for their own patients as well.

    I've commented elsewhere on this blog about doxycycline. If you're asking me why I personally haven't mentioned trying this for myself, keep in mind that there may be more than one answer here: 1) I might be allergic to doxycycline, in which case, proceeding with such a plan would be a Bad Idea for me; 2) I might be more private in regards to how I individually treat my condition, because I don't want to suggest to others that what works for me will in fact work for them - there is no guarantee that it will; 3) I might have found something else which is helping me personally but can't in all good conscience recommend it until there's more evidence it works (and evidence can take different forms here - not necessarily needing a clinical trial to make a statement here, but enough evidence for MYSELF so that I'm satisfied enough that I can say, "Yes, this is what is helping me, and I've eliminated [list of factors] so I doubt it is anything else".).

    As I write this, I am currently not taking any antibiotics, so I can't state anything about my personal use of them either way.

    CO

    ReplyDelete

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